BACKGROUND: Photodynamic therapy (PDT) is a pioneering and effective anticancer modality with low adverse effects and high selectivity. Hypochlorous acid or hypochlorite (HClO/ClO-) is a type of inflammatory cytokine. The abnormal increase of ClO- in tumor cells is related to tumor pathogenesis and may be a \"friend\" for the design and synthesis of responsive phototherapy agents. However, preparing responsive phototherapy agents for all-in-one noninvasive diagnosis and simultaneous in situ therapy in a complex tumor environment is highly desirable but still remains an enormously demanding task.
RESULTS: An acceptor-π bridge-donor-π bridge-acceptor (A-π-D-π-A) type photosensitizer TPTPy was designed and synthesized based on the phenothiazine structure which was used as the donor moiety as well as a ClO- responsive group. TPTPy was a multifunctional mitochondria targeted aggregation-induced emission (AIE) photosensitizer which could quickly and sensitively respond to ClO- with fluorescence \"turn on\" performance (19-fold fluorescence enhancement) and enhanced type I reactive oxygen species (ROS) generation to effectively ablate hypoxic tumor cells. The detection limit of TPTPy to ClO- was calculated to be 185.38 nM. The well-tailored TPTPy anchoring to mitochondria and producing ROS in situ could disrupt mitochondria and promote cell apoptosis. TPTPy was able to image inflammatory cells and tumor cells through ClO- response. In vivo results revealed that TPTPy was successfully utilized for PDT in tumor bearing nude mice and exhibited excellent biological safety for major organs.
UNASSIGNED: A win-win integration strategy was proposed to design a tumor intracellular ClO- responsive photosensitizer TPTPy capable of both type I and type II ROS production to achieve photodynamic therapy of tumor. This work sheds light on the win-win integration design by taking full advantage of the characteristics of tumor microenvironment to build up responsive photosensitizer for in situ PDT of tumor.

This network meta-analysis aims to compare the clinical efficacy of seven non-surgical therapies for peri-implant disease, including laser treatment, photobiomodulation therapy (PBMT), photodynamic therapy (PDT), systemic antibiotics (SA), probiotics, local antimicrobials (LA), and air-powder polishing (APP) combined with mechanical debridement (MD). We conducted searches in four electronic databases, namely PubMed, Embase, Web of Science, and The Cochrane Library, to identify randomized controlled trials of non-surgical treatments combined with MD for individuals (aged at least 18 years) diagnosed with peri-implantitis or peri-implant mucositis with a minimum of 3 months follow-up. The outcomes of the study were the reduction in pocket probing depth (PPD) and bleeding on probing (BoP), plaque index (PLI), clinical attachment level (CAL), and marginal bone loss (MBL). We employed a frequency random effects network meta-analysis model to combine the effect sizes of the trials using standardized mean difference (SMD) and 95% confidence intervals (CIs). Network meta-analyses include network plots, paired comparison forest plots, league tables, funnel plots, surface under the cumulative ranking area (SUCRA) plots, and sensitivity analysis plots. The results showed that, for peri-implantitis, PBMT +MD demonstrated the highest effect in improving PPD (SUCRA = 75.3%), SA +MD showed the highest effect in improving CAL (SUCRA = 87.4%, SMD = 2.20, and 95% CI: 0.38 to 4.02) and MBL (SUCRA = 99.9%, SMD = 3.92, and 95% CI. 2.90 to 4.93), compared to MD alone. For peri-implant mucositis, probiotics +MD demonstrated the highest effect in improving PPD (SUCRA = 100%) and PLI (SUCRA = 83.2%), SA +MD showed the highest effect in improving BoP (SUCRA = 88.1%, SMD = 0.77, and 95% CI: 0.27 to 1.28), compared to MD alone. Despite the ranking established by our study in the treatment of peri-implant disease, decisions should still be made with reference to the latest treatment guidelines. There is still a need for more high-quality studies to provide conclusive evidence and especially a need for studies regarding direct comparisons between multiple treatment options.

