The impact of photodynamic therapy on immune system in cancer – an update

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 28, 2024

Photodynamic therapy (PDT) is a therapeutic approach that has gained significant attention in recent years with its promising impact on the immune system. Recent studies have shown PDT can modulate both innate and adaptive arms of Currently, numerous clinical trials are underway to investigate effectiveness this method treating various types cancer, as well evaluate system cancer treatment. Notably, demonstrated recruitment activation cells, including neutrophils, macrophages, dendritic at treatment site following PDT. Moreover, combination approaches involving immunotherapy also been explored trials. Despite advancements technological development, further needed fully uncover mechanisms underlying by The main objective review comprehensively summarize discuss ongoing completed response.

Language: Английский

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Mechanistic insights into Rho/MRTF inhibition-induced apoptotic events and prevention of drug resistance in melanoma: implications for the involvement of pirin

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 23, 2025

Aim Overcoming therapy resistance is critical for effective melanoma control. Upregulation of Rho/MRTF signaling in human and mouse melanomas causes to targeted therapies. Inhibition this pathway by MRTFi, CCG-257081 resensitized resistant BRAF MEK inhibitors. It also prevented the development vemurafenib (Vem). Here, we investigate role apoptosis protein pirin CCG-257081-mediated suppression drug resistance. Methods Using naïve YUMMER cells, studied effect inhibitor Vem with or without on real-time growth (activation caspase, Propidium iodide (PI) staining, PARP cleavage). The effects proliferation (Ki67) caspase-3 activation were assessed YUMMER_R tumors vivo . Finally, two enantiomers tested binding, inhibition Rho/MRTF-mediated ACTA2 gene expression fibroblasts, prevention YUMMER_P cells. Results reduced parental but not while inhibited both. combination was more than alone. CCG-257081, Vem, induced -7 cells increased cleavage PI staining. activated tumors. Both robustly suppressed Vem-resistant colonies S isomer being potent (1 μM IC 50 ). Conclusion appears target pre-resistant Vem-induced through enhanced apoptosis. can be employed prevent

Language: Английский

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Near‐Infrared‐II Nanoparticles for Vascular Normalization Combined with Immune Checkpoint Blockade via Photodynamic Immunotherapy Inhibit Uveal Melanoma Growth and Metastasis

Advanced Science, Journal Year: 2023, Volume and Issue: 10(35)

Published: Nov. 8, 2023

Abstract Photodynamic therapy (PDT) has been widely employed in tumor treatment due to its effectiveness. However, the hypoxic microenvironment which is caused by abnormal vasculature severely limits efficacy of PDT. Furthermore, implicated failure immunotherapy. In this study, a novel nanoparticle denoted as Combo‐NP introduced, composed biodegradable NIR II fluorescent pseudo‐conjugate polymer featuring disulfide bonds within main chain, designated TPA‐BD, and vascular inhibitor Lenvatinib. exhibits dual functionality not only inducing cytotoxic reactive oxygen species (ROS) directly eliminate cells but also eliciting immunogenic cell death (ICD). This ICD response, turn, initiates robust cascade immune reactions, thereby augmenting generation T lymphocytes (CTLs). addition, addresses issue hypoxia normalizing vasculature. normalization process enhances PDT while concurrently fostering increased CTLs infiltration microenvironment. These synergistic effects synergize potentiate photodynamic‐immunotherapeutic properties nanoparticles. when combined with anti‐programmed death‐ligand 1 (PD‐L1), they showcase notable inhibitory on metastasis. The findings study introduce an innovative nanomedicine strategy aimed at triggering systemic anti‐tumor responses for Uveal melanoma.

Language: Английский

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A review on the chemistry and pharmacological properties of benzodiazepine motifs in drug design

Arab Journal of Basic and Applied Sciences, Journal Year: 2022, Volume and Issue: 29(1), P. 287 - 306

Published: Aug. 30, 2022

Benzodiazepines are an important class of heterocyclic compounds in organic chemistry. They known for their diverse physicochemical and biological properties. Some benzodiazepine derivates well-known drugs with strong pharmacophoric moiety. An immense number pharmacological research on heterocycles derivatives have recently been conducted to explore its numerous potentials as better therapeutic candidates the treatment various disorders, benzodiazepines, however, one main sources interest many medicinal chemists. Researchers drawn nucleus synthesis new because potent moiety ring shape. Due emergence pathogenic strains' resistance presently available drugs, there has a constant demand more effective selective drugs. Benzodiazepine all desired qualities drug used useful agents. Given importance moiety, current review aims assess syntheses well properties potential molecular targets development.

Language: Английский

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Revolutionizing cancer treatment: nanotechnology-enabled photodynamic therapy and immunotherapy with advanced photosensitizers

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 4, 2023

Nanotechnology-enhanced photodynamic therapy (PDT) and immunotherapy are emerging as exciting cancer therapeutic methods with significant potential for improving patient outcomes. By combining these approaches, synergistic effects have been observed in preclinical studies, resulting enhanced immune responses to the capacity conquer immunosuppressive tumor microenvironment (TME). Despite challenges such addressing treatment limitations developing personalized strategies, integration of nanotechnology-enabled PDT immunotherapy, along advanced photosensitizers (PSs), represents an new avenue treatment. Continued research, development, collaboration among researchers, clinicians, regulatory agencies crucial further advancements successful implementation promising therapies, ultimately benefiting patients worldwide.

