Glucose oxidase (GOx) with unique catalytic properties and inherent biocompatibility can effectively oxidize both endogenous and exogenous glucose with oxygen (O2) into gluconic acid and hydrogen peroxide (H2O2). Accordingly, the GOx-based catalytic chemistry offers new possibilities for designing and constructing multimodal synergistic antibacterial systems. The consumption of glucose permanently downregulates bacterial cell metabolism by blocking essential energy supplies, inhibiting their growth and survival. Additionally, the production of gluconic acid could downregulates the pH within the bacterial infection microenvironment, enhancing the production of hydroxyl radicals (∙OH) from H2O2 via enhanced Fenton or Fendon-like reactions and triggering the pH-responsive release of drugs. Furthermore, the generated H2O2 in situ avoids the addition of exogenous hydrogen peroxide. Therefore, it is possible to design GOx-based multimodal antibacterial synergistic therapies by combining GOx-instructed cascade reactions with other therapeutic approaches such as chemodynamic therapies (CDT), hypoxia-activated prodrugs, photosensitizers, and stimuli-responsive drug release. Such multimodal strategies are expected to exhibit better therapeutic effects than single therapeutic modes. This tutorial review highlights recent advancements in GOx-instructed multimodal synergistic antibacterial systems, focusing on design philosophy and construction strategies. Current challenges and future prospects for advancing GOx-based multimodal antibacterial synergistic therapies are discussed.

Conjugated polymers (CPs) have emerged as promising candidates for photodynamic therapy (PDT) in cancer treatment due to their high fluorescence quantum yield, excellent photostability, and remarkable reactive oxygen species (ROS) generation capability. This review systematically summarizes molecular design strategies to augment CP photosensitivity efficiency, including: (1) constructing donor-acceptor (D-A) alternating structures, (2) incorporating aggregation-induced emission (AIE) moieties, (3) employing heavy-atom effects, and (4) designing hyperbranched architectures. In addition, considering the limitations of monotherapy like tumor heterogeneity, we will further discuss the synergistic treatment strategies of CP-mediated PDT in combination with other therapeutic modalities, including photothermal therapy (PTT)-PDT, immunotherapy-PDT, chemotherapy-PDT, Chemiluminescence (CL)-PDT, diagnostic technology-PDT, and chemodynamic therapy (CDT)-PDT. These multimodal approaches leverage complementary mechanisms to achieve enhanced tumor eradication efficacy.

Thiophene and pyrrole units are extensively utilized in light-responsive materials and have significantly advanced the field of organic photovoltaics (OPV). This progress has inspired our exploration of photosensitizers (PS) for photodynamic therapy (PDT). Currently, traditional PS face limitations in clinical application, including a restricted variety and narrow applicability. Drawing upon molecular design concepts from OPV, we aim to transcend these limitations in PDT. Given the abundance of candidate molecules, effective screening is crucial. Theoretical calculations and electronic structure analyses serve as precise and practical screening methods. In this study, we adopted strategies successfully employed in OPV molecular design, focusing on donor-acceptor (D-A) and acceptor-donor-acceptor (A-D-A) structures. Using density functional theory (DFT) and time-dependent density functional theory (TDDFT), we systematically designed combinations of promising organic fragments. These fragments include polythiophene and polypyrrole-dominated donor structures, paired with five electron acceptors: indene (Ind), diketopyrrole (DPP), naphthalimide (Ni), benzothiazole (Btd), and dithiazolyl diketopyrrole (Tbo). Through meticulous calculations, we obtained electronic structures and spectral properties for all candidate molecules, facilitating an efficient screening process. Our findings highlight that those combinations of polypyrrole-based frameworks with DPP, Ni, and Btd show significant promise for PS applications. Approximately 13% of candidates were selected through comprehensive comparison, markedly reducing molecular design time and experimental costs. This interdisciplinary approach holds potential to pave the way for more targeted and successful PS designs.

