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Kulkarni AD, Mukarrama T, Barlow BR, Kim J. Recent advances in non-invasive in vivo tracking of cell-based cancer immunotherapies. Biomater Sci 2025; 13:1939-1959. [PMID: 40099377 PMCID: PMC11980607 DOI: 10.1039/d4bm01677g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Abstract
Immunotherapy has been at the forefront of cancer treatment research in recent years due to an increased understanding of the immune system's role in cancer and the substantial benefits it has demonstrated compared to conventional treatment methods. In particular, immune cell-based approaches utilizing T cells, natural killer (NK) cells, macrophages, and more have shown great potential as cancer treatments. While these treatments hold promise, there are still numerous issues that limit their clinical translation, including a lack of understanding of their mechanisms and inconsistent responses to treatment. Traditionally, tissue or blood samples are collected as a means of monitoring treatment progression. However, these in vitro diagnostics are invasive and provide limited information about the real-time status of the treatment or its long-term effectiveness. To address these limitations, novel non-invasive imaging modalities have been developed. These include optical imaging, X-ray computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and single-photon emission computed tomography (SPECT), and photoacoustic (PA) imaging. This review focuses on methods for tracking cell-based cancer immunotherapies using these in vivo imaging modalities, thereby enhancing real-time monitoring of their therapeutic effect and predictions of their long-term efficacy.
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Affiliation(s)
- Anika D Kulkarni
- Department of Biomedical Engineering, University of California, Davis, Davis, 95616, USA.
| | - Tasneem Mukarrama
- Department of Surgery, School of Medicine, University of California, Davis, Sacramento, 95817, USA
| | - Brendan R Barlow
- Department of Surgery, School of Medicine, University of California, Davis, Sacramento, 95817, USA
| | - Jinhwan Kim
- Department of Biomedical Engineering, University of California, Davis, Davis, 95616, USA.
- Department of Surgery, School of Medicine, University of California, Davis, Sacramento, 95817, USA
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2
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Huang Y, Stankevych M, Gujrati V, Klemm U, Mohammed A, Wiesner D, Saccomano M, Tost M, Feuchtinger A, Mishra K, Bruns O, Geerlof A, Ntziachristos V, Stiel AC. Photoswitching protein-XTEN fusions as injectable optoacoustic probes. Acta Biomater 2025; 195:536-546. [PMID: 39914636 DOI: 10.1016/j.actbio.2025.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 01/20/2025] [Accepted: 02/03/2025] [Indexed: 02/11/2025]
Abstract
Optoacoustic imaging (OAI) is a unique in vivo imaging technique combining deep tissue penetration with high resolution and molecular sensitivity. OAI relying on strong intrinsic contrast, such as blood hemoglobin, already shows its value in medical diagnostics. However, OAI sensitivity to current extrinsic contrast agents is insufficient and limits its role in detecting disease-related biomarkers. The recently introduced concept of photoswitching and temporal unmixing techniques for OAI allows detecting extrinsic contrast with high sensitivity, allowing the visualization of small populations of cells labeled with photoswitching proteins deep within the tissue. However, transgene modification might not be permitted in some cases, such as for diagnostic use. Therefore, it is desirable to leverage the concept of photoswitching OAI towards injectable formulations. Since photoswitchable synthetic dyes are mainly excited by blue wavelengths unsuited for imaging in tissue, we propose exploiting the addition of XTENs to photoswitching proteins towards yielding injectable agents. The addition of XTEN to a protein enhances its plasma half-life and bioavailability, thus allowing its use, for example, in targeted labeling approaches. In this pilot study, we show that intravenously injected near-infrared absorbing photoswitchable proteins, ReBphP-PCM, coupled to XTEN, allow highly sensitive optoacoustic visualization of a tumor xenograft in vivo. The sensitivity to XTENs-ReBphP-PCM determined by ex vivo analysis of labeled cells is one to two orders of magnitude beyond conventional synthetic dyes used currently in OAI. The enhanced sensitivity afforded by photoswitching OAI, in combination with the increased bioavailability and biocompatibility of XTENs-ReBphP-PCM, makes this fusion protein a promising tool for facilitating sensitive detection of biomarkers in OAI with a potential for future use in diagnostics. STATEMENT OF SIGNIFICANCE: Optoacoustic imaging (OAI) is a unique in vivo imaging technique that combines deep tissue penetration with high resolution. OAI, which relies on intrinsic contrast, such as blood hemoglobin, could already be valuable in medical diagnostics. However, the use of extrinsic contrast agents to augment disease-related biomarkers in research and diagnostics suffers from very limited sensitivity of the generated contrast agent. We present an intravenously injected photoswitchable protein, ReBphP-PCM, coupled to XTEN, allowing highly sensitive OAI. The sensitivity is one to two orders of magnitude greater than that of conventional synthetic dyes used currently in OA imaging. The high sensitivity afforded by photoswitching together with the enhanced bioavailability and biocompatibility of the XTENs-ReBphP-PCM make this a standard agent for high-quality detection of OAI with potential for clinical use.
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Affiliation(s)
- Yishu Huang
- Institute of Biological and Medical Imaging, Bioengineering Center, Helmholtz Zentrum München, Neuherberg, Germany; Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of Munich, Munich, Germany
| | - Mariia Stankevych
- Institute of Biological and Medical Imaging, Bioengineering Center, Helmholtz Zentrum München, Neuherberg, Germany; Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of Munich, Munich, Germany
| | - Vipul Gujrati
- Institute of Biological and Medical Imaging, Bioengineering Center, Helmholtz Zentrum München, Neuherberg, Germany; Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of Munich, Munich, Germany
| | - Uwe Klemm
- Institute of Biological and Medical Imaging, Bioengineering Center, Helmholtz Zentrum München, Neuherberg, Germany; Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of Munich, Munich, Germany
| | - Azeem Mohammed
- Institute of Biological and Medical Imaging, Bioengineering Center, Helmholtz Zentrum München, Neuherberg, Germany; Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of Munich, Munich, Germany
| | - David Wiesner
- Institute of Biological and Medical Imaging, Bioengineering Center, Helmholtz Zentrum München, Neuherberg, Germany
| | - Mara Saccomano
- Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany
| | - Monica Tost
- Core Facility Pathology & Tissue Analytics, Helmholtz Zentrum München, Neuherberg, Germany
| | - Annette Feuchtinger
- Core Facility Pathology & Tissue Analytics, Helmholtz Zentrum München, Neuherberg, Germany
| | - Kanuj Mishra
- Institute of Biological and Medical Imaging, Bioengineering Center, Helmholtz Zentrum München, Neuherberg, Germany; Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of Munich, Munich, Germany.
| | - Oliver Bruns
- Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany
| | - Arie Geerlof
- Protein Expression and Purification Facility, Institute of Structural Biology, Helmholtz Center Munich for Environmental Health, Neuherberg, Germany
| | - Vasilis Ntziachristos
- Institute of Biological and Medical Imaging, Bioengineering Center, Helmholtz Zentrum München, Neuherberg, Germany; Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of Munich, Munich, Germany
| | - Andre C Stiel
- Institute of Biological and Medical Imaging, Bioengineering Center, Helmholtz Zentrum München, Neuherberg, Germany; Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of Munich, Munich, Germany; Protein Engineering for Superresolution Microscopy Lab, University of Regensburg, Regensburg, Germany.
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Ma J, Li Y, Ying Y, Wu B, Liu Y, Zhou J, Hu L. Progress of Mesoporous Silica Coated Gold Nanorods for Biological Imaging and Cancer Therapy. ChemMedChem 2024; 19:e202300374. [PMID: 37990850 DOI: 10.1002/cmdc.202300374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 11/19/2023] [Accepted: 11/19/2023] [Indexed: 11/23/2023]
Abstract
For unique surface plasmon absorption and fluorescence characteristics, gold nanorods have been developed and widely employed in the biomedical field. However, limitations still exist due their low specific surface area, instability and tendency agglomerate in cytoplasm. Mesoporous silica materials have been broadly applied in field of catalysts, adsorbents, nanoreactors, and drug carriers due to its unique mesoporous structure, highly comparative surface area, good stability and biocompatibility. Therefore, coating gold nanorods with a dendritic mesopore channels can effectively prevent particle agglomeration, while increasing the specific surface area and drug loading efficiency. This review discusses the advancements of GNR@MSN in synthetic process, bio-imaging technique and tumor therapy. Additionally, the further application of GNR@MSN in imaging-guided treatment modalities is explored, while its promising superior application prospect is highlighted. Finally, the issues related to in vivo studies are critically examined for facilitating the transition of this promising nanoplatform into clinical trials.
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Affiliation(s)
- Jiaying Ma
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, University of South China, Hengyang, 421001, PR China
| | - Yongzhen Li
- Department of Pharmacy, School of Pharmacy, University of South China, Hengyang, 421001, PR China
| | - Yunfei Ying
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, University of South China, Hengyang, 421001, PR China
| | - Baibei Wu
- Department of Clinical Medicine, University of South China, Hengyang, 421001, PR China
| | - Yanmei Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, University of South China, Hengyang, 421001, PR China
| | - Juan Zhou
- School of Mechanical Engineering, University of South China, Hengyang, 421001, PR China
| | - Lidan Hu
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, University of South China, Hengyang, 421001, PR China
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Choi W, Park B, Choi S, Oh D, Kim J, Kim C. Recent Advances in Contrast-Enhanced Photoacoustic Imaging: Overcoming the Physical and Practical Challenges. Chem Rev 2023. [PMID: 36642892 DOI: 10.1021/acs.chemrev.2c00627] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
For decades now, photoacoustic imaging (PAI) has been investigated to realize its potential as a niche biomedical imaging modality. Despite its highly desirable optical contrast and ultrasonic spatiotemporal resolution, PAI is challenged by such physical limitations as a low signal-to-noise ratio (SNR), diminished image contrast due to strong optical attenuation, and a lower-bound on spatial resolution in deep tissue. In addition, contrast-enhanced PAI has faced practical limitations such as insufficient cell-specific targeting due to low delivery efficiency and difficulties in developing clinically translatable agents. Identifying these limitations is essential to the continuing expansion of the field, and substantial advances in developing contrast-enhancing agents, complemented by high-performance image acquisition systems, have synergistically dealt with the challenges of conventional PAI. This review covers the past four years of research on pushing the physical and practical challenges of PAI in terms of SNR/contrast, spatial resolution, targeted delivery, and clinical application. Promising strategies for dealing with each challenge are reviewed in detail, and future research directions for next generation contrast-enhanced PAI are discussed.
