Cervical cancer is an aggressive type of cancer affecting women worldwide. Many affected individuals rely on smear tests for the diagnosis, surgery, chemotherapy, or radiation for their treatment. However, due to a broad set of undesired results and side-effects associated with the existing protocols, the search for better diagnostic and therapeutic interventions is a never-ending pursuit. In the purview, the bio-concentration of trace elements (copper, selenium, zinc, iron, arsenic, manganese, and cadmium) is seen to fluctuate during the occurrence of cervical cancer and its progression from pre-cancerous to metastatic nature. Thus, during the occurrence of cervical cancer, the detection of trace elements and their supplementation will prove to be highly advantageous in developing diagnostic tools and therapeutics, respectively. This review provides a detailed overview of cervical cancer, its encouragement by human papillomavirus infections, the mechanism of pathology, and resistance. Majorly, the review emphasizes the less explored role of trace elements, their contribution to the growth and inhibition of cervical cancer. Numerous clinical trials have been listed, thereby providing a comprehensive reference to the exploration of trace elements in the management of cervical cancer.

Magnetic resonance imaging (MRI) is a clinical imaging modality that provides high-resolution images of soft tissues, including cancerous lesions. Stable gadolinium(III) chelates have been used as contrast agents (CA) in MRI to enhance the contrast between the tissues of interest and surrounding tissues for accurate diagnostic imaging. Magnetic resonance molecular imaging (MRMI) of cancer requires targeted CA to specifically elucidate cancer-associated molecular processes and can provide high-resolution delineation and characterization of cancer for precision medicine. The main challenge for MRMI is the lack of sufficient sensitivity to detect the low concentration of the cellular oncogenic markers. In addition, targeted CA must satisfy regulatory safety requirements prior to clinical development. Up to now, there is no FDA-approved targeted CA for MRMI of cancer.In this Account, we discuss the latest developments in the design and development of clinically translatable targeted CA for MRMI of cancer, with an emphasis on our own research. The primary limitation of MRMI can be overcome by designing small molecular targeted CA to target abundant cancer-specific targets found in the tumor microenvironment (TME). For example, aggressive tumors have a unique extracellular matrix (ECM) composed of oncoproteins, which can be used as targetable markers for MRMI. We have designed and prepared small peptide conjugates of clinical contrast agents, including Gd-DTPA and Gd-DOTA, to target fibrin-fibronectin clots in tumors. These small molecular CA have been effective in enhancing MRMI detection of solid tumors and have demonstrated the ability to detect submillimeter cancer micrometastases in mouse tumor models, exceeding the detection limit of current clinical imaging modalities. We have also identified extradomain B fibronectin (EDB-FN), an oncofetal subtype of fibronectin, as a promising TME target to leverage in the design and development of small peptide targeted CA for clinical translation. The expression level of EDB-FN is correlated with invasiveness of cancer cells and poor patient survival of multiple cancer types. ZD2 peptide with a sequence of seven amino acids (TVRTSAD) was identified to specifically bind to the EDB protein fragment. Several ZD2 conjugates of macrocyclic GBCA, including Gd-DOTA and Gd(HP-DO3A), have been synthesized and tested in mouse tumor models. ZD2-N3-Gd(HP-DO3A) (MT218) with a high r₁ relaxivity was selected as the lead agent for clinical translation. The physicochemical properties and preclinical assessments of MT218 are summarized in this Account. MRMI of EDB-FN with MT218 can effectively detect invasive tumors of multiple cancers with risk-stratification and monitor tumor response to anticancer therapies in mouse models. Currently, MT218 is in clinical trials for precision cancer MRMI. Herein, we will show that using targeted MRI contrast agents specific to abundant TME biomarkers is a pragmatic solution for effective precision cancer imaging in high spatial resolution. And thus, we illustrate a replicable approach for CA development that is vital for cancer MRMI.