Glioblastoma (GBM) is one of the most lethal human malignancies. The current standard-of-care is highly invasive with strong toxic side effects, leading to poor prognosis and high mortality. As a safe and effective clinical approach, photodynamic therapy (PDT) has emerged as a suitable option for GBM. Nevertheless, its implementation is significantly impeded by the limits of light penetration depth and the firm reliance on oxygen. To overcome these challenges, herein, a promising strategy that harnesses a modified optical fiber and less oxygen-dependent Type I aggregation-induced emission (AIE) photosensitizer (PS) is developed for the first time to realize in vivo GBM treatments. The proposed AIE PS, namely TTTMN, characterized by a highly twisted molecular architecture and a bulky spacer, exhibits enhanced near-infrared emission and strong production of hydroxyl and superoxide radicals at the aggregated state, thus affording efficient fluorescence imaging-guided PDT once formulated into nanoparticles. The inhibition of orthotopic and subcutaneous GBM xenografts provides compelling evidence of the treatment efficacy of Type I PDT irradiated through a tumor-inserted optical fiber. These findings highlight the substantially improved therapeutic outcomes achieved through fiber optic-mediated Type I PDT, positioning it as a promising therapeutic modality for GBM.

Chitosan, a naturally occurring biopolymer derived from chitin, has emerged as a highly promising instrument for the production and application of metal nanoparticles. The present review delves into the several functions of chitosan in the development and operation of metal nanoparticles, emphasizing its aptitudes as a green reducing agent, shape-directing agent, size-controlling agent, and stabilizer. Chitosan's special qualities make it easier to manufacture metal nanoparticles and nanocomposites with desired characteristics. Furthermore, there is a lot of promise for chitosan-based nanocomposites in a number of fields, such as metal removal, water purification, and photoacoustic, photothermal, antibacterial, and photodynamic therapies. This thorough analysis highlights the potential application of chitosan in the advancement of nanotechnology and the development of medicinal and environmental solutions.

The increasing incidence of breast cancers (BCs) in the world population and their complexity and high metastatic ability are serious concerns for healthcare systems. Despite the significant progress in medicine made in recent decades, the efficient treatment of invasive cancers still remains challenging. Chemotherapy, a fundamental systemic treatment method, is burdened with severe adverse effects, with efficacy limited by resistance development and risk of disease recurrence. Also, current diagnostic methods have certain drawbacks, attracting attention to the idea of developing novel, more sensitive detection and therapeutic modalities. It seems the solution for these issues can be provided by nanotechnology. Particularly, quantum dots (QDs) have been extensively evaluated as potential targeted drug delivery vehicles and, simultaneously, sensing and bioimaging probes. These fluorescent nanoparticles offer unlimited possibilities of surface modifications, allowing for the attachment of biomolecules, such as antibodies or proteins, and drug molecules, among others. In this work, we discuss the potential applicability of QDs in breast cancer diagnostics and treatment in light of the current knowledge. We begin with introducing the molecular and histopathological features of BCs, standard therapeutic regimens, and current diagnostic methods. Further, the features of QDs, along with their uptake, biodistribution patterns, and cytotoxicity, are described. Based on the reports published in recent years, we present the progress in research on possible QD use in improving BC diagnostics and treatment efficacy as chemotherapeutic delivery vehicles and photosensitizing agents, along with the stages of their development. We also address limitations and open questions regarding this topic.