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Affiliation(s)
- Wonseok Choi
- Department of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, Graduate School of Artificial Intelligence, and Medical Device Innovation Center, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang37673, Republic of Korea
| | - Byullee Park
- Department of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, Graduate School of Artificial Intelligence, and Medical Device Innovation Center, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang37673, Republic of Korea
| | - Seongwook Choi
- Department of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, Graduate School of Artificial Intelligence, and Medical Device Innovation Center, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang37673, Republic of Korea
| | - Donghyeon Oh
- Department of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, Graduate School of Artificial Intelligence, and Medical Device Innovation Center, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang37673, Republic of Korea
| | - Jongbeom Kim
- Department of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, Graduate School of Artificial Intelligence, and Medical Device Innovation Center, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang37673, Republic of Korea
| | - Chulhong Kim
- Department of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, Graduate School of Artificial Intelligence, and Medical Device Innovation Center, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang37673, Republic of Korea
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Nguyen A, Kumar S, Kulkarni AA. Nanotheranostic Strategies for Cancer Immunotherapy. SMALL METHODS 2022; 6:e2200718. [PMID: 36382571 PMCID: PMC11056828 DOI: 10.1002/smtd.202200718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 09/13/2022] [Indexed: 06/16/2023]
Abstract
Despite advancements in cancer immunotherapy, heterogeneity in tumor response impose barriers to successful treatments and accurate prognosis. Effective therapy and early outcome detection are critical as toxicity profiles following immunotherapies can severely affect patients' quality of life. Existing imaging techniques, including positron emission tomography, computed tomography, magnetic resonance imaging, or multiplexed imaging, are often used in clinics yet suffer from limitations in the early assessment of immune response. Conventional strategies to validate immune response mainly rely on the Response Evaluation Criteria in Solid Tumors (RECIST) and the modified iRECIST for immuno-oncology drug trials. However, accurate monitoring of immunotherapy efficacy is challenging since the response does not always follow conventional RECIST criteria due to delayed and variable kinetics in immunotherapy responses. Engineered nanomaterials for immunotherapy applications have significantly contributed to overcoming these challenges by improving drug delivery and dynamic imaging techniques. This review summarizes challenges in recent immune-modulation approaches and traditional imaging tools, followed by emerging developments in three-in-one nanoimmunotheranostic systems co-opting nanotechnology, immunotherapy, and imaging. In addition, a comprehensive overview of imaging modalities in recent cancer immunotherapy research and a brief outlook on how nanotheranostic platforms can potentially advance to clinical translations for the field of immuno-oncology is presented.
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Affiliation(s)
- Anh Nguyen
- Department of Chemical Engineering, University of Massachusetts, Amherst, MA, USA
| | - Sahana Kumar
- Department of Chemical Engineering, University of Massachusetts, Amherst, MA, USA
| | - Ashish A. Kulkarni
- Department of Chemical Engineering, University of Massachusetts, Amherst, MA, USA
- Center for Bioactive Delivery, Institute for Applied Life Sciences, University of Massachusetts, Amherst, MA, USA
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Hui X, Malik MOA, Pramanik M. Looking deep inside tissue with photoacoustic molecular probes: a review. JOURNAL OF BIOMEDICAL OPTICS 2022; 27:070901. [PMID: 36451698 PMCID: PMC9307281 DOI: 10.1117/1.jbo.27.7.070901] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 07/01/2022] [Indexed: 05/19/2023]
Abstract
Significance Deep tissue noninvasive high-resolution imaging with light is challenging due to the high degree of light absorption and scattering in biological tissue. Photoacoustic imaging (PAI) can overcome some of the challenges of pure optical or ultrasound imaging to provide high-resolution deep tissue imaging. However, label-free PAI signals from light absorbing chromophores within the tissue are nonspecific. The use of exogeneous contrast agents (probes) not only enhances the imaging contrast (and imaging depth) but also increases the specificity of PAI by binding only to targeted molecules and often providing signals distinct from the background. Aim We aim to review the current development and future progression of photoacoustic molecular probes/contrast agents. Approach First, PAI and the need for using contrast agents are briefly introduced. Then, the recent development of contrast agents in terms of materials used to construct them is discussed. Then, various probes are discussed based on targeting mechanisms, in vivo molecular imaging applications, multimodal uses, and use in theranostic applications. Results Material combinations are being used to develop highly specific contrast agents. In addition to passive accumulation, probes utilizing activation mechanisms show promise for greater controllability. Several probes also enable concurrent multimodal use with fluorescence, ultrasound, Raman, magnetic resonance imaging, and computed tomography. Finally, targeted probes are also shown to aid localized and molecularly specific photo-induced therapy. Conclusions The development of contrast agents provides a promising prospect for increased contrast, higher imaging depth, and molecularly specific information. Of note are agents that allow for controlled activation, explore other optical windows, and enable multimodal use to overcome some of the shortcomings of label-free PAI.
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Affiliation(s)
- Xie Hui
- Nanyang Technological University, School of Chemical and Biomedical Engineering, Singapore
| | - Mohammad O. A. Malik
- Nanyang Technological University, School of Chemical and Biomedical Engineering, Singapore
| | - Manojit Pramanik
- Nanyang Technological University, School of Chemical and Biomedical Engineering, Singapore
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Application of Dual-Enhanced Surface-Enhanced Raman Scattering Probe Technology in the Diagnosis of Tumor Cells in Vitro. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27113582. [PMID: 35684522 PMCID: PMC9182129 DOI: 10.3390/molecules27113582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/29/2022] [Accepted: 05/30/2022] [Indexed: 11/17/2022]
Abstract
With the development of precision medicine, antigen/antibody-targeted therapy has brought great hope to tumor patients; however, the migration of tumor cells, especially a small number of cells flowing into blood or other tissues, remains a clinical challenge. In particular, it is difficult to use functional gold nanomaterials for targeted clinical tumor diagnosis while simultaneously obtaining stable and highly sensitive Raman signals. Therefore, we developed a detection method for functional Au Nanostars (AuNSs) with dual signal enhancement that can specifically track location and obtain high-intensity surface-enhanced Raman scattering (SERS) signals. First, AuNSs with specific optical properties were synthesized and functionalized. The Raman dye 4-mercapto-hydroxybenzoic acid and polyethylene glycol were coupled with the tumor marker, epidermal growth factor receptor, to obtain the targeted SERS probes. In addition, a detection chip was prepared for Raman detection with physical enhancement, exhibiting a 40-times higher signal intensity than that of quartz glass. This study combines physical enhancement and SERS enhancement technologies to achieve dual enhancement, enabling the detection of a highly sensitive and stable Raman signal; this has potential clinical value for antigen/antibody-targeted tumor diagnosis and treatment.
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Wrede P, Degtyaruk O, Kalva SK, Deán-Ben XL, Bozuyuk U, Aghakhani A, Akolpoglu B, Sitti M, Razansky D. Real-time 3D optoacoustic tracking of cell-sized magnetic microrobots circulating in the mouse brain vasculature. SCIENCE ADVANCES 2022; 8:eabm9132. [PMID: 35544570 PMCID: PMC9094653 DOI: 10.1126/sciadv.abm9132] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 03/25/2022] [Indexed: 05/16/2023]
Abstract
Mobile microrobots hold remarkable potential to revolutionize health care by enabling unprecedented active medical interventions and theranostics, such as active cargo delivery and microsurgical manipulations in hard-to-reach body sites. High-resolution imaging and control of cell-sized microrobots in the in vivo vascular system remains an unsolved challenge toward their clinical use. To overcome this limitation, we propose noninvasive real-time detection and tracking of circulating microrobots using optoacoustic imaging. We devised cell-sized nickel-based spherical Janus magnetic microrobots whose near-infrared optoacoustic signature is enhanced via gold conjugation. The 5-, 10-, and 20-μm-diameter microrobots are detected volumetrically both in bloodless ex vivo tissues and under real-life conditions with a strongly light-absorbing blood background. We further demonstrate real-time three-dimensional tracking and magnetic manipulation of the microrobots circulating in murine cerebral vasculature, thus paving the way toward effective and safe operation of cell-sized microrobots in challenging and clinically relevant intravascular environments.
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Affiliation(s)
- Paul Wrede
- Institute of Pharmacology and Toxicology and Institute for Biomedical Engineering, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland
- Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, ETH Zurich, 8093 Zurich, Switzerland
- Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany
| | - Oleksiy Degtyaruk
- Institute of Pharmacology and Toxicology and Institute for Biomedical Engineering, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland
- Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, ETH Zurich, 8093 Zurich, Switzerland
| | - Sandeep Kumar Kalva
- Institute of Pharmacology and Toxicology and Institute for Biomedical Engineering, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland
- Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, ETH Zurich, 8093 Zurich, Switzerland
| | - Xosé Luis Deán-Ben
- Institute of Pharmacology and Toxicology and Institute for Biomedical Engineering, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland
- Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, ETH Zurich, 8093 Zurich, Switzerland
| | - Ugur Bozuyuk
- Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany
| | - Amirreza Aghakhani
- Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany
| | - Birgul Akolpoglu
- Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany
| | - Metin Sitti
- Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, ETH Zurich, 8093 Zurich, Switzerland
- Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany
- School of Medicine and College of Engineering, Koç University, Istanbul 34450, Turkey
| | - Daniel Razansky
- Institute of Pharmacology and Toxicology and Institute for Biomedical Engineering, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland
- Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, ETH Zurich, 8093 Zurich, Switzerland
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Jaiswal N, Halder S, Mahata N, Chanda N. Bi-Functional Gold Nanorod-Protein Conjugates with Biomimetic BSA@Folic Acid Corona for Improved Tumor Targeting and Intracellular Delivery of Therapeutic Proteins in Colon Cancer 3D Spheroids. ACS APPLIED BIO MATERIALS 2022; 5:1476-1488. [PMID: 35285613 DOI: 10.1021/acsabm.1c01216] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Gold nanorods (AuNRs) remain well-developed inorganic nanocarriers of small molecules for a plethora of biomedical and therapeutic applications. However, the delivery of therapeutic proteins using AuNRs with high protein loading capacity (LC), serum stability, excellent target specificity, and minimal off-target protein release is not known. Herein, we report two bi-functional AuNR-protein nanoconjugates, AuNR@EGFP-BSAFA and AuNR@RNaseA-BSAFA, supramolecularly coated with folic acid-modified BSA (BSAFA) acting as biomimetic protein corona to demonstrate targeted cytosolic delivery of enhanced green fluorescent protein (EGFP) and therapeutic ribonuclease A enzyme (RNase A) in their functional forms. AuNR@EGFP-BSAFA and AuNR@RNaseA-BSAFA exhibit high LCs of ∼42 and ∼54%, respectively, increased colloidal stability, and rapid protein release in the presence of biological thiols. As a nanocarrier, AuNR@EGFP-BSAFA and AuNR@RNaseA-BSAFA show resistance to corona formation in high-serum media even after 24 h, guaranteeing a greater circulation lifetime. Folate receptor-targeting BSAFA on the AuNR surface facilitates the receptor-mediated internalization, followed by the release of EGFP and RNase A in HT29 cells. The green fluorescence dispersed throughout the cell's cytoplasm indicates successful cytosolic delivery of EGFP by AuNR@EGFP-BSAFA. AuNR@RNaseA-BSAFA-mediated therapeutic RNase A delivery in multicellular 3D spheroids of HT29 cells exhibits a radical reduction in the cellular RNA fluorescence intensity to 38%, signifying RNA degradation and subsequent cell death. The versatile nanoformulation strategy in terms of the anisotropic particle morphology, protein type, and ability for targeted delivery in the functional form makes the present AuNR-protein nanoconjugates a promising platform for potential application in cancer management.