Language: Английский

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Anti-tumor immunity enhancement by photodynamic therapy with talaporfin sodium and anti-programmed death 1 antibody

Molecular Therapy — Oncolytics, Journal Year: 2023, Volume and Issue: 28, P. 118 - 131

Published: Jan. 2, 2023

Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer that employs photosensitizer with specific wavelength of light irradiation. PDT induces direct cell killing and enhancement effects on tumor immunity, but its underlying mechanism remains unknown. Here, we perform basic analysis the anti-tumor effect talaporfin sodium (TS)-PDT as well synergism immune checkpoint inhibitor anti-programmed death 1 (anti-PD-1) antibody. We estimate induced by TS-PDT induction damage-associated molecular patterns (DAMPs) in vitro. establish syngeneic mouse model bilateral flank tumors verify abscopal non-irradiated side. apoptosis, necrosis, autophagy-associated release and/or expression DAMPs Tumor growth was inhibited anti-PD-1 antibody combination group compared other single-treatment or non-treatment groups vivo. In summary, DAMPs, indicating it activates innate immunity. PD-1 blockage enhances immunity TS-PDT. Thus, our results demonstrate can potentially be used for therapy.

Language: Английский

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Genetically engineered nano‐melittin vesicles for multimodal synergetic cancer therapy

Bioengineering & Translational Medicine, Journal Year: 2023, Volume and Issue: 8(6)

Published: Jan. 4, 2023

Melittin, the principal constituent in bee venom, is an attractive candidate for cancer therapy. However, its clinical applications are limited by hemolysis, nonspecific cytotoxicity, and rapid metabolism. Herein, a novel genetically engineered vesicular antibody-melittin (VAM) drug delivery platform was proposed validated targeted combination VAM generated from cellular plasma membrane bio-synthetically fabricated, with recombinant protein (hGC33 scFv-melittin) being harbored displayed on cell membrane. The bioactive targetable nanomelittin conjugated hGC33 scFv could be released MMP14-responsive manner at tumor sites, which reduced off-target toxicity, especially hemolytic activity of melittin. Importantly, loaded small-molecule drugs or nanoparticles Nanomelittin formed pores membranes disturbed phospholipid bilayers, allowed anticancer agents (i.e., chemotherapeutic doxorubicin sonosensitizer purpurin 18 nanoparticles) co-delivered to penetrate deeper leading synergistic therapeutic effects. In particular, punching effect sonodynamic therapy further improved immunomodulatory activate immune response. Taken together, our findings indicate that clinically translatable VAM-based strategies represent universal, promising approach multimodal synergetic

Language: Английский

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Tumor Pigmentation Does Not Affect Light-Activated Belzupacap Sarotalocan Treatment but Influences Macrophage Polarization in a Murine Melanoma Model

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(1), P. 42 - 42

Published: Jan. 25, 2024

Purpose: Pigmentation in uveal melanoma is associated with increased malignancy and known as a barrier for photodynamic therapy. We investigated the role of pigmentation tumor behavior response to light-activated Belzupacap sarotalocan (Bel-sar) treatment pigmented (wild type) nonpigmented (tyrosinase knock-out [TYR knock-out]) cell line vitro murine model. Methods: The B16F10 (TYR knock-out) was developed using CRISPR/Cas9. After Bel-sar, cytotoxicity exposure damage-associated molecular patterns (DAMPs) were measured by flow cytometry. Treated cells co-cultured bone marrow-derived macrophages (BMDMs) dendritic (DCs) assess phagocytosis activation. Both lines injected subcutaneously syngeneic C57BL/6 mice. Results: Knock-out tyrosinase gene led loss immature melanosomes. Pigmented tumors contained more M1 fewer M2 compared amelanotic tumors. Bel-sar induced near complete death, accompanied enhanced DAMPs both lines, resulting BMDMs maturation DCs. shift delayed growth vivo models. Following treatment, especially their draining lymph nodes IFN-gamma positive CD8+T cells. Conclusions: influenced type infiltrating tumor, immunogenic death delay well models stimulated macrophage influx

Language: Английский

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Advantage of extracellular vesicles in hindering the CD47 signal for cancer immunotherapy

Journal of Controlled Release, Journal Year: 2022, Volume and Issue: 351, P. 727 - 738

Published: Oct. 7, 2022

The cluster of differentiation 47 (CD47) protein is abundantly expressed on various malignant cells and suppresses the phagocytic function macrophages dendritic cells. High CD47 expression levels are correlated with poor cancer survival. Antagonizing antibodies potent antitumor effects have been developed in clinical trials, but critical side effects, inducing anemia thrombocytopenia. To develop a safe blockade, we designed extracellular vesicles (EVs) harboring signal regulatory alpha (SIPRα)—EV-SIRPα (EVs that express SIPRα). EV-SIRPα showed minimal toxic hematologic parameters utilized RBCs as delivery vehicles to tumors rather than anemia. inhibited ligation residual molecules, which attribute EV-endocytosis-mediated depletion steric hindrance EV. In an immunologically cold tumor model, induced tumor-specific T-cell-mediated effects. When directly administered accessible lesions, monotherapy elicited abscopal effect B16F10 model by increasing immune cell infiltration CD8+-mediated immunity against non-treated tumors. combinational approach loading doxorubicin into dramatically reduced burden led 80% complete remission rate. Thus, EV-based blockade hematologically safe, has efficient signaling blocking efficacy, systemic recommended.

Language: Английский

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Ultrasound-enhanced nano catalyst with ferroptosis-apoptosis combined anticancer strategy for metastatic uveal melanoma

Biomaterials, Journal Year: 2023, Volume and Issue: 305, P. 122458 - 122458

Published: Dec. 30, 2023

Language: Английский

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