Obesity and its associated hepatic steatosis have become a global concern, posing numerous health hazards. Photodynamic therapy (PDT) is a unique approach that promotes anti-obesity by releasing intracellular fat. Chlorin e6 (Ce6)-PDT was tested for its anti-obesity properties in male ovariectomized (OVX) beagle dogs, as well as male C57BL/6 and Balb/c mice. The 12 OVX beagles were randomly assigned to one of four groups: high-fat diet (HFD) only, Ce6 only, Ce6 + 10 min of light-emitting diode light (LED) treatment, and Ce6 + 15 min of light treatment. We assessed several parameters, such as body weight, adipose tissue morphology, serum biochemistry, and body fat content analysis by computed tomography (CT) scan in HFD-fed beagle dogs. At the end of the study period, dogs that were treated for 35 days with Ce6 and exposed to LED irradiation (660 nm) either for 10 min (Ce6 + 10 min of light) or for 15 min (Ce6 + 15 min of light) had decreased body weight, including visceral and subcutaneous fats, lower aspartate transaminase (AST)/alanine transaminase (ALT) ratios, and a reduction in the area of individual adipocytes with a concomitant increase in the number of adipocytes. Furthermore, C57BL/6 male mice following an HFD diet were effectively treated by Ce6-PDT treatment through a reduction in weight gain and fat accumulation. Meanwhile, Ce6-PDT attenuated hepatocyte steatosis by decreasing the epididymal adipose tissue and balloon degeneration in hepatocytes in HFD-fed Balb/c mice. Taken together, our results support the idea that Ce6-PDT is a promising therapeutic strategy for the recovery of obesity and obesity-related hepatic steatosis.

As the risk of antibiotic-resistant bacteria increases, interest in non-antibiotic treatment is also increasing. Among the methods used in non-antibiotic therapy, natural antibiotics such as essential oils have disadvantages such as low efficiency. In the case of phototherapy, the light used for antibacterial activities has low penetration into the human body because of its short wavelength, making it of low medical utility. To solve this problem, this study aimed to determine conditions for enhancing the antibacterial activity of natural phytochemicals and visible light. Four natural phytochemical extracts that showed high antibacterial properties in previous studies were analyzed. Synergistic effects on antibacterial activity and cytotoxicity were determined when natural phytochemical extracts and visible light were simultaneously used. As a result, it was confirmed that the antibacterial activity increased by four times when Sanguisorba officinalis L. was irradiated with 465 nm for 10 min and 520 nm for 40 min, and Uncaria gambir Roxb. was irradiated with 465 nm for 10 min and 520 nm for 60 min compared to when Sanguisorba officinalis L. and Uncaria gambir Roxb. were used alone. The synergistic effect on antibacterial activity was independent of the absorption peak of the natural phytochemical extracts. In addition, in the case of natural phytochemical extracts with improved antibacterial activity, it was confirmed that the improvement of antibacterial activity was increased in inverse proportion to the light irradiation wavelength and in proportion to the light irradiation time. The antibacterial activity was enhanced regardless of antibiotic resistance. In the case of cytotoxicity, it was confirmed that there was no toxicity to A549 cells when treated with 465 nm, the shortest wavelength among the natural phytochemical extracts. These results show how to replace blue light, which has been underutilized due to its low transmittance and cytotoxicity. They also demonstrate the high medical potential of using natural phytochemical and visible light as a combination therapy.

Photodynamic therapy (PDT) can take place in the presence of three elements: Light with an appropriate wavelength; a photosensitizer; and the presence of oxygen. This type of treatment is very effective overall against bacterial, viral and mycotic cells. In the last 10 years many papers have been published on PDT with different types of photosensitizers (e.g., methylene blue, toluidine blue, indocyanine green, curcumin-based photosensitizers), different wavelengths (e.g., 460 nm, 630 nm, 660 nm, 810 nm) and various parameters (e.g., power of the light, time of illumination, number of sessions). In the scientific literature all types of PDT seem very effective, even if it is difficult to find a standard protocol for each oral pathology. PDT could be an interesting way to treat some dangerous oral infections refractory to common pharmacological therapies, such as candidiasis from multidrug-resistant Candida spp.

A biofilm is a collection of microorganisms organized in a matrix of extracellular polymeric material. Biofilms consist of microbial cells that attach to both surfaces and each other, whether they are living or non-living. These microbial biofilms can lead to hospital-acquired infections and are generally detrimental. They possess the ability to resist the human immune system and antibiotics. The National Institute of Health (NIH) states that biofilm formation is associated with 65% of all microbial illnesses and 80% of chronic illnesses. Additionally, non-device-related microbial biofilm infections include conditions like cystic fibrosis, otitis media, infective endocarditis, and chronic inflammatory disorders. This review aims to provide an overview of research on chronic infections caused by microbial biofilms, methods used for biofilm detection, recent approaches to combat biofilms, and future perspectives, including the development of innovative antimicrobial strategies such as antimicrobial peptides, bacteriophages, and agents that disrupt biofilms.