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Affiliation(s)
- Namita Jaiswal
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur 713209, India.,Material Processing and Microsystem Laboratory, CSIR─Central Mechanical Engineering Research Institute, Durgapur 713209, India
| | - Sudeshna Halder
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur 713209, India
| | - Nibedita Mahata
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur 713209, India
| | - Nripen Chanda
- Material Processing and Microsystem Laboratory, CSIR─Central Mechanical Engineering Research Institute, Durgapur 713209, India
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Zhao Z, Swartchick CB, Chan J. Targeted contrast agents and activatable probes for photoacoustic imaging of cancer. Chem Soc Rev 2022; 51:829-868. [PMID: 35094040 PMCID: PMC9549347 DOI: 10.1039/d0cs00771d] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Photoacoustic (PA) imaging has emerged as a powerful technique for the high resolution visualization of biological processes within deep tissue. Through the development and application of exogenous targeted contrast agents and activatable probes that can respond to a given cancer biomarker, researchers can image molecular events in vivo during cancer progression. This information can provide valuable details that can facilitate cancer diagnosis and therapy monitoring. In this tutorial review, we provide a step-by-step guide to select a cancer biomarker and subsequent approaches to design imaging agents for in vivo use. We envision this information will be a useful summary to those in the field, new members to the community, and graduate students taking advanced imaging coursework. We also highlight notable examples from the recent literature, with emphasis on the molecular designs and their in vivo PA imaging performance. To conclude, we provide our outlook and future perspective in this exciting field.
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Affiliation(s)
- Zhenxiang Zhao
- Department of Chemistry, Beckman Institute for Advanced Science and Technology, and Cancer Center at Illinois, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois, USA.
| | - Chelsea B Swartchick
- Department of Chemistry, Beckman Institute for Advanced Science and Technology, and Cancer Center at Illinois, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois, USA.
| | - Jefferson Chan
- Department of Chemistry, Beckman Institute for Advanced Science and Technology, and Cancer Center at Illinois, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois, USA.
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Mueller CG, Gaiddon C, Venkatasamy A. Current Clinical and Pre-Clinical Imaging Approaches to Study the Cancer-Associated Immune System. Front Immunol 2021; 12:716860. [PMID: 34539653 PMCID: PMC8446654 DOI: 10.3389/fimmu.2021.716860] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 08/16/2021] [Indexed: 02/01/2023] Open
Abstract
In the light of the success and the expected growth of its arsenal, immuno-therapy may become the standard neoadjuvant procedure for many cancers in the near future. However, aspects such as the identity, organization and the activation status of the peri- and intra-tumoral immune cells would represent important elements to weigh in the decision for the appropriate treatment. While important progress in non-invasive imaging of immune cells has been made over the last decades, it falls yet short of entering the clinics, let alone becoming a standard procedure. Here, we provide an overview of the different intra-vital imaging approaches in the clinics and in pre-clinical settings and discuss their benefits and drawbacks for assessing the activity of the immune system, globally and on a cellular level. Stimulated by further research, the future is likely to see many technological advances both on signal detection and emission as well as image specificity and resolution to tackle current hurdles. We anticipate that the ability to precisely determine an immune stage of cancer will capture the attention of the oncologist and will create a change in paradigm for cancer therapy.
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Affiliation(s)
- Christopher G Mueller
- CNRS UPR 3572, University of Strasbourg, Immunologie-Immunopathologie-Chimie Thérapeutique, Strasbourg, France
| | - Christian Gaiddon
- Inserm UMR_S 1113, University of Strasbourg, Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC), Strasbourg, France
| | - Aïna Venkatasamy
- Inserm UMR_S 1113, University of Strasbourg, Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC), Strasbourg, France.,IHU-Strasbourg (Institut Hospitalo-Universitaire), Strasbourg, France
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12
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Lee JW, Choi SR, Heo JH. Simultaneous Stabilization and Functionalization of Gold Nanoparticles via Biomolecule Conjugation: Progress and Perspectives. ACS APPLIED MATERIALS & INTERFACES 2021; 13:42311-42328. [PMID: 34464527 DOI: 10.1021/acsami.1c10436] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
Gold nanoparticles (AuNPs) are used in various biological applications because of their small surface area-to-volume ratios, ease of synthesis and modification, low toxicity, and unique optical properties. These properties can vary significantly with changes in AuNP size, shape, composition, and arrangement. Thus, the stabilization of AuNPs is crucial to preserve the properties required for biological applications. In recent years, various polymer-based physical and chemical methods have been extensively used for AuNP stabilization. However, a new stabilization approach using biomolecules has recently attracted considerable attention. Biomolecules such as DNA, RNA, peptides, and proteins are representative of the biomoieties that can functionalize AuNPs. According to several studies, biomolecules can stabilize AuNPs in biological media; in addition, AuNP-conjugated biomolecules can retain certain biological functions. Furthermore, the presence of biomolecules on AuNPs significantly enhances their biocompatibility. This review provides a representative overview of AuNP functionalization using various biomolecules. The strategies and mechanisms of AuNP functionalization using biomolecules are comprehensively discussed in the context of various biological fields.
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Affiliation(s)
- Jin Woong Lee
- School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
| | - Seok-Ryul Choi
- School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
| | - Jun Hyuk Heo
- School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
- Advanced Materials Technology Research Center, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
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13
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Gellini C, Feis A. Optothermal properties of plasmonic inorganic nanoparticles for photoacoustic applications. PHOTOACOUSTICS 2021; 23:100281. [PMID: 34194975 PMCID: PMC8233228 DOI: 10.1016/j.pacs.2021.100281] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 05/05/2021] [Accepted: 06/10/2021] [Indexed: 05/08/2023]
Abstract
Plasmonic systems are becoming a favourable alternative to dye molecules in the generation of photoacoustic signals for spectroscopy and imaging. In particular, inorganic nanoparticles are appealing because of their versatility. In fact, as the shape, size and chemical composition of nanoparticles are directly correlated with their plasmonic properties, the excitation wavelength can be tuned to their plasmon resonance by adjusting such traits. This feature enables an extensive spectral range to be covered. In addition, surface chemical modifications can be performed to provide the nanoparticles with designed functionalities, e.g., selective affinity for specific macromolecules. The efficiency of the conversion of absorbed photon energy into heat, which is the physical basis of the photoacoustic signal, can be accurately determined by photoacoustic methods. This review contrasts studies that evaluate photoconversion in various kinds of nanomaterials by different methods, with the objective of facilitating the researchers' choice of suitable plasmonic nanoparticles for photoacoustic applications.
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Affiliation(s)
- Cristina Gellini
- Dipartimento di Chimica “Ugo Schiff”, Università di Firenze, Via della Lastruccia 3, I-50019 Sesto Fiorentino (FI), Italy
| | - Alessandro Feis
- Dipartimento di Chimica “Ugo Schiff”, Università di Firenze, Via della Lastruccia 3, I-50019 Sesto Fiorentino (FI), Italy
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14
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Cui D, Shi Y, Xing D, Yang S. Ultrahigh Sensitive and Tumor-Specific Photoacoustography in NIR-II Region: Optical Writing and Redox-Responsive Graphic Fixing by AgBr@PLGA Nanocrystals. NANO LETTERS 2021; 21:6914-6922. [PMID: 34428906 DOI: 10.1021/acs.nanolett.1c02078] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
The highly up-regulated glutathione (GSH) concentration in the tumor microenvironment is generally identified to be an effective endogenous characteristic of cancerous tissues. Herein, an ultrahigh-sensitive and tumor-specific photoacoustography technique in the near-infrared (NIR-II) region based on optical writing and redox-responsive chromogenic graphic fixing is developed by introducing a self-synthesized photosensitive silver bromide modified with poly lactic-co-glycolic acid (AgBr@PLGA) nanocrystals. After they are optically triggered by external light, the NIR-transparent AgBr@PLGA nanocrystals can be reduced by the tumor-abundant GSH into strongly absorbing silver nanoparticles, significantly boosting the "turn-on" photoacoustic (PA) signal in the NIR-II region; therefore, the tumor area can be graphically fixed and developed in the photoacoustography. Experiments on both in vitro phantoms and in vivo mouse models demonstrate that the tumor area is specifically identified by the photoacoustography with the background signals effectively suppressed by dynamically modulating the exposure time. The tumor-specific photoacoustography technique prefigures great potential for high-precision cancer diagnosis and treatment monitoring.
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Affiliation(s)
- Dandan Cui
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
| | - Yujiao Shi
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
| | - Da Xing
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
| | - Sihua Yang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
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15
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Albrecht W, Arslan Irmak E, Altantzis T, Pedrazo-Tardajos A, Skorikov A, Deng TS, van der Hoeven JES, van Blaaderen A, Van Aert S, Bals S. 3D Atomic-Scale Dynamics of Laser-Light-Induced Restructuring of Nanoparticles Unraveled by Electron Tomography. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2021; 33:e2100972. [PMID: 34247423 DOI: 10.1002/adma.202100972] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 04/15/2021] [Indexed: 06/13/2023]
Abstract
Understanding light-matter interactions in nanomaterials is crucial for optoelectronic, photonic, and plasmonic applications. Specifically, metal nanoparticles (NPs) strongly interact with light and can undergo shape transformations, fragmentation and ablation upon (pulsed) laser excitation. Despite being vital for technological applications, experimental insight into the underlying atomistic processes is still lacking due to the complexity of such measurements. Herein, atomic resolution electron tomography is performed on the same mesoporous-silica-coated gold nanorod, before and after femtosecond laser irradiation, to assess the missing information. Combined with molecular dynamics (MD) simulations based on the experimentally determined 3D atomic-scale morphology, the complex atomistic rearrangements, causing shape deformations and defect generation, are unraveled. These rearrangements are simultaneously driven by surface diffusion, facet restructuring, and strain formation, and are influenced by subtleties in the atomic distribution at the surface.