Considerable breakthroughs in the treatment of malignant tumors using antibody drugs, especially immunomodulating monoclonal antibodies (mAbs), have been made in the past decade. Despite technological advancements in antibody design and manufacture, multiple challenges face antibody-mediated cancer therapy, such as instability in vivo, poor tumor penetration, limited response rate, and undesirable off-target cytotoxicity. In recent years, an increasing number of biomaterials-based delivery systems have been reported to enhance the antitumor efficacy of antibody drugs. This review summarizes the advances and breakthroughs in integrating biomaterials with therapeutic antibodies for enhanced cancer therapy. A brief introduction to the principal mechanism of antibody-based cancer therapy is first established, and then various antibody immobilization strategies are provided. Finally, the current state-of-the-art in biomaterials-based antibody delivery systems and their applications in cancer treatment are summarized, highlighting how the delivery systems augment the therapeutic efficacy of antibody drugs. The outlook and perspective on biomaterials-based delivery of antitumor antibodies are also discussed.

The targeted delivery of anticancer agents to tumor is a major challenge because most of the drugs show off-target effect resulting in nonspecific cell death. Multifunctionalized metallic nanoparticles (NPs) are explored as new carrier system in the era of cancer therapeutics. Researchers investigated the potential of metallic NPs to target tumor cells by active and passive mechanisms, thereby reducing off-target effects of anticancer agents. Moreover, photocatalytic activity of upconversion nanoparticles (UCNPs) and the enhanced permeation and retention (EPR) effect have also gained wide potential in cancer treatment. Recent advancement in the field of nanotechnology highlights their potency for cancer therapy.

This review summarizes the types of gold and silver metallic NPs with targeting mechanisms and their potentiality in cancer therapy.

Recent advances in the field of nanotechnology for cancer therapy offer high specificity and targeting efficiency. Targeting tumor cells through mechanistic pathways using metallic NPs for the disruption/alteration of molecular profile and survival rate of the tumor cells has led to an effective approach for cancer therapeutics. This alteration in the survival rate of the tumor cells might decrease the proliferation thereby resulting in more efficient management in the treatment of cancer.

Recently, exosomes have gained attention as an effective tool for early cancer detection. Almost all types of cells release exosomes, making them substantially important for disease diagnosis. In this study, we have utilized HepG2 cancer cells for the in situ biosynthesis of silver and iron oxide nanoclusters (NCs) from their respective salts (i.e., AgNO3 and FeCl2, respectively) in the presence of glutathione (GSH). The self-assembled biosynthesized silver and iron NCs were readily loaded on exosomes as payloads and secreted into the cell culture medium. The cargo loaded exosomes were then isolated and characterized by electron microscopy for nano-silver and iron oxide NC confirmation. Ag NCs have potential as a fluorescent probe and Fe3O4 NCs as a contrast agent for CT and MRI. Furthermore, these isolated exosomes from HepG2 cancer cells have a significant influence on cellular uptake and cell viability when exposed to both HepG2 and U87 cancer cells. These findings demonstrate that the biocompatible nature of these self-assembled NCs loaded on exosomes could be utilized to bioimage cancer in the initial stages through fluorescence imaging.

This paper reviews recent developments in the preparation, surface functionalization, and applications of Fe₃O₄ magnetic nanoparticles. Especially, it includes preparation methods (such as electrodeposition, polyol methods, etc.), organic materials (such as polymers, small molecules, surfactants, biomolecules, etc.) or inorganic materials (such as silica, metals, and metal oxidation/sulfide, functionalized coating of carbon surface, graphene, etc.) and its applications (such as magnetic separation, protein fixation, magnetic catalyst, environmental treatment, medical research, etc.). In the end, some existing challenges and possible future trends in the field were discussed.

A "smart" core@shell composite nanoparticle (NP) having dual-response mechanisms (i.e., temperature and light) was synthesized, and its efficacy in the loading and release of small molecules was explored. These core@shell NPs are composed of an optically active gold nanoshell (GNS) core and a mesoporous (m-) silica layer (m-SiO2). The GNS@m-SiO2 nanoparticles are further encapsulated within a thermo-responsive poly(N-isopropylacrylamide-co-acrylic acid) hydrogel (PNIPAM-co-AA). The multi-responsive composite NPs were designed to create thermally and optically modulated drug-delivery vehicles with a m-SiO2 layer providing additional non-collapsible space for drug storage. The influence of the m-SiO2 layer on the efficacy of loading and release of methylene blue, which serves as a model for a small-molecule therapeutic drug, was evaluated. The "smart" core@shell composite NPs having a m-SiO2 layer demonstrated an improved capacity to load and release small molecules compared to the corresponding NPs with no m-SiO2 shell. Additionally, an efficient response by the composite NPs was successfully induced by the thermal energy generated from the gold nanoshell core upon exposure to near infrared (NIR) stimulation.