Oral squamous cell carcinoma (OSCC) is a type of cancer that is responsible for a significant amount of morbidity and mortality worldwide. Researchers are searching for promising therapeutic methods to manage this cancer. In this study, an in silico approach was used to evaluate the activity of sonodynamic therapy (SDT) based on the use of Kojic acid as a sonosensitizer to inhibit matrix metalloprotease-9 (MMP-9) in OSCC.

The three-dimensional structure of MMP-9 was predicted and validated by computational approaches. The possible functional role of MMP-9 was determined in terms of Gene Ontology (GO) enrichment analysis. In silico, molecular docking was then performed to evaluate the binding energies of Kojic acid with MMP-9, and ADME parameters and toxicity risks were predicted. The pharmacokinetics and drug-likeness properties of Kojic acid were assessed. Moreover, after the determination of the cytotoxicity effect of Kojic acid-mediated SDT, the change of mmp-9 gene expression was assessed on OSCC cells.

The results of the study showed that Kojic acid could efficiently interact with MMP-9 protein with a strong binding affinity. Kojic acid obeyed Lipinski's rule of five without violation and exhibited drug-likeness. The cytotoxic effects of Kojic acid and ultrasound waves on the OSCC cells were dose-dependent, and the lowest expression level of the mmp-9 gene was observed in SDT.

Overall, Kojic acid-mediated SDT as an MMP-9 inhibitor can be a promising adjuvant treatment for OSCC. The study highlights the potential of In silico approaches to evaluate therapeutic methods for cancer treatment.

Skin color affects light penetration leading to differences in its absorption and scattering properties. COVID-19 highlighted the importance of understanding of the interaction of light with different skin types, e.g., pulse oximetry (PO) unreliably determined oxygen saturation levels in people from Black and ethnic minority backgrounds. Furthermore, with increased use of other medical wearables using light to provide disease information and photodynamic therapies to treat skin cancers, a thorough understanding of the effect skin color has on light is important for reducing healthcare disparities.

The aim of this work is to perform a thorough review on the effect of skin color on optical properties and the implication of variation on optical medical technologies.

Published in vivo optical coefficients associated with different skin colors were collated and their effects on optical penetration depth and transport mean free path (TMFP) assessed.

Variation among reported values is significant. We show that absorption coefficients for dark skin are ∼ 6 % to 74% greater than for light skin in the 400 to 1000 nm spectrum. Beyond 600 nm, the TMFP for light skin is greater than for dark skin. Maximum transmission for all skin types was beyond 940 nm in this spectrum. There are significant losses of light with increasing skin depth; in this spectrum, depending upon Fitzpatrick skin type (FST), on average 14% to 18% of light is lost by a depth of 0.1 mm compared with 90% to 97% of the remaining light being lost by a depth of 1.93 mm.

Current published data suggest that at wavelengths beyond 940 nm light transmission is greatest for all FSTs. Data beyond 1000 nm are minimal and further study is required. It is possible that the amount of light transmitted through skin for all skin colors will converge with increasing wavelength enabling optical medical technologies to become independent of skin color.

Photodynamic therapy is an alternative treatment for several pathologies, including cancer. This therapy uses a photosensitizer capable of producing reactive oxygen species through irradiation, promoting cellular death. A limitation of photosensitizers is their low solubility in aqueous media. Hence, developing a suitable carrier for photosensitizers for specific applications is a challenge. Cervical cancer is one of the most common cancers in women, and photodynamic therapy could be an attractive alternative therapeutic approach. In this work, we synthesized films composed of chitosan, polyvinylpyrrolidone, and liposomes containing Zn-phthalocyanine. Photophysical characterization of ZnPc incorporated into films was determined by UV-vis and fluorescence. Film properties such as swelling, mechanical properties, and water vapor permeability were performed. Finally, in vitro, photodynamic evaluation of these films was performed on HeLa cells. The results indicate that incorporating Zn-Pc-liposomes into films decreases cell viability by >95 %.