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Affiliation(s)
- Wiebke Albrecht
- EMAT and NANOlab Center of Excellence, University of Antwerp, Groenenborgerlaan 171, Antwerp, B-2020, Belgium
- Soft Condensed Matter, Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 5, Utrecht, 3584 CC, The Netherlands
| | - Ece Arslan Irmak
- EMAT and NANOlab Center of Excellence, University of Antwerp, Groenenborgerlaan 171, Antwerp, B-2020, Belgium
| | - Thomas Altantzis
- EMAT and NANOlab Center of Excellence, University of Antwerp, Groenenborgerlaan 171, Antwerp, B-2020, Belgium
| | - Adrián Pedrazo-Tardajos
- EMAT and NANOlab Center of Excellence, University of Antwerp, Groenenborgerlaan 171, Antwerp, B-2020, Belgium
| | - Alexander Skorikov
- EMAT and NANOlab Center of Excellence, University of Antwerp, Groenenborgerlaan 171, Antwerp, B-2020, Belgium
| | - Tian-Song Deng
- School of Electronics and Information Engineering, Hangzhou Dianzi University, No. 1158, 2nd Avenue, Baiyang Street, Hangzhou, 310018, China
| | - Jessi E S van der Hoeven
- Soft Condensed Matter, Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 5, Utrecht, 3584 CC, The Netherlands
| | - Alfons van Blaaderen
- Soft Condensed Matter, Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 5, Utrecht, 3584 CC, The Netherlands
| | - Sandra Van Aert
- EMAT and NANOlab Center of Excellence, University of Antwerp, Groenenborgerlaan 171, Antwerp, B-2020, Belgium
| | - Sara Bals
- EMAT and NANOlab Center of Excellence, University of Antwerp, Groenenborgerlaan 171, Antwerp, B-2020, Belgium
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16
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Khan NU, Lin J, Younas MR, Liu X, Shen L. Synthesis of gold nanorods and their performance in the field of cancer cell imaging and photothermal therapy. Cancer Nanotechnol 2021. [DOI: 10.1186/s12645-021-00092-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
AbstractCancer is one of the most common incident in the world, with malignant tumors having a death rate of up to 19%. A new method of treating cancer cells effectively with minimal cytotoxicity is needed. In the field of biomedicine with unique shape-dependent optical properties, gold nanorods (GNRs) have attracted worldwide interest. These nanorods have two distinct plasmon bands. One is transverse plasmon band in the area of visible light, and the other is longitudinal band of plasmons in near infrared region. These specific characters provide promise for the design of new optically active reagents that simultaneously perform light-mediated imaging and photothermal cancer treatment. We begin our review by summarizing the latest developments in gold nanorods synthesis with a focus on seed-mediated growth method. Nanorods spontaneous self-assembly, polymer-based alignment and its applications as a novel agent for simultaneous bioimaging and photothermal cancer therapy are listed in particular.
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17
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Abstract
Photoacoustic tomography (PAT) that integrates the molecular contrast of optical imaging with the high spatial resolution of ultrasound imaging in deep tissue has widespread applications in basic biological science, preclinical research, and clinical trials. Recently, tremendous progress has been made in PAT regarding technical innovations, preclinical applications, and clinical translations. Here, we selectively review the recent progresses and advances in PAT, including the development of advanced PAT systems for small-animal and human imaging, newly engineered optical probes for molecular imaging, broad-spectrum PAT for label-free imaging of biological tissues, high-throughput snapshot photoacoustic topography, and integration of machine learning for image reconstruction and processing. We envision that PAT will have further technical developments and more impactful applications in biomedicine.
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Affiliation(s)
- Lei Li
- Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, 1200 East California Boulevard, Mail Code 138-78, Pasadena, CA 91125, USA
| | - Lihong V. Wang
- Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, 1200 East California Boulevard, Mail Code 138-78, Pasadena, CA 91125, USA
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18
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Zhang K, Sun Y, Wu S, Zhou M, Zhang X, Zhou R, Zhang T, Gao Y, Chen T, Chen Y, Yao X, Watanabe Y, Tian M, Zhang H. Systematic imaging in medicine: a comprehensive review. Eur J Nucl Med Mol Imaging 2021; 48:1736-1758. [PMID: 33210241 DOI: 10.1007/s00259-020-05107-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 11/08/2020] [Indexed: 01/05/2023]
Abstract
Systematic imaging can be broadly defined as the systematic identification and characterization of biological processes at multiple scales and levels. In contrast to "classical" diagnostic imaging, systematic imaging emphasizes on detecting the overall abnormalities including molecular, functional, and structural alterations occurring during disease course in a systematic manner, rather than just one aspect in a partial manner. Concomitant efforts including improvement of imaging instruments, development of novel imaging agents, and advancement of artificial intelligence are warranted for achievement of systematic imaging. It is undeniable that scientists and radiologists will play a predominant role in directing this burgeoning field. This article introduces several recent developments in imaging modalities and nanoparticles-based imaging agents, and discusses how systematic imaging can be achieved. In the near future, systematic imaging which combines multiple imaging modalities with multimodal imaging agents will pave a new avenue for comprehensive characterization of diseases, successful achievement of image-guided therapy, precise evaluation of therapeutic effects, and rapid development of novel pharmaceuticals, with the final goal of improving human health-related outcomes.
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Affiliation(s)
- Kai Zhang
- Department of Nuclear Medicine and PET center, The Second Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
- Laboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan
| | - Yujie Sun
- State Key Laboratory of Membrane Biology, Biodynamic Optical Imaging Center, School of Life Sciences, Peking University, Beijing, China
| | - Shuang Wu
- Department of Nuclear Medicine and PET center, The Second Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Min Zhou
- Department of Nuclear Medicine and PET center, The Second Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
- Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaohui Zhang
- Department of Nuclear Medicine and PET center, The Second Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Rui Zhou
- Department of Nuclear Medicine and PET center, The Second Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Tingting Zhang
- Department of Nuclear Medicine and PET center, The Second Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Yuanxue Gao
- Department of Nuclear Medicine and PET center, The Second Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Ting Chen
- Department of Nuclear Medicine and PET center, The Second Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Yao Chen
- Department of Nuclear Medicine and PET center, The Second Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Xin Yao
- Department of Gastroenterology, The First Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yasuyoshi Watanabe
- Laboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
| | - Mei Tian
- Department of Nuclear Medicine and PET center, The Second Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
| | - Hong Zhang
- Department of Nuclear Medicine and PET center, The Second Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
- Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, China.
- The College of Biomedical Engineering and Instrument Science of Zhejiang University, Hangzhou, China.
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19
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Si P, Razmi N, Nur O, Solanki S, Pandey CM, Gupta RK, Malhotra BD, Willander M, de la Zerda A. Gold nanomaterials for optical biosensing and bioimaging. NANOSCALE ADVANCES 2021; 3:2679-2698. [PMID: 36134176 PMCID: PMC9418567 DOI: 10.1039/d0na00961j] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 03/12/2021] [Indexed: 05/03/2023]
Abstract
Gold nanoparticles (AuNPs) are highly compelling nanomaterials for biomedical studies due to their unique optical properties. By leveraging the versatile optical properties of different gold nanostructures, the performance of biosensing and biomedical imaging can be dramatically improved in terms of their sensitivity, specificity, speed, contrast, resolution and penetration depth. Here we review recent advances of optical biosensing and bioimaging techniques based on three major optical properties of AuNPs: surface plasmon resonance, surface enhanced Raman scattering and luminescence. We summarize the fabrication methods and optical properties of different types of AuNPs, highlight the emerging applications of these AuNPs for novel optical biosensors and biomedical imaging innovations, and discuss the future trends of AuNP-based optical biosensors and bioimaging as well as the challenges of implementing these techniques in preclinical and clinical investigations.
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Affiliation(s)
- Peng Si
- Department of Structural Biology, Stanford University California 94305 USA
| | - Nasrin Razmi
- Department of Science and Technology, Physics and Electronics, Linköping University SE-60174 Norrköping Sweden
| | - Omer Nur
- Department of Science and Technology, Physics and Electronics, Linköping University SE-60174 Norrköping Sweden
| | - Shipra Solanki
- Department of Biotechnology, Delhi Technological University Shahbad Daulatpur Delhi 110042 India
- Department of Applied Chemistry, Delhi Technological University Shahbad Daulatpur Delhi 110042 India
| | - Chandra Mouli Pandey
- Department of Applied Chemistry, Delhi Technological University Shahbad Daulatpur Delhi 110042 India
| | - Rajinder K Gupta
- Department of Applied Chemistry, Delhi Technological University Shahbad Daulatpur Delhi 110042 India
| | - Bansi D Malhotra
- Department of Biotechnology, Delhi Technological University Shahbad Daulatpur Delhi 110042 India
| | - Magnus Willander
- Department of Science and Technology, Physics and Electronics, Linköping University SE-60174 Norrköping Sweden
| | - Adam de la Zerda
- Department of Structural Biology, Stanford University California 94305 USA
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20
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Li S, Lui KH, Li X, Fang X, Lo WS, Gu YJ, Wong WT. pH-Triggered Poly(ethylene glycol)–Poly(lactic acid/glycolic acid)/Croconaine Nanoparticles-Assisted Multiplexed Photoacoustic Imaging and Enhanced Photothermal Cancer Therapy. ACS APPLIED BIO MATERIALS 2021; 4:4152-4164. [DOI: 10.1021/acsabm.0c01578] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Shiying Li
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Kwok-Ho Lui
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Xin Li
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Xueyang Fang
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Wai-Sum Lo
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Yan-Juan Gu
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Wing-Tak Wong
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
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21
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Photoacoustic Molecular Imaging: Principles and Practice. Mol Imaging 2021. [DOI: 10.1016/b978-0-12-816386-3.00016-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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22
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Yang JM, Ghim CM. Photoacoustic Tomography Opening New Paradigms in Biomedical Imaging. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1310:239-341. [PMID: 33834440 DOI: 10.1007/978-981-33-6064-8_11] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
After the emergence of the ultrasound, X-ray CT, PET, and MRI, photoacoustic tomography (PAT) is now in the phase of its exponential growth, with its expected full maturation being another form of mainstream clinical imaging modality. By combining the high contrast benefit of optical imaging and the high-resolution deep imaging capability of ultrasound, PAT can provide unprecedented anatomical image contrasts at clinically relevant depths as well as enable the use of a variety of functional and molecular imaging information, which is not possible with conventional imaging modalities. With these strengths, PAT has achieved numerous breakthroughs in various biomedical applications and also provided new technical platforms that may be able to resolve unmet issues in clinics. In this chapter, we provide an overview of the development of PAT technology for several major biomedical applications and provide an approximate projection of the future of PAT.
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Affiliation(s)
- Joon-Mo Yang
- Center for Photoacoustic Medical Instruments, Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
| | - Cheol-Min Ghim
- Department of Physics, School of Natural Science, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea
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23
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D’Hollander A, Vande Velde G, Jans H, Vanspauwen B, Vermeersch E, Jose J, Struys T, Stakenborg T, Lagae L, Himmelreich U. Assessment of the Theranostic Potential of Gold Nanostars-A Multimodal Imaging and Photothermal Treatment Study. NANOMATERIALS 2020; 10:nano10112112. [PMID: 33114177 PMCID: PMC7690792 DOI: 10.3390/nano10112112] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/19/2020] [Accepted: 10/21/2020] [Indexed: 12/13/2022]
Abstract
Gold nanoparticles offer the possibility to combine both imaging and therapy of otherwise difficult to treat tumors. To validate and further improve their potential, we describe the use of gold nanostars that were functionalized with a polyethyleneglycol-maleimide coating for in vitro and in vivo photoacoustic imaging (PAI), computed tomography (CT), as well as photothermal therapy (PTT) of cancer cells and tumor masses, respectively. Nanostar shaped particles show a high absorption coefficient in the near infrared region and have a hydrodynamic size in biological medium around 100 nm, which allows optimal intra-tumoral retention. Using these nanostars for in vitro labeling of tumor cells, high intracellular nanostar concentrations could be achieved, resulting in high PAI and CT contrast and effective PTT. By injecting the nanostars intratumorally, high contrast could be generated in vivo using PAI and CT, which allowed successful multi-modal tumor imaging. PTT was successfully induced, resulting in tumor cell death and subsequent inhibition of tumor growth. Therefore, gold nanostars are versatile theranostic agents for tumor therapy.