Nanobodies (Nbs), the smallest antigen-binding fragments with high stability and affinity derived from the variable domain of naturally occurring heavy-chain-only antibodies in camelids, have been shown as an efficient way to improve the specificity to tumors for photodynamic therapy (PDT). Nonetheless, the rapid clearance of Nbs in vivo restricts the accumulation and retention of the photosensitizer at the tumor site causing insufficient therapeutic outcome, especially in large-volume tumors. Herein, we develop photodynamic conjugates, MNB-Pyra Nbs, through site-specific conjugation between 7D12 Nbs and type I photosensitizer MNB-Pyra (morpholine-modified nile blue structure connected to pyrazolinone) in a 1:2 ratio. The photosensitizers with long-term retention can be released at the tumor site by reactive oxygen species cleavage after illumination, accompanied with fluorescence recovery for self-reporting the occurrence of PDT. Ultimately, a single dose of MNB-Pyra Nbs demonstrate highly effective tumor suppression with high biosafety in the large-volume tumor models after three rounds of PDT. This nanobody conjugate provides a paradigm for the design of precise long-time retention photosensitizers and is expected to promote the development of PDT.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly malignant tumor known for its hypoxic environment, which contributes to resistance against the anticancer drug Sorafenib (SF). Addressing SF resistance in HCC requires innovative strategies to improve tumor oxygenation and effectively deliver therapeutics.
RESULTS: In our study, we explored the role of KPNA4 in mediating hypoxia-induced SF resistance in HCC. We developed hemoglobin nanoclusters (Hb-NCs) capable of carrying oxygen, loaded with indocyanine green (ICG) and SF, named HPRG@SF. In vitro, HPRG@SF targeted HCC cells, alleviated hypoxia, suppressed KPNA4 expression, and enhanced the cytotoxicity of PDT against hypoxic, SF-resistant HCC cells. In vivo experiments supported these findings, showing that HPRG@SF effectively improved the oxygenation within the tumor microenvironment and countered SF resistance through combined photodynamic therapy (PDT).
CONCLUSIONS: The combination of Hb-NCs with ICG and SF, forming HPRG@SF, presents a potent strategy to overcome drug resistance in hepatocellular carcinoma by improving hypoxia and employing PDT. This approach not only targets the hypoxic conditions that underlie resistance but also provides a synergistic anticancer effect, highlighting its potential for clinical applications in treating resistant HCC.

UNASSIGNED: Chemotherapy mediated by Reactive oxygen species (ROS)-responsive drug delivery systems can potentially mitigate the toxic side effects of chemotherapeutic drugs and significantly enhance their therapeutic efficacy. However, achieving precise targeted drug delivery and real-time control of ROS-responsive drug release at tumor sites remains a formidable challenge. Therefore, this study aimed to describe a ROS-responsive drug delivery system with specific tumor targeting capabilities for mitigating chemotherapy-induced toxicity while enhancing therapeutic efficacy under guidance of Fluorescence (FL) and Magnetic resonance (MR) bimodal imaging.
UNASSIGNED: Indocyanine green (ICG), Doxorubicin (DOX) prodrug pB-DOX and Superparamagnetic iron oxide (SPIO, Fe3O4) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) by double emulsification method to prepare ICG/ pB-DOX/ Fe3O4/ PLGA nanoparticles (IBFP NPs). The surface of IBFP NPs was functionalized with mammaglobin antibodies (mAbs) by carbodiimide method to construct the breast cancer-targeting mAbs/ IBFP NPs (MIBFP NPs). Thereafter, FL and MR bimodal imaging ability of MIBFP NPs was evaluated in vitro and in vivo. Finally, the combined photodynamic therapy (PDT) and chemotherapy efficacy evaluation based on MIBFP NPs was studied.
UNASSIGNED: The multifunctional MIBFP NPs exhibited significant targeting efficacy for breast cancer. FL and MR bimodal imaging clearly displayed the distribution of the targeting MIBFP NPs in vivo. Upon near-infrared laser irradiation, the MIBFP NPs loaded with ICG effectively generated ROS for PDT, enabling precise tumor ablation. Simultaneously, it triggered activation of the pB-DOX by cleaving its sensitive moiety, thereby restoring DOX activity and achieving ROS-responsive targeted chemotherapy. Furthermore, the MIBFP NPs combined PDT and chemotherapy to enhance the efficiency of tumor ablation under guidance of bimodal imaging.
UNASSIGNED: MIBFP NPs constitute a novel dual-modality imaging-guided drug delivery system for targeted breast cancer therapy and offer precise and controlled combined treatment options.

The spread of multidrug-resistant mycobacterium strains requires the development of new approaches to combat diseases caused by these pathogens. For that, photodynamic inactivation (PDI) is a promising approach. In this study, a tricarbocyanine (TCC) is used for the first time as a near-infrared (740 nm) activatable PDI photosensitizer to kill mycobacteria with deep light penetration. For better targeting, a novel tricarbocyanine dye functionalized with two trehalose units (TCC2Tre) is developed. The photodynamic effect of the conjugates against mycobacteria, including Mycobacterium tuberculosis, is evaluated. Under irradiation, TCC2Tre causes more effective killing of mycobacteria compared to the photosensitizer without trehalose conjugation, with 99.99% dead vegetative cells of M. tuberculosis and M. smegmatis. In addition, effective photoinactivation of dormant forms of M. smegmatis is observed after incubation with TCC2Tre. Mycobacteria treated with TCC2Tre are more sensitive to 740 nm light than the Gram-positive Micrococcus luteus and the Gram-negative Escherichia coli. For the first time, this study demonstrates the proof of principle of in vitro PDI of mycobacteria including the fast-growing M. smegmatis and the slow-growing M. tuberculosis using near-infrared activatable photosensitizers conjugated with trehalose. These findings are useful for the development of new efficient alternatives to antibiotic therapy.