Photodynamic Therapy (PDT) is an effective tumor treatment strategy that not only induces photocytotoxicity to kill tumor cells directly but also activates the immune system in the body to generate tumor-specific immunity, preventing cancer metastasis and recurrence. However, some limitations of PDT limit the therapeutic efficacy in deep tumors. Previous studies have used different types of nanoparticles (NPs) as drug carriers of photosensitizers (PSs) to overcome the shortcomings of PDT and improve therapeutic efficacy. Among them, bacterial outer membrane vesicles (OMVs) have natural advantages as carriers for PS delivery. In addition to the targeted delivery of PSs into tumor cells, their unique immunogenicity helps them to serve as immune adjuvants to enhance the PDT-induced immune effect, providing new ideas for photodynamic anticancer therapy. Therefore, in this review, we will introduce the biogenesis and anticancer functions of OMVs and the research on them as drug delivery carriers in PDT. Finally, we also discuss the challenges and prospects of OMVs as a versatile drug delivery carrier for photodynamic anticancer therapy.

A supramolecular redox responsive nanogel (NG) with the ability to sense cancer cells and loaded with a releasing therapeutic agent was synthesized using hostguest interactions between polyethylene glycol-grafted-β-cyclodextrin and ferrocene boronic acid. Cyclic voltammetry matched with other spectroscopy and microscopy methods provided strong indications regarding host-guest interactions and formation of the NG. Moreover, the biological properties of the NG were evaluated using fluorescence silencing, confocal laser scanning microscopy, and cell toxicity assays. Nanogel with spherical core-shell architecture and 100-200 nm sized nanoparticles showed high encapsulation efficiency for doxorubicin (DOX) and luminol (LU) as therapeutic and sensing agents. High therapeutic and sensing efficiencies were manifested by complete release of DOX and dramatic quenching of LU fluorescence triggered by 0.05 mM H2O2 (as an ROS component). The NGs showed high ROS sensitivity. Taking advantage of a high loading capacity, redox sensitivity, and biocompatibility, the NGs can be used as strong theranostic systems in inflammation-associated diseases.

Given that light is hard to reach deep tumor tissue, how to enhance photodynamic therapy (PDT) efficacy is a big challenge. Herein, we proposed the supramolecular polymer self-assemblies (HACP) with bis[2,4,5-trichloro-6 (pentyloxycar-bonyl) phenyl] oxalate as the cargos (HACP@CPPO) to realize the chemiluminescence resonance energy transfer (CRET)-induced generation of 1O2 in situ. HACP was prepared by cinnamaldehyde-modified hyaluronic acid (HA-CA) and β-cyclodextrin-modified protoporphyrin IX (β-CD-PPIX) via host-guest interactions. The CA moiety could elevate H2O2 levels for the enhanced production of chemical energy and macrocyclic CD could enhance the stacking distance of PPIX for enhanced 1O2 yield. Thus, HACP@CPPO exhibited excellent antitumor performance without light irradiation.

Malocclusion is one of the three major diseases, the incidence of which could reach 56% of the imperiled oral and systemic health in the world today. Orthodontics is still the primary method to solve the problem. However, it is clear that many orthodontic complications are associated with courses of long-term therapy. Photobiomodulation (PBM) therapy could be used as a popular way to shorten the course of orthodontic treatment by nearly 26% to 40%. In this review, the efficacy in cells and animals, mechanisms, relevant cytokines and signaling, clinical trials and applications, and the future developments of PBM therapy in orthodontics were evaluated to demonstrate its validity. Simultaneously, based on orthodontic mechanisms and present findings, the mechanisms of acceleration of orthodontic tooth movement (OTM) caused by PBM therapy were explored in relation to four aspects, including blood vessels, inflammatory response, collagen and fibers, and mineralized tissues. Also, the cooperative effects and clinical translation of PBM therapy in orthodontics have been explored in a growing numbers of studies. Up to now, PBM therapy has been gaining popularity for its non-invasive nature, easy operation, and painless procedures. However, the validity and exact mechanism of PBM therapy as an adjuvant treatment in orthodontics have not been fully elucidated. Therefore, this review summarizes the efficacy of PBM therapy on the acceleration of OTM comprehensively from various aspects and was designed to provide an evidence-based platform for the research and development of light-related orthodontic tooth movement acceleration devices.