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Affiliation(s)
- Antoine D’Hollander
- Biomedical MRI, Department of Imaging and Pathology, Faculty of Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; (A.D.); (G.V.V.); (E.V.)
- Molecular Small Animal Imaging Center (MoSAIC), KU Leuven, Herestraat 49, 3000 Leuven, Belgium
- Department of Life Science Technology, IMEC, Kapeldreef 75, 3001 Leuven, Belgium; (H.J.); (B.V.); (T.S.); (L.L.)
| | - Greetje Vande Velde
- Biomedical MRI, Department of Imaging and Pathology, Faculty of Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; (A.D.); (G.V.V.); (E.V.)
- Molecular Small Animal Imaging Center (MoSAIC), KU Leuven, Herestraat 49, 3000 Leuven, Belgium
| | - Hilde Jans
- Department of Life Science Technology, IMEC, Kapeldreef 75, 3001 Leuven, Belgium; (H.J.); (B.V.); (T.S.); (L.L.)
| | - Bram Vanspauwen
- Department of Life Science Technology, IMEC, Kapeldreef 75, 3001 Leuven, Belgium; (H.J.); (B.V.); (T.S.); (L.L.)
| | - Elien Vermeersch
- Biomedical MRI, Department of Imaging and Pathology, Faculty of Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; (A.D.); (G.V.V.); (E.V.)
- Molecular Small Animal Imaging Center (MoSAIC), KU Leuven, Herestraat 49, 3000 Leuven, Belgium
| | - Jithin Jose
- Fujifilm Visualsonics, Joop Geesinkweg140, 1114 AB Amsterdam, The Netherlands;
| | - Tom Struys
- Lab of Histology, Biomedical Research Institute, Hasselt University, Agora Laan Gebouw C, 3590 Diepenbeek, Belgium;
| | - Tim Stakenborg
- Department of Life Science Technology, IMEC, Kapeldreef 75, 3001 Leuven, Belgium; (H.J.); (B.V.); (T.S.); (L.L.)
| | - Liesbet Lagae
- Department of Life Science Technology, IMEC, Kapeldreef 75, 3001 Leuven, Belgium; (H.J.); (B.V.); (T.S.); (L.L.)
- Department of Physics, Faculty of Sciences, Laboratory of Soft Matter and Biophysics, KU Leuven, Celestijnenlaan 200D, 3001 Leuven, Belgium
| | - Uwe Himmelreich
- Biomedical MRI, Department of Imaging and Pathology, Faculty of Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; (A.D.); (G.V.V.); (E.V.)
- Molecular Small Animal Imaging Center (MoSAIC), KU Leuven, Herestraat 49, 3000 Leuven, Belgium
- Correspondence: ; Tel.: +32-16-330925
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Xavierselvan M, Singh MKA, Mallidi S. In Vivo Tumor Vascular Imaging with Light Emitting Diode-Based Photoacoustic Imaging System. SENSORS (BASEL, SWITZERLAND) 2020; 20:E4503. [PMID: 32806575 PMCID: PMC7472236 DOI: 10.3390/s20164503] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 08/07/2020] [Accepted: 08/08/2020] [Indexed: 12/13/2022]
Abstract
Photoacoustic (PA) imaging has shown tremendous promise for imaging tumor vasculature and its function at deeper penetration depths without the use of exogenous contrast agents. Traditional PA imaging systems employ expensive and bulky class IV lasers with low pulse repetition rate, due to which its availability for preclinical cancer research is hampered. In this study, we evaluated the capability of a Light-Emitting Diode (LED)-based PA and ultrasound (US) imaging system for monitoring heterogeneous microvasculature in tumors (up to 10 mm in depth) and quantitatively compared the PA images with gold standard histology images. We used a combination of a 7 MHz linear array US transducer and 850 nm excitation wavelength LED arrays to image blood vessels in a subcutaneous tumor model. After imaging, the tumors were sectioned and stained for endothelial cells to correlate with PA images across similar cross-sections. Analysis of 30 regions of interest in tumors from different mice showed a statistically significant R-value of 0.84 where the areas with high blood vessel density had high PA response while low blood vessel density regions had low PA response. Our results confirm that LED-based PA and US imaging can provide 2D and 3D images of tumor vasculature and the potential it has as a valuable tool for preclinical cancer research.
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Affiliation(s)
- Marvin Xavierselvan
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA;
| | - Mithun Kuniyil Ajith Singh
- Research & Business Development Division, Cyberdyne INC, Cambridge Innovation Center, 3013 Rotterdam, The Netherlands;
| | - Srivalleesha Mallidi
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA;
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
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25
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Liu WW, Li PC. Photoacoustic imaging of cells in a three-dimensional microenvironment. J Biomed Sci 2020; 27:3. [PMID: 31948442 PMCID: PMC6966874 DOI: 10.1186/s12929-019-0594-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 11/18/2019] [Indexed: 12/21/2022] Open
Abstract
Imaging live cells in a three-dimensional (3D) culture system yields more accurate information and spatial visualization of the interplay of cells and the surrounding matrix components compared to using a two-dimensional (2D) cell culture system. However, the thickness of 3D cultures results in a high degree of scattering that makes it difficult for the light to penetrate deeply to allow clear optical imaging. Photoacoustic (PA) imaging is a powerful imaging modality that relies on a PA effect generated when light is absorbed by exogenous contrast agents or endogenous molecules in a medium. It combines a high optical contrast with a high acoustic spatiotemporal resolution, allowing the noninvasive visualization of 3D cellular scaffolds at considerable depths with a high resolution and no image distortion. Moreover, advances in targeted contrast agents have also made PA imaging capable of molecular and cellular characterization for use in preclinical personalized diagnostics or PA imaging-guided therapeutics. Here we review the applications and challenges of PA imaging in a 3D cellular microenvironment. Potential future developments of PA imaging in preclinical applications are also discussed.
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Affiliation(s)
- Wei-Wen Liu
- Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan
| | - Pai-Chi Li
- Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
- Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan.
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26
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Chen H, Shi Y, Xing D. Photoacoustic thermorelaxation microscopy for thermal diffusivity measurement. OPTICS LETTERS 2019; 44:3366-3369. [PMID: 31259962 DOI: 10.1364/ol.44.003366] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 06/09/2019] [Indexed: 06/09/2023]
Abstract
Thermal diffusivity is one of the main parameters to characterize the thermo-physical properties of materials, and advances in its measurement technique will have significant impact on materials science and related applications. Here a photoacoustic (PA) thermorelaxation microscopy is proposed as a new noncontact method to measure the thermal diffusivity. By delivering co-focused heating/probing laser pulse pairs with tunable time delays, the sample's in situ thermal relaxation behavior after the heating pulse excitation can be photoacoustically monitored based on the temperature-dependent property of the Grueneisen parameter. We theoretically deduced the dependence of the obtained PA thermorelaxation time on the thermal diffusivity, and the results coincided well with simulations. The feasibility of this method was validated by various industrial and biological samples. This method provides a new strategy for high-resolution thermal diffusivity measurement with flexible measurement conditions, prefiguring great potential for material and biological applications.
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27
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Han S, Bouchard R, Sokolov KV. Molecular photoacoustic imaging with ultra-small gold nanoparticles. BIOMEDICAL OPTICS EXPRESS 2019; 10:3472-3483. [PMID: 31360601 PMCID: PMC6640831 DOI: 10.1364/boe.10.003472] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 06/06/2019] [Accepted: 06/07/2019] [Indexed: 05/14/2023]
Abstract
Gold nanoparticles (AuNPs) below 10 nm in size can undergo renal clearance, which could facilitate their clinical translation. However, due to non-linear, direct relationship between their absorption and size, use of such "ultra-small" AuNPs as contrast agents for photoacoustic imaging (PAI) is challenging. This problem is complicated by the tendency of absorption for ultra-small AuNPs to be below the NIR range, which is optimal for in vivo imaging. Herein, we present 5-nm molecularly activated plasmonic nanosensors (MAPS) that produce a strong photoacoustic signal in labeled cancer cells in the NIR, demonstrating the feasibility of sensitive PAI with ultra-small AuNPs.
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Affiliation(s)
- Sangheon Han
- Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005, USA
- Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
| | - Richard Bouchard
- Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
- The University of Texas MD Anderson Cancer Center Graduate School of Biomedical Sciences, Houston, TX 77030, USA
| | - Konstantin V. Sokolov
- Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005, USA
- Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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28
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Advances in the strategies for designing receptor-targeted molecular imaging probes for cancer research. J Control Release 2019; 305:1-17. [DOI: 10.1016/j.jconrel.2019.04.030] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 04/09/2019] [Accepted: 04/21/2019] [Indexed: 12/24/2022]
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29
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Fales AM, Vogt WC, Wear KA, Ilev IK, Pfefer TJ. Pulsed laser damage of gold nanorods in turbid media and its impact on multi-spectral photoacoustic imaging. BIOMEDICAL OPTICS EXPRESS 2019; 10:1919-1934. [PMID: 31061767 PMCID: PMC6485005 DOI: 10.1364/boe.10.001919] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 02/06/2019] [Accepted: 02/08/2019] [Indexed: 05/03/2023]
Abstract
Innovative biophotonic modalities such as photoacoustic imaging (PAI) have the potential to provide enhanced sensitivity and molecule-specific detection when used with nanoparticles. However, high peak irradiance levels generated by pulsed lasers can lead to modification of plasmonic nanoparticles. Thus, there is an outstanding need to develop practical methods to effectively predict the onset nanoparticle photomodification as well as a need to better understand the process during PAI. To address this need, we studied pulsed laser damage of gold nanorods (GNRs) using turbid phantoms and a multi-spectral near-infrared PAI system, comparing results with spectrophotometric measurements of non-scattering samples. Transmission electron microscopy and Monte Carlo modeling were also performed to elucidate damage processes. In the phantoms, shifts in PAI-detected spectra indicative of GNR damage were initiated at exposure levels one-third of that seen in non-scattering samples, due to turbidity-induced enhancement of subsurface fluence. For exposures approaching established safety limits, damage was detected at depths of up to 12.5 mm. Typically, GNR damage occurred rapidly, over the course of a few laser pulses. This work advances the development of test methods and numerical models as tools for assessment of nanoparticle damage and its implications, and highlights the importance of considering GNR damage in development of PAI products, even for exposures well below laser safety limits.