In order to translate nanotechnology into medical practice, magnetic nanoparticles (MNPs) have been presented as a class of non-invasive nanomaterials for numerous biomedical applications. In particular, MNPs have opened a door for simultaneous diagnosis and brisk treatment of diseases in the form of theranostic agents. This review highlights the recent advances in preparation and utilization of MNPs from the synthesis and functionalization steps to the final design consideration in evading the body immune system for therapeutic and diagnostic applications with addressing the most recent examples of the literature in each section. This study provides a conceptual framework of a wide range of synthetic routes classified mainly as wet chemistry, state-of-the-art microfluidic reactors, and biogenic routes, along with the most popular coating materials to stabilize resultant MNPs. Additionally, key aspects of prolonging the half-life of MNPs via overcoming the sequential biological barriers are covered through unraveling the biophysical interactions at the bio-nano interface and giving a set of criteria to efficiently modulate MNPs' physicochemical properties. Furthermore, concepts of passive and active targeting for successful cell internalization, by respectively exploiting the unique properties of cancers and novel targeting ligands are described in detail. Finally, this study extensively covers the recent developments in magnetic drug targeting and hyperthermia as therapeutic applications of MNPs. In addition, multi-modal imaging via fusion of magnetic resonance imaging, and also innovative magnetic particle imaging with other imaging techniques for early diagnosis of diseases are extensively provided.

Nowadays, magnetic nanoparticles (MNPs) have received much attention because of their enormous potentials in many fields such as magnetic fluid hyperthermia (MFH). The goal of hyperthermia is to increase the temperature of malignant cells to destroy them without any lethal effect on normal tissues. To investigate the effectiveness of cancer therapy by magnetic fluid hyperthermia, Fe0.5Zn0.5Fe2O4 nanoparticles (FNPs) were used to undergo external magnetic field (f=515 kHz, H=100 G) in mice bearing implanted tumor.

FNPs were synthesized via precipitation and characterized using transmission electron microscopy (TEM), vibrating sample magnetometer, and Fourier transform infrared. For in vivo study, the mice bearing implanted tumor were divided into four groups (two mice per group), namely, control group, AMF group, MNPs group, and MNPs&AMF group. After 24 hours, the mice were sacrificed and each tumor specimen was prepared for histological analyses. The necrotic surface area was estimated by using graticule (Olympus, Japan) on tumor slides.

The mean diameter of FNPs was estimated around 9 nm by TEM image and M versus H curve indicates that this particle is among superparamagnetic materials. According to histological analyses, no significant difference in necrosis extent was observed among the four groups.

FNPs are biocompatible and have a good size for biomedical applications. However, for MFH approach, larger diameters especially in the range of ferromagnetic particles due to hysteresis loss can induce efficient heat in the target region.

Nanoparticles decorated with biocompatible coatings have received considerable attention in recent years for their potential biomedical applications. However, the desirable properties of nanoparticles for in vivo uses, such as colloidal stability, biodistribution, and pharmacokinetics, require further research. In this work, we report a bio-derived zwitterionic surface ligand, cysteine betaine (Cys-b) for the modification of hollow gold-silver nanoshells, giving rise to hyperthermia applications. Cys-b coatings on planar substrates and nanoshells were compared to conventional (11-mercaptoundecyl)tri(ethylene glycol) (OEG-thiol) to investigate their effects on the fouling resistance, colloidal stability, environmental tolerance, and photothermal properties. The results found that Cys-b and OEG-thiol coatings exhibited comparable antifouling properties against bacteria of gram-negative Pseudomonas aeruginosa (P. aeruginosa) and gram-positive Staphylococcus epidermidis (S. epidermidis), NIH-3T3 fibroblasts, and bovine serum albumin. However, when the modified nanoshells were suspended at a temperature of 50°C in aqueous 3M NaCl solutions, shifts in the extinction maximum of the OEG-capped nanoshells with time were observed, while the corresponding spectra of nanoshells capped with Cys-b generally remained unchanged. In addition, when the nanoshells were continuously exposed to NIR irradiation, the temperature of the solution containing nanoshells capped with Cys-b increased to a plateau of 54°C, while that of the OEG-capped nanoshells gradually decreased after reaching a peak temperature. Accordingly, the Cys-b nanoshells were conjugated with anti-HER2 antibodies for targeted delivery to HER2-positive MDA-MB-453 breast cancer cells for hyperthermia treatment. The results showed the selective delivery and effective photothermal cell ablation with the antibody-conjugated Cys-b nanoshells. Therefore, this work demonstrated the promise of bio-derived zwitterionic Cys-b as a stable and biocompatible surface coating for materials in nanomedicine.