Over the past decades, medicine has made enormous progress, revolutionized by modern technologies and innovative therapeutic approaches. One of the most exciting branches of these developments is photodynamic therapy (PDT). Using a combination of light of a specific wavelength and specially designed photosensitizing substances, PDT offers new perspectives in the fight against cancer, bacterial infections, and other diseases that are resistant to traditional treatment methods. In today\'s world, where there is a growing problem of drug resistance, the search for alternative therapies is becoming more and more urgent. Imagine that we could destroy cancer cells or bacteria using light, without the need to use strong chemicals or antibiotics. This is what PDT promises. By activating photosensitizers using appropriately adjusted light, this therapy can induce the death of cancer or bacterial cells while minimizing damage to surrounding healthy tissues. In this work, we will explore this fascinating method, discovering its mechanisms of action, clinical applications, and development prospects. We will also analyze the latest research and patient testimonies to understand the potential of PDT for the future of medicine.

Oral candidiasis is a common problem among immunocompetent patients. The frequent resistance of Candida strains to popular antimycotics makes it necessary to look for alternative methods of treatment. The authors conducted a systematic review following the PRISMA 2020 guidelines. The objective of this review was to determine if curcumin-mediated blue light could be considered as an alternative treatment for oral candidiasis. PubMed, Google Scholar, and Cochrane Library databases were searched using a combination of the following keywords: (Candida OR candidiasis oral OR candidiasis oral OR denture stomatitis) AND (curcumin OR photodynamic therapy OR apt OR photodynamic antimicrobial chemotherapy OR PACT OR photodynamic inactivation OR PDI). The review included in vitro laboratory studies with Candida spp., in vivo animal studies, and randomized control trials (RCTs) involving patients with oral candidiasis or prosthetic stomatitis, published only in English. The method of elimination of Candida species in the studies was curcumin-mediated aPDT. A total of 757 studies were identified. Following the analysis of the titles and abstracts of the studies, only 42 studies were selected for in-depth screening, after which 26 were included in this study. All studies evaluated the antifungal efficacy of curcumin-mediated aPDT against C. albicans and non-albicans Candida. In studies conducted with planktonic cells solutions, seven studies demonstrated complete elimination of Candida spp. cells. The remaining studies demonstrated only partial elimination. In all cases, experiments on single-species yeast biofilms demonstrated partial, statistically significant inhibition of cell growth and reduction in biofilm mass. In vivo, curcumin-mediated aPDT has shown good antifungal activity against oral candidiasis also in an animal model. However, its clinical efficacy as a potent therapeutic strategy for oral candidiasis requires few further RCTs.

Graphene Quantum Dots (GQDs) have shown the potential for antimicrobial photodynamic treatment, due to their particular physicochemical properties. Here, we investigated the activity of three differently functionalized GQDs-Blue Luminescent GQDs (L-GQDs), Aminated GQDs (NH2-GQDs), and Carboxylated GQDs (COOH-GQDs)-against E. coli. GQDs were administrated to bacterial suspensions that were treated with blue light. Antibacterial activity was evaluated by measuring colony forming units (CFUs) and metabolic activities, as well as reactive oxygen species stimulation (ROS). GQD cytotoxicity was then assessed on human colorectal adenocarcinoma cells (Caco-2), before setting in an in vitro infection model. Each GQD exhibits antibacterial activity inducing ROS and impairing bacterial metabolism without significantly affecting cell morphology. GQD activity was dependent on time of exposure to blue light. Finally, GQDs were able to reduce E. coli burden in infected Caco-2 cells, acting not only in the extracellular milieu but perturbating the eukaryotic cell membrane, enhancing antibiotic internalization. Our findings demonstrate that GQDs combined with blue light stimulation, due to photodynamic properties, have a promising antibacterial activity against E. coli. Nevertheless, we explored their action mechanism and toxicity on epithelial cells, fixing and standardizing these infection models.

Photothermal, photodynamic and sonodynamic cancer therapies offer opportunities for precise tumor ablation and reduce side effects. The cyclic guanylate adenylate synthase-stimulator of interferon genes (cGAS-STING) pathway has been considered a potential target to stimulate the immune system in patients and achieve a sustained immune response. Combining photothermal, photodynamic and sonodynamic therapies with cGAS-STING agonists represents a newly developed cancer treatment demonstrating noticeable innovation in its impact on the immune system. Recent reviews have concentrated on diverse materials and their function in cancer therapy. In this review, we focus on the molecular mechanism of photothermal, photodynamic and sonodynamic cancer therapies and the connected role of cGAS-STING agonists in treating cancer.