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Affiliation(s)
- Andrew M. Fales
- Division of Biomedical Physics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA
| | - William C. Vogt
- Division of Biomedical Physics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA
| | - Keith A. Wear
- Division of Applied Mechanics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA
| | - Ilko K. Ilev
- Division of Biomedical Physics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA
| | - T. Joshua Pfefer
- Division of Biomedical Physics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA
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30
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Liu Y, Bhattarai P, Dai Z, Chen X. Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer. Chem Soc Rev 2019; 48:2053-2108. [PMID: 30259015 PMCID: PMC6437026 DOI: 10.1039/c8cs00618k] [Citation(s) in RCA: 1787] [Impact Index Per Article: 297.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The nonradiative conversion of light energy into heat (photothermal therapy, PTT) or sound energy (photoacoustic imaging, PAI) has been intensively investigated for the treatment and diagnosis of cancer, respectively. By taking advantage of nanocarriers, both imaging and therapeutic functions together with enhanced tumour accumulation have been thoroughly studied to improve the pre-clinical efficiency of PAI and PTT. In this review, we first summarize the development of inorganic and organic nano photothermal transduction agents (PTAs) and strategies for improving the PTT outcomes, including applying appropriate laser dosage, guiding the treatment via imaging techniques, developing PTAs with absorption in the second NIR window, increasing photothermal conversion efficiency (PCE), and also increasing the accumulation of PTAs in tumours. Second, we introduce the advantages of combining PTT with other therapies in cancer treatment. Third, the emerging applications of PAI in cancer-related research are exemplified. Finally, the perspectives and challenges of PTT and PAI for combating cancer, especially regarding their clinical translation, are discussed. We believe that PTT and PAI having noteworthy features would become promising next-generation non-invasive cancer theranostic techniques and improve our ability to combat cancers.
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Affiliation(s)
- Yijing Liu
- Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA
| | - Pravin Bhattarai
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
| | - Zhifei Dai
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
| | - Xiaoyuan Chen
- Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA
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31
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Huo D, Kim MJ, Lyu Z, Shi Y, Wiley BJ, Xia Y. One-Dimensional Metal Nanostructures: From Colloidal Syntheses to Applications. Chem Rev 2019; 119:8972-9073. [DOI: 10.1021/acs.chemrev.8b00745] [Citation(s) in RCA: 180] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Da Huo
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United States
| | - Myung Jun Kim
- Department of Chemistry, Duke University, Durham, North Carolina 27708, United States
| | - Zhiheng Lyu
- School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
| | - Yifeng Shi
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
| | - Benjamin J. Wiley
- Department of Chemistry, Duke University, Durham, North Carolina 27708, United States
| | - Younan Xia
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United States
- School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
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32
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Chee RKW, Li Y, Zhang W, Campbell RE, Zemp RJ. In vivo photoacoustic difference-spectra imaging of bacteria using photoswitchable chromoproteins. JOURNAL OF BIOMEDICAL OPTICS 2018; 23:1-11. [PMID: 30334395 DOI: 10.1117/1.jbo.23.10.106006] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Accepted: 09/17/2018] [Indexed: 06/08/2023]
Abstract
Photoacoustic (PA) imaging offers great promise for deep molecular imaging of optical reporters but has difficulties in imaging multiple molecular probes simultaneously in a strong blood background. Photoswitchable chromoproteins like BphP1 have recently allowed for sensitive PA detection by reducing high-blood background signals but lack multiplexing capabilities. We propose a method known as difference-spectra demixing for multiplexing multiple photoswitchable chromoproteins and introduce a second photoswitchable chromoprotein, sGPC2. sGPC2 has a far-red and orange state with peaks at 700 and 630 nm, respectively. It is roughly one-tenth the size of BphP1 and photoswitches four times as fast (2.4% per mJ / cm2). We simultaneously image Escherichia coli expressing sGPC2 and BphP1 injected in mice in vivo. Difference-spectra demixing obtained successful multiplexed images of photoswitchable molecular probes, resulting in a 21.6-fold increase in contrast-to-noise ratio in vivo over traditional PA imaging and an 8% to 40% reduction in erroneously demixed signals in comparison with traditional spectral demixing. PA imaging and characterization were conducted using a custom-built photoswitching PA imaging system.
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Affiliation(s)
- Ryan K W Chee
- University of Alberta, Department of Electrical and Computer Engineering, Edmonton, Canada
| | - Yan Li
- University of Alberta, Department of Chemistry, Edmonton, Canada
| | - Wei Zhang
- University of Alberta, Department of Chemistry, Edmonton, Canada
| | | | - Roger J Zemp
- University of Alberta, Department of Electrical and Computer Engineering, Edmonton, Canada
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33
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Yao J, Wang LV. Recent progress in photoacoustic molecular imaging. Curr Opin Chem Biol 2018; 45:104-112. [PMID: 29631120 PMCID: PMC6076847 DOI: 10.1016/j.cbpa.2018.03.016] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Revised: 03/24/2018] [Accepted: 03/27/2018] [Indexed: 01/08/2023]
Abstract
By acoustically detecting the optical absorption contrast, photoacoustic (PA) tomography (PAT) has broken the penetration limits of traditional high-resolution optical imaging. Through spectroscopic analysis of the target's optical absorption, PAT can identify a wealth of endogenous and exogenous molecules and thus is inherently capable of molecular imaging with high sensitivity. PAT's molecular sensitivity is uniquely accompanied by non-ionizing radiation, high spatial resolution, and deep penetration in biological tissues, which other optical imaging modalities cannot achieve yet. In this concise review, we summarize the most recent technological advancements in PA molecular imaging and highlight the novel molecular probes specifically made for PAT in deep tissues. We conclude with a brief discussion of the opportunities for future advancements.
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Affiliation(s)
- Junjie Yao
- Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
| | - Lihong V Wang
- Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
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34
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A Colorimetric Probe Based on Functionalized Gold Nanorods for Sensitive and Selective Detection of As(III) Ions. SENSORS 2018; 18:s18072372. [PMID: 30037086 PMCID: PMC6069139 DOI: 10.3390/s18072372] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 07/08/2018] [Accepted: 07/17/2018] [Indexed: 02/07/2023]
Abstract
A colorimetric probe for determination of As(III) ions in aqueous solutions on basis of localized surface plasmon resonance (LSPR) was synthesized. The dithiothreitol molecules with two end thiols covalently combined with Au Nanorods (AuNRs) with an aspect ratio of 2.9 by Au-S bond to form dithiothreitol coated Au Nanorods (DTT-AuNRs), acting as colorimetric probe for the determination of As(III) ions. With the adding of As(III) ions, the AuNRs will be aggregated and leading the longitudinal SPR absorption band of DTT-AuNRs decrease due to the As(III) ions can bind with three DTT molecules through an As-S linkage. The potential factors affect the response of DTT-AuNRs to As(III) ions including the concentration of DTT, pH values of DTT-AuNRs, reaction time and NaCl concentration were optimized. Under optimum assay conditions, the DTT-AuNRs colorimetric probe has high sensitivity towards As(III) ions with low detection limit of 38 nM by rules of 3σ/k and excellent linear range of 0.13–10.01 μM. The developed colorimetric probe shows high selectivity for As(III) ions sensing and has applied to determine of As(III) in environmental water samples with quantitative spike-recoveries range from 95.2% to 100.4% with low relative standard deviation of less than 4.4% (n = 3).
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35
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An L, Cox BT. Estimating relative chromophore concentrations from multiwavelength photoacoustic images using independent component analysis. JOURNAL OF BIOMEDICAL OPTICS 2018; 23:1-10. [PMID: 29992796 DOI: 10.1117/1.jbo.23.7.076007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2017] [Accepted: 06/15/2018] [Indexed: 05/07/2023]
Abstract
Independent component analysis (ICA) is an unmixing method based on a linear model. It has previously been applied in in vivo multiwavelength photoacoustic imaging studies to unmix the components representing individual chromophores by assuming that they are statistically independent. Numerically simulated and experimentally acquired two-dimensional images of tissue-mimicking phantoms are used to investigate the conditions required for ICA to give accurate estimates of the relative chromophore concentrations. A simple approximate fluence correction was applied to reduce but not completely remove the nonlinear fluence distortion, as might be possible in practice. The results show that ICA is robust against the residual effect of the partially corrected fluence distortion. ICA is shown to provide accurate unmixing of the chromophores when the absorption coefficient is within a certain range of values, where the upper absorption threshold is comparable to the absorption of blood. When the absorption is increased beyond these thresholds, ICA abruptly fails to unmix the chromophores accurately. The ICA approach was compared to a linear spectroscopic inversion (SI) with known absorption spectra. In cases where the mixing matrix with the specific absorption spectra is ill-conditioned, ICA is able to provide accurate unmixing when SI results in large errors.
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Affiliation(s)
- Lu An
- University College London, Department of Medical Physics and Biomedical Engineering, London, United Kingdom
| | - Benjamin T Cox
- University College London, Department of Medical Physics and Biomedical Engineering, London, United Kingdom
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36
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Photoacoustic microscopy: principles and biomedical applications. Biomed Eng Lett 2018; 8:203-213. [PMID: 30603203 DOI: 10.1007/s13534-018-0067-2] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Revised: 04/12/2018] [Accepted: 04/12/2018] [Indexed: 12/12/2022] Open
Abstract
Photoacoustic microscopy (PAM) has become an increasingly popular technology for biomedical applications, providing anatomical, functional, and molecular information. In this concise review, we first introduce the basic principles and typical system designs of PAM, including optical-resolution PAM and acoustic-resolution PAM. The major imaging characteristics of PAM, i.e. spatial resolutions, penetration depth, and scanning approach are discussed in detail. Then, we introduce the major biomedical applications of PAM, including anatomical imaging across scales from cellular level to organismal level, label-free functional imaging using endogenous biomolecules, and molecular imaging using exogenous contrast agents. Lastly, we discuss the technical and engineering challenges of PAM in the translation to potential clinical impacts.
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37
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Kim H, Beack S, Han S, Shin M, Lee T, Park Y, Kim KS, Yetisen AK, Yun SH, Kwon W, Hahn SK. Multifunctional Photonic Nanomaterials for Diagnostic, Therapeutic, and Theranostic Applications. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2018; 30. [PMID: 29363198 DOI: 10.1002/adma.201701460] [Citation(s) in RCA: 93] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Revised: 10/20/2017] [Indexed: 05/08/2023]
Abstract
The last decade has seen dramatic progress in the principle, design, and fabrication of photonic nanomaterials with various optical properties and functionalities. Light-emitting and light-responsive nanomaterials, such as semiconductor quantum dots, plasmonic metal nanoparticles, organic carbon, and polymeric nanomaterials, offer promising approaches to low-cost and effective diagnostic, therapeutic, and theranostic applications. Reasonable endeavors have begun to translate some of the promising photonic nanomaterials to the clinic. Here, current research on the state-of-the-art and emerging photonic nanomaterials for diverse biomedical applications is reviewed, and the remaining challenges and future perspectives are discussed.