Research and treatment in the nervous system is challenged by many physiological barriers posing a major hurdle for neurologists. The CNS is protected by a formidable blood brain barrier (BBB) which limits surgical, therapeutic and diagnostic interventions. The hostile environment created by reactive astrocytes in the CNS along with the limited regeneration capacity of the PNS makes functional recovery after tissue damage difficult and inefficient. Nanomaterials have the unique ability to interface with neural tissue in the nano-scale and are capable of influencing the function of a single neuron. The ability of nanoparticles to transcend the BBB through surface modifications has been exploited in various neuro-imaging techniques and for targeted drug delivery. The tunable topography of nanofibers provides accurate spatio-temporal guidance to regenerating axons. This review is an attempt to comprehend the progress in understanding the obstacles posed by the complex physiology of the nervous system and the innovations in design and fabrication of advanced nanomaterials drawing inspiration from natural phenomenon. We also discuss the development of nanomaterials for use in Neuro-diagnostics, Neuro-therapy and the fabrication of advanced nano-devices for use in opto-electronic and ultrasensitive electrophysiological applications. The energy efficient and parallel computing ability of the human brain has inspired the design of advanced nanotechnology based computational systems. However, extensive use of nanomaterials in neuroscience also raises serious toxicity issues as well as ethical concerns regarding nano implants in the brain. In conclusion we summarize these challenges and provide an insight into the huge potential of nanotechnology platforms in neuroscience.

The selective action of drugs in tumor cells is a major problem in cancer therapy. Most chemotherapy drugs act nonspecifically and damage both cancer and healthy cells causing various side effects. In this study, the preparation of a selective drug delivery system, which is able to act as a carrier for hydrophobic and anticancer drugs is reported. Amino-functionalized silica nanoparticles loaded with curcumin were successfully synthesized via sol-gel approach and duly characterized. Thereafter, the targeting ligand, folate, was covalently attached to amino groups of nanoparticle surface through amide bond formation. The cytotoxic effect of nanoparticles on prostate cancer cells line was evaluated and compared to normal cells line (prostate epithelial cell). Cytotoxicity experiments demonstrated that folate-functionalized nanoparticles were significantly cytotoxic to tumor cells, whereas normal cells were much less affected by the presence of these structures.

Favorable physiochemical properties and the capability to accommodate targeting moieties make superparamegnetic iron oxide nanoparticles (SPIONs) popular theranostic agents. In this study, we engineered SPIONs for magnetic resonance imaging (MRI) and photothermal therapy of colon cancer cells. SPIONs were synthesized by microemulsion method and were then coated with gold to reduce their cytotoxicity and to confer photothermal capabilities. Subsequently, the NPs were conjugated with thiol modified MUC-1 aptamers. The resulting NPs were spherical, monodisperse and about 19nm in size, as shown by differential light scattering (DLS) and transmission electron microscopy (TEM). UV and X-ray photoelectron spectroscopy (XPS) confirmed the successful gold coating. MTT results showed that Au@SPIONs have insignificant cytotoxicity at the concentration range of 10-100μg/ml (P>0.05) and that NPs covered with protein corona exerted lower cytotoxicity than bare NPs. Furthermore, confocal microscopy confirmed the higher uptake of aptamer-Au@SPIONs in comparison with non-targeted SPIONs. MR imaging revealed that SPIONs produced significant contrast enhancement in vitro and they could be exploited as contrast agents. Finally, cells treated with aptamer-Au@SPIONs exhibited a higher death rate compared to control cells upon exposure to near infrared light (NIR). In conclusion, MUC1-aptamer targeted Au@SPIONs could serve as promising theranostic agents for simultaneous MR imaging and photothermal therapy of cancer cells.

