Prodrug and Glucose Oxidase Coloaded Photodynamic Hydrogels for Combinational Therapy of Melanoma

Abstract

With the advantages of high safety and selectivity, photodynamic therapy (PDT) has been widely used for cancer treatments, while the anticancer efficacy is often limited because of its relying on oxygen concentrations. Therefore, sole PDT fails to achieve the desired therapeutic effect for hypoxic tumors. To address this issue, we herein report the construction of prodrug and glucose oxidase (GOx) coloaded alginate (ALG) hydrogels for PDT-combined chemotherapy of melanoma. The hydrogels are in situ formed in tumor sites after injection of ALG solution containing semiconducting polymer nanoparticles, hypoxia-responsive prodrug tirapazamine (TPZ), and GOx, which is based on chelation of ALG by endogenous Ca 2+ . Due to the presence of semiconducting polymer nanoparticles acting as photosensitizers, the hydrogels mediate PDT to produce singlet oxygen ( 1 O 2 ) for directly killing tumor cells, in which oxygen is consumed to create a more hypoxic tumor microenvironment. Moreover, the loaded GOx within hydrogels can deplete oxygen to further aggravate tumor hypoxia. As such, TPZ is effectively activated by hypoxia to cause cancer cell death via chemotherapy. Thus, the hydrogels with laser irradiation achieve a combinational action of PDT with chemotherapy to almost completely eradicate tumors, leading to a much higher therapeutic efficacy relative to sole PDT. This study will provide a promising injectable hydrogel platform for effective treatments of cancer.

Nongenetic Optical Modulation of Pluripotent Stem Cells Derived Cardiomyocytes Function in the Red Spectral Range

“…[28] Due to its distinct optoelectronic properties, it has been widely employed for the realization of organic photovoltaic cells, [29][30][31] but, to the best of our knowledge, it was only rarely considered for bioelectronics applications. [14,16,[32][33][34][35][36] Figure S1A (Supporting Information) shows the PCPDTBT optical absorption spectrum and its chemical structure.…”

The fusion of light and immunity: Advancements in photoimmunotherapy for melanoma

“…Utilize PDT-mediated hypoxia to activate the prodrug for antimelanoma benefit [89] Various micelle or liposome delivery mechanisms Enhanced specificity and uptake of photosensitizing agents to melanoma cells, enhanced photosensitizer stability, easy codelivery of chemotherapies or other agents, enhanced ROS production and cell death [90][91][92][93][94][95][96][97][98][99][100] Monoclonal antibody conjugation or particle-coating Improved specificity to melanoma cells and flexibility with targeting options [57,95,101,102] Depigmentation agents, photobleaching, using light wavelengths out of the melanin absorbance range Enhanced PDT sensitivity and ROS production in melanotic melanoma [35,[103][104][105] further strengthening anti-tumor immunity. NIR PIT is a recently developed method of antibody-conjugated PDT, specifically designed around ICD induction.…”

Superior Drug Delivery Performance of Multifunctional Bilosomes: Innovative Strategy to Kill Skin Cancer Cells for Nanomedicine Application

“… 7 Unlike conventional therapeutic options, PDT limits damage to healthy cells and has high selectivity and minimal systemic side effects. 8 , 9 The action of PDT is based on a phototoxic reaction by combining photosensitizing agents and laser radiation at a specific wavelength to generate reactive oxygen species (ROS) that are fatal to cancer cells. It can induce tumor cell necrosis, tumor blood vessel damage, and immunogenic tumor cell death, activating the immune response against cancer and thus indicating significant prospects for clinical application.…”