Photodynamic therapy, an alternative that has gained weight and popularity compared to current conventional therapies in the treatment of cancer, is a minimally invasive therapeutic strategy that generally results from the simultaneous action of three factors: a molecule with high sensitivity to light, the photosensitizer, molecular oxygen in the triplet state, and light energy. There is much to be said about each of these three elements; however, the efficacy of the photosensitizer is the most determining factor for the success of this therapeutic modality. Porphyrins, chlorins, phthalocyanines, boron-dipyrromethenes, and cyanines are some of the N-heterocycle-bearing dyes' classes with high biological promise. In this review, a concise approach is taken to these and other families of potential photosensitizers and the molecular modifications that have recently appeared in the literature within the scope of their photodynamic application, as well as how these compounds and their formulations may eventually overcome the deficiencies of the molecules currently clinically used and revolutionize the therapies to eradicate or delay the growth of tumor cells.

Multidrug-resistant (MDR) bacteria are rapidly emerging, coupled with the failure of current antibiotic therapy; thus, new alternatives for effectively treating infections caused by MDR bacteria are required. Hyperthermia-mediated photothermal therapy (PTT) and reactive oxygen species (ROS)-mediated photodynamic therapy (PDT) have attracted extensive attention as antibacterial therapies owing to advantages such as low invasiveness, low toxicity, and low likelihood of causing bacterial resistance. However, both strategies have notable drawbacks, including the high temperature requirements of PTT and the weak ability of PDT-derived ROS to penetrate target cells. To overcome these limitations, a combination of PTT and PDT has been used against MDR bacteria. In this review, we discuss the unique benefits and limitations of PTT and PDT against MDR bacteria. The mechanisms underlying the synergistic effects of the PTT-PDT combination are also discussed. Furthermore, we introduced advancements in antibacterial methods using nano-based PTT and PDT agents to treat infections caused by MDR bacteria. Finally, we highlight the existing challenges and future perspectives of synergistic PTT-PDT combination therapy against infections caused by MDR bacteria. We believe that this review will encourage synergistic PTT- and PDT-based antibacterial research and can be referenced for future clinical applications.

Marine Coelenterazine is one of the most well-known chemi-/bioluminescent systems, and in which reaction the chemi-/bioluminophore (Coelenteramide) is generated and chemiexcited to singlet excited states (leading to light emission). Recent studies have shown that the bromination of compounds associated with the marine Coelenterazine system can provide them with new properties, such as anticancer activity and enhanced emission. Given this, our objective is to characterize the photophysical properties of a previously reported brominated Coelenteramide analog, by employing a combined experimental and theoretical approach. To better analyze the potential halogen effect, we have also synthesized and characterized, for the first time, two new fluorinated and chlorinated Coelenteramide analogs. These compounds show similar emission spectra in aqueous solution, but with different fluorescence quantum yields, in a trend that can be correlated with the heavy-atom effect (F > Cl > Br). A blue shift in emission in other solvents is also verified with the F−Cl−Br trend. More relevantly, the fluorescence quantum yield of the brominated analog is particularly sensitive to changes in solvent, which indicates that this compound has potential use as a microenvironment fluorescence probe. Theoretical calculations indicate that the observed excited state transitions result from local excitations involving the pyrazine ring. The obtained information should be useful for the further exploration of halogenated Coelenteramides and their luminescent properties.