Nanomedicine, the integration of nanotechnological tools in medicine demonstrated promising potential to revolutionize the diagnosis and treatment of various human health conditions. Nanoparticles (NPs) have shown much promise in diagnostics of cancer, especially since they can accommodate targeting molecules on their surface, which search for specific tumor cell receptors upon injection into the blood stream. This concentrates the NPs in the desired tumor location. Furthermore, such receptor-specific targeting may be exploited for detection of potential metastases in an early stage. Some NPs, such as superparamagnetic iron oxide NPs (SPIONs), are also compatible with magnetic resonance imaging (MRI), which makes their clinical translation and application rather easy and accessible for tumor imaging purposes. Furthermore, multifunctional and/or theranostic NPs can be used for simultaneous imaging of cancer and drug delivery. In this review article, we will specifically focus on the application of SPIONs in early detection and imaging of major cancer types.

Super-paramagnetic iron oxide nanoparticles (SPIONs) have been reported by many to be useful as an MRI contrast agent in the detection of tumors. To further enhance the tumor imaging, SPIONs can be coupled with tumor targeting motifs. In this article, the authors performed a comprehensive review on the current status of using targeted SPIONS in tumor detection and also the potential hurdles to overcome.

Magnetic nanoparticles have been widely investigated for their great potential as mediators of heat for localised hyperthermia therapy. Nanocarriers have also attracted increasing attention due to the possibility of delivering drugs at specific locations, therefore limiting systematic effects. The enhancement of the anti-cancer effect of chemotherapy with application of concurrent hyperthermia was noticed more than thirty years ago. However, combining magnetic nanoparticles with molecules of drugs in the same nanoformulation has only recently emerged as a promising tool for the application of hyperthermia with combined chemotherapy in the treatment of cancer. The main feature of this review is to present the recent advances in the development of multifunctional therapeutic nanosystems incorporating both magnetic nanoparticles and drugs, and their superior efficacy in treating cancer compared to either hyperthermia or chemotherapy as standalone therapies. The principle of magnetic fluid hyperthermia is also presented.

The delivery of oligonucleotide antagonists to cytosolic RNA targets such as microRNA represents an avenue for the post-transcriptional control of cellular phenotype. In tumor cells, oncogenic miRNAs, termed oncomirs, are tightly linked to processes that ultimately determine cancer initiation, progression, and response to therapy. Therefore, the capacity to redirect tumor cell fate towards therapeutically beneficial phenotypes holds promise in a future clinical scenario. Previously, we have designed "nanodrugs" for the specific inhibition of oncogenic microRNAs in tumor cells. The basic design of these nanodrugs includes dextran coated iron oxide nanoparticles, conjugated to a tumor-targeting peptide, and a locked nucleic acid (LNA)-modified antisense oligonucleotide that stably binds and inhibits the complementary mature miRNA. Here, we focus on elucidating an optimal nanodrug design for effective miRNA inhibition in tumor cells. Specifically, we investigate the choice of chemical linker for the conjugation of the oligonucleotide to the nanoparticles and evaluate the contribution of tumor-cell targeting to nanodrug uptake and functionality. We find that short labile linkers (SPDP; N-Succinimidyl 3-(2-pyridyldithio)-propionate) are superior to non-labile short linkers (GMBS; N-(gamma-Maleimidobutyryloxy)succinimide ester) or non-labile long linkers (PEG24; Succinimidyl-([N-maleimidopropionamido]-24ethyleneglycol)ester) in terms of their capacity to gain access to the cytosolic cellular compartment and to engage their cognate miRNA. Furthermore, using the nanodrug design that incorporates SPDP as a linker, we establish that the addition of tumor-cell targeting through functionalization of the nanodrug with the alphavbeta3-specific cyclic RGDfK-PEG peptide does not confer an advantage in vitro at long incubation times required for inhibition.