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Affiliation(s)
- Hyemin Kim
- PHI BIOMED Co., #613, 12 Gangnam-daero 65-gil, Seocho-gu, Seoul, 06612, South Korea
| | - Songeun Beack
- Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk, 37673, South Korea
| | - Seulgi Han
- Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk, 37673, South Korea
| | - Myeonghwan Shin
- Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk, 37673, South Korea
| | - Taehyung Lee
- Department of Chemical Engineering, POSTECH, 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk, 37673, South Korea
| | - Yoonsang Park
- Department of Chemical Engineering, POSTECH, 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk, 37673, South Korea
| | - Ki Su Kim
- Wellman Center for Photomedicine, Massachusetts General Hospital, 65 Landsdowne St., UP-5, Cambridge, MA, 02139, USA
| | - Ali K Yetisen
- Wellman Center for Photomedicine, Massachusetts General Hospital, 65 Landsdowne St., UP-5, Cambridge, MA, 02139, USA
| | - Seok Hyun Yun
- Wellman Center for Photomedicine, Massachusetts General Hospital, 65 Landsdowne St., UP-5, Cambridge, MA, 02139, USA
| | - Woosung Kwon
- Department of Chemical and Biological Engineering, Sookmyung Women's University, 100 Cheongpa-ro 47-gil, Seoul, 04310, South Korea
| | - Sei Kwang Hahn
- Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk, 37673, South Korea
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38
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Sun J, Zhou Q, Yang S. Label-free photoacoustic imaging guided sclerotherapy for vascular malformations: a feasibility study. OPTICS EXPRESS 2018; 26:4967-4978. [PMID: 29475340 DOI: 10.1364/oe.26.004967] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 02/12/2018] [Indexed: 06/08/2023]
Abstract
We used high-resolution photoacoustic imaging (PAI) to guide sclerotherapy of vascular malformations in an in vivo animal model. A focus-adjustable PAI system was developed. It can adapt to the imaging needs of different depths by adjusting the focus. Blood samples drawn before and after sclerosis were examined with PAI, which could distinguish whether or not the blood had been exposed to a sclerosing agent. Superficial and deep vessels in the animal model were examined in vivo to prove the feasibility of guiding sclerotherapy. We found that PAI can distinguish sclerotic vessels from normal vessels within a certain depth range. Our findings suggest the potential of PAI to find accurate injection points and to localize thrombi, making it possible to reduce the dosage of sclerosing agents.
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Bagheri S, Yasemi M, Safaie-Qamsari E, Rashidiani J, Abkar M, Hassani M, Mirhosseini SA, Kooshki H. Using gold nanoparticles in diagnosis and treatment of melanoma cancer. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2018; 46:462-471. [DOI: 10.1080/21691401.2018.1430585] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Salman Bagheri
- Nano Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Yasemi
- Department of Cell and Molecular Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Elmira Safaie-Qamsari
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Jamal Rashidiani
- Nano Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Morteza Abkar
- Nanomedicine and Nanobiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahmoud Hassani
- Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Ali Mirhosseini
- Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Hamid Kooshki
- Nano Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
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40
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McLaughlan JR, Cowell DMJ, Freear S. Gold nanoparticle nucleated cavitation for enhanced high intensity focused ultrasound therapy. Phys Med Biol 2017; 63:015004. [PMID: 29098986 DOI: 10.1088/1361-6560/aa97e9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
High intensity focused ultrasound (HIFU) or focused ultrasound surgery is a non-invasive technique for the treatment of cancerous tissue, which is limited by difficulties in getting real-time feedback on treatment progress and long treatment durations. The formation and activity of acoustic cavitation, specifically inertial cavitation, during HIFU exposures has been demonstrated to enhance heating rates. However, without the introduction of external nuclei its formation an activity can be unpredictable, and potentially counter-productive. In this study, a combination of pulse laser illumination (839 nm), HIFU exposures (3.3 MHz) and plasmonic gold nanorods (AuNR) was demonstrated as a new approach for the guidance and enhancement of HIFU treatments. For imaging, short duration HIFU pulses (10 μs) demonstrated broadband acoustic emissions from AuNR nucleated cavitation with a signal-to-noise ranging from 5-35 dB for peak negative pressures between 1.19-3.19 ± 0.01 MPa. In the absence of either AuNR or laser illumination these emissions were either not present or lower in magnitude (e.g. 5 dB for 3.19 MPa). Continuous wave (CW) HIFU exposures for 15 s, were then used to generate thermal lesions for peak negative pressures from 0.2-2.71 ± 0.01 MPa at a fluence of 3.4 mJ [Formula: see text]. Inertial cavitation dose (ICD) was monitored during all CW exposures, where exposures combined with both laser illumination and AuNRs resulted in the highest level of detectable emissions. This parameter was integrated over the entire exposure to give a metric to compare with measured thermal lesion area, where it was found that a minimum total ICD of [Formula: see text] a.u. was correlated with the formation of thermal lesions in gel phantoms. Furthermore, lesion area (mm2) was increased for equivalent exposures without either AuNRs or laser illumination. Once combined with cancer targeting AuNRs this approach could allow for the future theranostic use of HIFU, such as providing the ability to identify and treat small multi-focal cancerous regions with minimal damage to surrounding healthy tissue.
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Affiliation(s)
- J R McLaughlan
- School of Electronic and Electrical Engineering, University of Leeds, Leeds, LS2 9JT, United Kingdom. Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, LS9 7TF, United Kingdom
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Harris-Birtill D, Singh M, Zhou Y, Shah A, Ruenraroengsak P, Gallina ME, Hanna GB, Cass AEG, Porter AE, Bamber J, Elson DS. Gold nanorod reshaping in vitro and in vivo using a continuous wave laser. PLoS One 2017; 12:e0185990. [PMID: 29045438 PMCID: PMC5646757 DOI: 10.1371/journal.pone.0185990] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 09/23/2017] [Indexed: 11/19/2022] Open
Abstract
Gold nanorods (GNRs) are increasingly being investigated for cancer theranostics as they possess features which lend themselves in equal measures as contrast agents and catalysts for photothermal therapy. Their optical absorption spectral peak wavelength is determined by their size and shape. Photothermal therapy using GNRs is typically established using near infrared light as this allows sufficient penetration into the tumour matrix. Continuous wave (CW) lasers are the most commonly applied source of near infrared irradiation on GNRs for tumour photothermal therapy. It is perceived that large tumours may require fractionated or prolonged irradiation. However the true efficacy of repeated or protracted CW irradiation on tumour sites using the original sample of GNRs remains unclear. In this study spectroscopy and transmission electron microscopy are used to demonstrate that GNRs reshape both in vitro and in vivo after CW irradiation, which reduces their absorption efficiency. These changes were sustained throughout and beyond the initial period of irradiation, resulting from a spectral blue-shift and a considerable diminution in the absorption peak of GNRs. Solid subcutaneous tumours in immunodeficient BALB/c mice were subjected to GNRs and analysed with electron microscopy pre- and post-CW laser irradiation. This phenomenon of thermally induced GNR reshaping can occur at relatively low bulk temperatures, well below the bulk melting point of gold. Photoacoustic monitoring of GNR reshaping is also evaluated as a potential clinical aid to determine GNR absorption and reshaping during photothermal therapy. Aggregation of particles was coincidentally observed following CW irradiation, which would further diminish the subsequent optical absorption capacity of irradiated GNRs. It is thus established that sequential or prolonged applications of CW laser will not confer any additional photothermal effect on tumours due to significant attenuations in the peak optical absorption properties of GNRs following primary laser irradiation.
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Affiliation(s)
- David Harris-Birtill
- Hamlyn Centre for Robotic Surgery, Imperial College London, London, United Kingdom
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Mohan Singh
- Hamlyn Centre for Robotic Surgery, Imperial College London, London, United Kingdom
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Yu Zhou
- Department of Chemistry, Imperial College London, London, United Kingdom
| | - Anant Shah
- Joint Department of Physics and CRUK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, London, United Kingdom
| | - Pakatip Ruenraroengsak
- Hamlyn Centre for Robotic Surgery, Imperial College London, London, United Kingdom
- Department of Materials and London Centre for Nanotechnology, Imperial College London, London, United Kingdom
| | - Maria Elena Gallina
- Hamlyn Centre for Robotic Surgery, Imperial College London, London, United Kingdom
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - George B. Hanna
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Anthony E. G. Cass
- Department of Chemistry, Imperial College London, London, United Kingdom
| | - Alexandra E. Porter
- Department of Materials and London Centre for Nanotechnology, Imperial College London, London, United Kingdom
| | - Jeffrey Bamber
- Joint Department of Physics and CRUK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, London, United Kingdom
| | - Daniel S. Elson
- Hamlyn Centre for Robotic Surgery, Imperial College London, London, United Kingdom
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
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Dynamic contrast-enhanced photoacoustic imaging using photothermal stimuli-responsive composite nanomodulators. Nat Commun 2017; 8:15782. [PMID: 28593942 PMCID: PMC5472754 DOI: 10.1038/ncomms15782] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Accepted: 04/27/2017] [Indexed: 11/26/2022] Open
Abstract
Molecular photoacoustic imaging has shown great potential in medical applications; its sensitivity is normally in pico-to-micro-molar range, dependent on exogenous imaging agents. However, tissue can produce strong background signals, which mask the signals from the imaging agents, resulting in orders of magnitude sensitivity reduction. As such, an elaborate spectral scan is often required to spectrally un-mix the unwanted background signals. Here we show a new single-wavelength photoacoustic dynamic contrast-enhanced imaging technique by employing a stimuli-responsive contrast agent. Our technique can eliminate intrinsic background noises without significant hardware or computational resources. We show that this new contrast agent can generate up to 30 times stronger photoacoustic signals than the concentration-matched inorganic nanoparticle counterparts. By dynamically modulating signals from the contrast agents with an external near-infrared optical stimulus, we can further suppress the background signals leading to an additional increase of more than five-fold in imaging contrast in vivo. Photoacoustic imaging becomes an enabling technology that is designed for clinic diagnosis of disease. Here, Chen et al. report an imaging contrast agent—plasmonic nanoparticles caged in hydrogel subject to reversible volume change depending on temperature, which exhibits tunable photoacoustic signal.
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Varna M, Xuan HV, Fort E. Gold nanoparticles in cardiovascular imaging. WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY 2017; 10. [DOI: 10.1002/wnan.1470] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Revised: 02/01/2017] [Accepted: 02/25/2017] [Indexed: 01/12/2023]
Affiliation(s)
- Mariana Varna
- Institut LangevinESPCI Paris, CNRS, PSL Research UniversityParisFrance
- Institut Galien Paris‐Sud UMR 8612, CNRSUniversité Paris‐Sud/Paris‐Saclay Faculté de PharmacieChâtenay‐MalabryFrance
| | - Hoa V. Xuan
- Institut LangevinESPCI Paris, CNRS, PSL Research UniversityParisFrance
- Faculty of Physics and TechnologyThai Nguyen University of Science (TNUS)Thai NguyenVietnam
| | - Emmanuel Fort
- Institut LangevinESPCI Paris, CNRS, PSL Research UniversityParisFrance
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Sun Q, You Q, Pang X, Tan X, Wang J, Liu L, Guo F, Tan F, Li N. A photoresponsive and rod-shape nanocarrier: Single wavelength of light triggered photothermal and photodynamic therapy based on AuNRs-capped & Ce6-doped mesoporous silica nanorods. Biomaterials 2017; 122:188-200. [DOI: 10.1016/j.biomaterials.2017.01.021] [Citation(s) in RCA: 112] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Revised: 01/05/2017] [Accepted: 01/16/2017] [Indexed: 01/21/2023]
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Manivasagan P, Quang Bui N, Bharathiraja S, Santha Moorthy M, Oh YO, Song K, Seo H, Yoon M, Oh J. Multifunctional biocompatible chitosan-polypyrrole nanocomposites as novel agents for photoacoustic imaging-guided photothermal ablation of cancer. Sci Rep 2017; 7:43593. [PMID: 28252638 PMCID: PMC5333628 DOI: 10.1038/srep43593] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 01/25/2017] [Indexed: 12/15/2022] Open
Abstract
Cancer nanotechnology is emerging as one of the promising strategies combining photothermal therapy (PTT) and photoacoustic imaging (PAI) for the treatment of breast cancer and it has received considerable attention in the recent years because it is minimally invasive, prevents damage to non-targeted regions, permits fast recovery, and involves breast cancer imaging. The present study demonstrates multifunctional biocompatible chitosan-polypyrrole nanocomposites (CS-PPy NCs) as novel agents for photoacoustic imaging-guided photothermal ablation of cancer because of their biocompatibility, conductivity, stability, and strong near-infrared (NIR) absorbance. The CS-PPy NCs are spherical in shape and range 26–94 nm in size with a mean value of 50.54 ± 2.56 nm. The in vitro results demonstrated good biocompatibility of CS-PPy NCs, which can be used in PTT for cancer cells under 808-nm NIR laser irradiation. Tumor-bearing mice fully recovered after treatment with CS-PPy NCs and NIR 808-nm laser irradiation compared to the corresponding control groups. Our research highlights the promising potential of using CS-PPy NCs for photoacoustic imaging-guided photothermal ablation of cancer in preclinical animals, which should be verified in future clinical trials.
