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The anti-PD-L1 immunotherapy has shown promise in treating cancer. However, certain patients with metastatic cancer have low response and high relapse rates. A main reason is systemic immunosuppression caused by exosomal PD-L1, which can circulate in the body and inhibit T cell functions. Here, we show that Golgi apparatus-Pd- l1 -/- exosome hybrid membrane coated nanoparticles (GENPs) can significantly reduce the secretion of PD-L1. The GENPs can accumulate in tumors through homotypic targeting and effectively deliver retinoic acid, inducing disorganization of the Golgi apparatus and a sequence of intracellular events including alteration of endoplasmic reticulum (ER)-to-Golgi trafficking and subsequent ER stress, which finally disrupts the PD-L1 production and the release of exosomes. Furthermore, GENPs could mimic exosomes to access draining lymph nodes. The membrane antigen of PD- l1 hydrogel, we have successfully realized a low recurrence rate and substantially extended survival periods in mice models with incomplete metastatic melanoma resection.-/- exosome on GENPs can activate T cells through a vaccine-like effect, strongly promoting systemic immune responses. By combining GENPs with anti-PD-L1 treatment in the sprayable in situ hydrogel, we have successfully realized a low recurrence rate and substantially extended survival periods in mice models with incomplete metastatic melanoma resection.

Background/aim: The rapid spread of COVID-19 resulted in the revision of the value of ultraviolet C (UVC) sterilization in working spaces. This study aimed at re-evaluating the anti-UVC activity of four groups of natural products against human melanoma COLO679 and human normal dermal fibroblast (HDFa) cells, based on chemotherapeutic index., Materials and Methods: Various cell lines were exposed to UVC for 3 min in the presence of increasing concentrations of test compounds and viable cell numbers were determined with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The anti-UVC activity was quantified by the ratio of the 50% cytotoxic concentration (determined without irradiation) to the 50% effective concentration (which abolished by 50% the UVC-induced loss of viability). Apoptosis was quantified as the subG1 population proportion following cell-cycle analysis., Results: Among four groups of major natural products, six phenylpropanoids showed the highest anti-UVC activity, followed by the lignified products and alkaline products that contain lignin and its degradation products. On the other hand, tannins and flavonoids showed lower activity due to their higher cytotoxicity. UVC-sensitive COLO679 cells lack dectin-1 protein expression., Conclusion: These data suggest the prominent anti-UVC activity of lignin degradation products, and the possible involvement of dectin-1 expression in UVC-sensitivity., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Currently, the combining photodynamic therapy (PDT) with photothermal therapy (PTT) modalities based on a single near infrared (NIR) laser irradiation and highly selective internalization still remain a challenge. Herein, a hierarchical dual-responsive cleavable nanosystem for synergetic NIR triggered PDT/PTT is reported. The engineered nanoplatform (Au NRs/Cur/UCNPs@PBE) is designed by loading curcumin (Cur, photosensitizer) on gold nanarods (Au NRs) to build PDT/PTT therapy system, which was encapsulated outside with upconversion nanoparticles (UCNPs) and then modified with phenylboronic double ester (PBE). The pH and ROS-responsive feature made Au NRs/Cur/UCNPs@PBE provide a fundamental structural evolution and improve the specificity and intracellular accumulation to tumors. Au NRs/Cur/UCNPs@PBE exhibited significant PDT and PTT efficiency against two type melanoma cells due to upconversion nanoparticles and Au NRs induced by an 808 nm laser. Notably, the platform can mainly activate apoptosis and partial ferroptosis to achieve the synergistic PDT/PTT, furthermore, the integrated PDT with PTT using Au NRs/Cur/UCNPs@PBE showcased a great antitumor efficacy in vivo superior to the other alone treatment. Our findings highlight that this intelligent nanoagents for synergistic phototherapy facilitate enhanced fighting melanoma and provide a promising strategy for melanoma theranostics., (Copyright © 2021. Published by Elsevier B.V.)