Metalloproteins have long been recognized as key determinants of endogenous contrast in magnetic resonance imaging (MRI) of biological subjects. More recently, both natural and engineered metalloproteins have been harnessed as biotechnological tools to probe gene expression, enzyme activity, and analyte concentrations by MRI. Metalloprotein MRI probes are paramagnetic and function by analogous mechanisms to conventional gadolinium or iron oxide-based MRI contrast agents. Compared with synthetic agents, metalloproteins typically offer worse sensitivity, but the possibilities of using protein engineering and targeted gene expression approaches in conjunction with metalloprotein contrast agents are powerful and sometimes definitive strengths. This review summarizes theoretical and practical aspects of metalloprotein-based contrast agents, and discusses progress in the exploitation of these proteins for molecular imaging applications.

Multiple antibody immobilization methodologies have been developed for several applications including affinity chromatography, immunosensing, and drug delivery. Most of them have been carried out without considering the orientation of the antigen binding site of the antibody, or after the chemical modification of the antibody. An efficient immobilization to improve the biological activity of the antibody is one of the key fundamental issues to pursue. A simple and effective methodology for well-oriented covalently immobilization of antibodies on nanoparticles is reported in this chapter.

Specific bioprobes for single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) have enormous potential for use in cancer imaging in near-future clinical settings. The authors describe the development of dual modality molecular imaging bioprobes, in the form of magnetic nanoparticles (NPs) conjugated to antibodies, for SPECT and MRI of mesothelin-expressing cancers. The bioprobes were developed by conjugating (111)In labeled antimesothelin antibody mAbMB to superparamagnetic iron oxide NPs. Our experimental findings provide evidence that such bioprobes retain their magnetic properties as well as the ability to specifically localize in mesothelin-expressing tumors. It is anticipated that combining SPECT with MR will help obtain both functional and anatomical imaging information with high signal sensitivity and contrast, thereby providing a powerful diagnostic tool for early diagnosis and treatment planning of mesothelin-expressing cancers.

Exercising complementary roles of polymer-coated magnetic nanoparticles for precise drug delivery and image contrast agents has attracted significant attention in biomedical applications. The objective of this study was to prepare and characterize magnetic nanoparticles embedded in polylactide-co-glycolide matrixes (PLGA-MNPs) as a dual drug delivery and imaging system capable of encapsulating both hydrophilic and hydrophobic drugs. PLGA-MNPs were capable of encapsulating both hydrophobic and hydrophilic drugs in a 2:1 ratio. Biocompatibility, cellular uptake, cytotoxicity, membrane potential, and apoptosis were carried out in two different cancer cell lines (MCF-7 and PANC-1). The molecular basis of induction of apoptosis was validated by Western blotting analysis. For targeted delivery of drugs, targeting ligand such as Herceptin was used, and such a conjugated system demonstrated enhanced cellular uptake and an augmented synergistic effect in an in vitro system when compared with native drugs. Magnetic resonance imaging was carried out both in vitro and in vivo to assess the efficacy of PLGA-MNPs as contrast agents. PLGA-MNPs showed a better contrast effect than commercial contrast agents due to higher T(2) relaxivity with a blood circulation half-life ∼ 47 min in the rat model. Thus, our results demonstrated the dual usable purpose of formulated PLGA-MNPs toward either, in therapeutics by delivering different hydrophobic or hydrophilic drugs individually or in combination and imaging for cancer therapeutics in the near future.

We report the fine-tuning of the relaxometry of gamma-Fe2O3@SiO2 core-shell nanoparticles by adjusting the thickness of the coated silica layer. It is clear that the coating thickness of Fe2O3@SiO2 nanoparticles has a significant impact on the r(1) (at low B0 fields), r(2), and r(2)* relaxivities of their aqueous suspensions. These studies clearly indicate that the silica layer is heterogeneous and has regions that are porous to water and others-that are not. It is also shown, that the viability and the mitochondrial dehydrogenase expression of the microglial cells do not appear to be sensitive to the vesicular load with these core-shell nanoparticles. The adequate silica-shell thickness can therefore be tuned to allow for both a sufficiently high response as contrast agent, and-adequate grafting of targeted biomolecules.