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Affiliation(s)
- Panchanathan Manivasagan
- Marine-Integrated Bionics Research Center, Pukyong National University, Busan 48513, Republic of Korea
| | - Nhat Quang Bui
- Department of Biomedical Engineering and Center for Marine-Integrated Biotechnology (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea
| | - Subramaniyan Bharathiraja
- Marine-Integrated Bionics Research Center, Pukyong National University, Busan 48513, Republic of Korea
| | - Madhappan Santha Moorthy
- Marine-Integrated Bionics Research Center, Pukyong National University, Busan 48513, Republic of Korea
| | - Yun-Ok Oh
- Marine-Integrated Bionics Research Center, Pukyong National University, Busan 48513, Republic of Korea
| | - Kyeongeun Song
- Department of Biomedical Engineering and Center for Marine-Integrated Biotechnology (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea
| | - Hansu Seo
- Department of Biomedical Engineering and Center for Marine-Integrated Biotechnology (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea
| | - Min Yoon
- Department of statistics, College of Natural of Sciences, Pukyong National University, Busan, 48513, Republic of Korea
| | - Junghwan Oh
- Marine-Integrated Bionics Research Center, Pukyong National University, Busan 48513, Republic of Korea.,Department of Biomedical Engineering and Center for Marine-Integrated Biotechnology (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea
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Tian C, Qian W, Shao X, Xie Z, Cheng X, Liu S, Cheng Q, Liu B, Wang X. Plasmonic Nanoparticles with Quantitatively Controlled Bioconjugation for Photoacoustic Imaging of Live Cancer Cells. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2016; 3:1600237. [PMID: 27981012 PMCID: PMC5157183 DOI: 10.1002/advs.201600237] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Revised: 07/04/2016] [Indexed: 05/18/2023]
Abstract
Detection and imaging of single cancer cells is critical for cancer diagnosis and understanding of cellular dynamics. Photoacoustic imaging (PAI) provides a potential tool for the study of cancer cell dynamics, but faces the challenge that most cancer cells lack sufficient endogenous contrast. Here, a type of colloidal gold nanoparticles (AuNPs) are physically fabricated and are precisely functionalized with quantitative amounts of functional ligands (i.e., polyethyleneglycol (PEG) and (Arginine(R)-Glycine(G)-Aspartic(D))4 (RGD) peptides) to serve as an exogenous contrast agent for PAI of single cells. The functionalized AuNPs, with a fixed number of PEG but different RGD densities, are delivered into human prostate cancer cells. Radioactivity and photoacoustic analyses show that, although cellular uptake efficiency of the AuNPs linearly increases along with RGD density, photoacoustic signal generation efficiency does not and only maximize at a moderate RGD density. The functionalization of the AuNPs is in turn optimized based on the experimental finding, and single cancer cells are imaged using a custom photoacoustic microscopy with high-resolution. The quantitatively functionalized AuNPs together with the high-resolution PAI system provide a unique platform for the detection and imaging of single cancer cells, and may impact not only basic science but also clinical diagnostics on a range of cancers.
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Affiliation(s)
- Chao Tian
- Department of Biomedical EngineeringUniversity of MichiganAnn ArborMI48109USA
| | - Wei Qian
- IMRA America, IncAnn ArborMI48105USA
| | - Xia Shao
- Department of RadiologyUniversity of MichiganAnn ArborMI48109USA
| | - Zhixing Xie
- Department of RadiologyUniversity of MichiganAnn ArborMI48109USA
| | - Xu Cheng
- Department of UrologyUniversity of MichiganAnn ArborMI48109USA
| | - Shengchun Liu
- College of Physical Science and TechnologyHeilongjiang UniversityHarbin150080China
| | - Qian Cheng
- Institute of AcousticsTongji UniversityShanghai200092China
| | - Bing Liu
- IMRA America, IncAnn ArborMI48105USA
| | - Xueding Wang
- Department of Biomedical EngineeringUniversity of MichiganAnn ArborMI48109USA
- Department of RadiologyUniversity of MichiganAnn ArborMI48109USA
- Institute of AcousticsTongji UniversityShanghai200092China
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Chen Q, Liu Z. Albumin Carriers for Cancer Theranostics: A Conventional Platform with New Promise. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2016; 28:10557-10566. [PMID: 27111654 DOI: 10.1002/adma.201600038] [Citation(s) in RCA: 209] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 02/05/2016] [Indexed: 05/21/2023]
Abstract
Theranostic nanoplatforms with integrated diagnostic and therapeutic functions, aiming at imaging-guided therapy to improve treatment planning, as well as combination therapy to enhance treatment efficacy, have received tremendous attention in recent years. Among numerous types of functional nanomaterials explored in this field, protein-based nanocarriers with inherent biocompatibility have also been selected as building blocks to construct multifunctional theranostic platforms. In particular, albumin, which has been extensively used as drug-delivery carriers for decades, has shown great new promise in the construction of novel imaging and therapeutic nanoagents, as demonstrated by a number of recent studies. IHere, the motivations of using albumins to build up nanoscale theranostics are discussed, and the latest progress/future perspectives in this direction are summarized.
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Affiliation(s)
- Qian Chen
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University Suzhou, Jiangsu, 215123, China
| | - Zhuang Liu
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University Suzhou, Jiangsu, 215123, China
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Manivasagan P, Bharathiraja S, Bui NQ, Jang B, Oh YO, Lim IG, Oh J. Doxorubicin-loaded fucoidan capped gold nanoparticles for drug delivery and photoacoustic imaging. Int J Biol Macromol 2016; 91:578-88. [DOI: 10.1016/j.ijbiomac.2016.06.007] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Revised: 05/11/2016] [Accepted: 06/02/2016] [Indexed: 12/22/2022]
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49
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Chen W, Zhang S, Yu Y, Zhang H, He Q. Structural-Engineering Rationales of Gold Nanoparticles for Cancer Theranostics. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2016; 28:8567-8585. [PMID: 27461909 DOI: 10.1002/adma.201602080] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Revised: 06/02/2016] [Indexed: 05/20/2023]
Abstract
Personalized theranostics of cancer is increasingly desired, and can be realized by virtue of multifunctional nanomaterials with possible high performances. Gold nanoparticles (GNPs) are a type of especially promising candidate for cancer theranostics, because their synthesis and modification are facile, their structures and physicochemical properties are flexibly controlled, and they are also biocompatible. Especially, the localized surface plasmon resonance and multivalent coordination effects on the surface endow them with NIR light-triggered photothermal imaging and therapy, controlled drug release, and targeted drug delivery. Although the structure, properties, and theranostic application of GNPs are considerably plentiful, no expert review systematically explains the relationships among their structure, property. and application and induces the engineering rationales of GNPs for cancer theranostics. Hence, there are no clear rules to guide the facile construction of optimal GNP structures aiming at a specific theranostic application. A series of structural-engineering rationales of GNPs for cancer theranostics is proposed through digging out the deep relationships between the structure and properties of GNPs. These rationales will be inspiring for guiding the engineering of specific and advanced GNPs for personalized cancer theranostics.
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Affiliation(s)
- Wenwen Chen
- National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, No. 3688 Nanhai Road, Nanshan District, Shenzhen, 518060, Guangdong, P. R. China
| | - Shaohua Zhang
- Department of Breast Cancer, Affiliated Hospital of Academy of Military Medical Sciences, No. 8 Dongdajie, Beijing, 100071, P. R. China
| | - Yangyang Yu
- National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, No. 3688 Nanhai Road, Nanshan District, Shenzhen, 518060, Guangdong, P. R. China
| | - Huisheng Zhang
- National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, No. 3688 Nanhai Road, Nanshan District, Shenzhen, 518060, Guangdong, P. R. China
| | - Qianjun He
- National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, No. 3688 Nanhai Road, Nanshan District, Shenzhen, 518060, Guangdong, P. R. China.
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Abstract
CLINICAL/METHODICAL ISSUE Imaging modalities play an increasing role in today's medical diagnostics. Among them, ultrasound (US) is one the most widespread techniques although it has relatively poor soft tissue contrast. Furthermore, US is poorly suited as a modality for molecular imaging (MI). STANDARD RADIOLOGICAL METHODS Methods such as Doppler and contrast-enhanced US (CEUS) allow functional imaging of the vasculature; however, ultrasound-based MI remains limited to the vascular network due to the size of available contrast agents. METHODICAL INNOVATIONS Optoacoustic imaging combines the benefits of optics (high contrast) with those of acoustics (low scattering and high resolution). In this technique, signals are generated in tissue with high contrast depending on the local optical absorption coefficient and detected with an acoustic procedure. PERFORMANCE Optoacoustic imaging can intrinsically be scaled in terms of resolution and is therefore usable in various applications from in vitro microscopy, to preclinical small animal imaging up to clinical imaging. With a resolution in the range of clinical ultrasound systems (100-400 µm), highly scattering tissue can be imaged up to several centimeters in depth. ACHIEVEMENTS In contrast to conventional ultrasound imaging, optoacoustic techniques are highly suitable for MI. Various contrast agents as well as different technical implementations of the approach have already been preclinically evaluated. The technique is currently close to being transferred to clinical implementation and the first studies have already been started. PRACTICAL RECOMMENDATIONS Clinical studies are ongoing with respect to early diagnosis of breast cancer and arthritis. Furthermore, the suitability of the technique for skin imaging is currently being investigated.
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Affiliation(s)
- M Fournelle
- Fraunhofer Institut für Biomedizinische Technik IBMT, Ensheimer Str. 48, 66386, St. Ingbert, Deutschland.
| | - S Tretbar
- Fraunhofer Institut für Biomedizinische Technik IBMT, Ensheimer Str. 48, 66386, St. Ingbert, Deutschland
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