Current chemotherapy regimens against pancreatic cancer are met with little success as poor tumor vascularization significantly limits the delivery of oncological drugs. High-dose targeted drug delivery, through which a drug delivery vehicle releases a large payload upon tumor localization, is thus a promising alternative strategy against this lethal disease. Herein, we synthesize anti-carcinoembryonic antigen (CEA) half-antibody conjugated lipid-polymer hybrid nanoparticles and characterize their ligand conjugation yields, physicochemical properties, and targeting ability against pancreatic cancer cells. Under the same drug loading, the half-antibody targeted nanoparticles show enhanced cancer killing effect compared to the corresponding nontargeted nanoparticles.

Dynamic magnetomotion of magnetic nanoparticles (MNPs) detected with magnetomotive optical coherence tomography (MM-OCT) represents a new methodology for contrast enhancement and therapeutic interventions in molecular imaging. In this study, we demonstrate in vivo imaging of dynamic functionalized iron oxide MNPs using MM-OCT in a preclinical mammary tumor model. Using targeted MNPs, in vivo MM-OCT images exhibit strong magnetomotive signals in mammary tumor, and no significant signals were measured from tumors of rats injected with nontargeted MNPs or saline. The results of in vivo MM-OCT are validated by MRI, ex vivo MM-OCT, Prussian blue staining of histological sections, and immunohistochemical analysis of excised tumors and internal organs. The MNPs are antibody functionalized to target the human epidermal growth factor receptor 2 (HER2 neu) protein. Fc-directed conjugation of the antibody to the MNPs aids in reducing uptake by macrophages in the reticulo-endothelial system, thereby increasing the circulation time in the blood. These engineered magnetic nanoprobes have multifunctional capabilities enabling them to be used as dynamic contrast agents in MM-OCT and MRI.

Nanomaterials have widely been used in the field of biological and biomedicine, such as tissue imaging, diagnosis and cancer therapy. In this study, we explored the cytotoxicity and photodynamic effect of different-sized ZnO nanoparticles to target cells. Our observations demonstrated that ZnO nanoparticles exerted dose-dependent and time-dependent cytotoxicity for cancer cells like hepatocellular carcinoma SMMC-7721 cells in vitro. Meanwhile, it was observed that UV irradiation could enhance the suppression ability of ZnO nanoparticles on cancer cells proliferation, and these effects were in the size-dependent manner. Furthermore, when ZnO nanoparticles combined with daunorubicin, the related cytotoxicity of anticancer agents on cancer cells was evidently enhanced, suggesting that ZnO nanoparticles could play an important role in drug delivery. This may offer the possibility of the great potential and promising applications of the ZnO nanoparticles in clinical and biomedical areas like photodynamic cancer therapy and others.

In this study, we report the fabrication of engineered iron oxide magnetic nanoparticles (MNPs) functionalized with anti-human epidermal growth factor receptor type 2 (HER2) antibody to target the tumor antigen HER2. The Fc-directed conjugation of antibodies to the MNPs aids their efficient immunospecific targeting through free Fab portions. The directional specificity of conjugation was verified on a macrophage cell line. Immunofluorescence studies on macrophages treated with functionalized MNPs and free anti-HER2 antibody revealed that the antibody molecules bind to the MNPs predominantly through their Fc portion. Different cell lines with different HER2 expression levels were used to test the specificity of our functionalized nanoprobe for molecular targeting applications. The results of cell line targeting demonstrate that these engineered MNPs are able to differentiate between cell lines with different levels of HER2 expression.

The effect of functionalized nickel (Ni) nanoparticles capped with positively charged tetraheptylammonium on cellular uptake of drug quercetin into hepatocellular carcinoma cells (SMMC-7721) has been explored in this study via microscopy and electrochemical characterization as well as MTT assay. Meanwhile, the influence of Ni nanoparticles and/or quercetin on cell proliferation has been further evaluated by the real-time cell electronic sensing (RT-CES) study. Our observations indicate that Ni nanoparticles could efficiently improve the permeability of cancer cell membrane, and remarkably enhance the accumulation of quercetin in SMMC-7721 cells, suggesting that Ni nanoparticles and quercetin would facilitate the synergistic effect on inhibiting proliferation of cancer cells.

Fe(3)O(4) nanoparticles were stabilized using different functional polysaccharides, such as chitosan (CS), O-carboxymethylchitosan (OCMCS) and (N-succinyl-O-carboxymethylchitosan (NSOCMCS) to improve their bioactivity. The release profile and the in vitro cancer cell inhibition activity of camptothecin (CPT) loaded polysaccharide modified Fe(3)O(4) nanoparticles were systematically studies. The particle size and size distribution of CPT-loaded polysaccharide modified Fe(3)O(4) nanoparticles were found to be strongly dependent on polysaccharide character. Such polysaccharide character could also affect CPT adsorption efficiency, CPT release behavior and bovine serum albumin (BSA) unspecific binding capacity. After 24 h incubation of 7721 cancer cells with CPT-loaded polysaccharide modified Fe(3)O(4) nanoparticles, significant changes in cell morphology could be discernible from phase contrast microscopy. Cytotoxicity assay showed these polysaccharide modified Fe(3)O(4) nanoparticles did not exhibit noteworthy cytotoxicity against 7721, however, the in vitro inhibition rate of CPT-loaded polysaccharide modified Fe(3)O(4) nanoparticles against 7721 liver cancer cell increased significantly in comparison with that of CPT-free drug.

Maghemite (gamma-Fe2O3) nanoparticles were obtained by the coprecipitation of Fe(II) and Fe (III) salts with ammonium hydroxide followed by oxidation with sodium hypochlorite. Solution radical polymerization of N,N-dimethylacrylamide(DMAAm) in the presence of maghemite nanoparticles yielded poly(N,N-dimethylacrylamide)(PDMAAm)-coated maghemite nanoparticles. The presence of PDMAAm on the maghemite particle surface was confirmed by elemental analysis and ATR FTIR spectroscopy. Other methods of nanoparticle characterization involved scanning and transmission electron microscopy, atomic adsorption spectroscopy (AAS), and dynamic light scattering (DLS). The conversion of DMAAm during polymerization and the molecular weight of PDMAAmbound to maghemite were determined by using gas and size-exclusion chromatography, respectively. The effect of ionic 4,4'-azobis(4-cyanovaleric acid) (ACVA) initiator on nanoparticle morphology was elucidated. The nanoparticles exhibited long-term colloidal stability in water or physiological buffer. Rat and human bone marrow mesenchymal stem cells (MSCs) were labeled with uncoated and PDMAAm-coated maghemite nanoparticles and with Endorem as a control. Uptake of the nanoparticles was evaluated by Prussian Blue staining, transmission electron microscopy, T(2)-MR relaxometry, and iron content analysis. Significant differences in labeling efficiency were found for human and rat cells. PDMAAm-modified nanoparticles demonstrated a higher efficiency of intracellular uptake into human cells in comparison with that of dextran-modified (Endorem) and unmodified nanoparticles. In gelatin, even a small number of labeled cells changed the contrast in MR images. PDMAAmcoatednanoparticles provided the highest T(2) relaxivity of all the investigated particles. In vivo MR imaging ofPDMAAm-modified iron oxide-labeled rMSCs implanted in a rat brain confirmed their better resolution compared with Endorem-labeled cells.

The success of cancer chemotherapy is largely dependent on the efficient anticancer drug accumulation in target tumor tissues and cells so as to inhibit the proliferation of the cancer cells. Recently, some biocompatible nanomaterials have been utilized as drug target delivery systems and have shown the great potential to effectively afford the sustained drug delivery for the target cancer cells. In this study, we have explored the possibility for the bio-application of the functionalized nickel (Ni) nanoparticles and the efficiency of the functionalized Ni nanoparticles on drug permeability, and cellular uptake of leukemia K562 cells in vitro has been probed via atomic force microscopy, inverted fluorescence microscopy and confocal microscopy, electrochemical study and MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl-tetrazolium bromide) assay. It is observed that the presence of relevant Ni nanoparticles could induce the membrane structure change of target cells and efficiently improve the permeability of the cell membrane so that the combination of these Ni nanoparticles with anticancer drug daunorubicin could have a synergistic effect on the efficient cytotoxicity suppression in leukemia cancer cells. These observations indicate the great potential of Ni nanoparticles in the future biomedical application including target cancer diagnosis and chemotherapy.