CD44-Targeted Photoactivatable Polymeric Nanosystem with On-Demand Drug Release As a "photoactivatable Bomb" for Combined Photodynamic Therapy-Chemotherapy of Cancer.
ACS applied materials & interfaces(2023)
摘要
Nowadays, the combined use of chemotherapy and photodynamic therapy (PDT) remains the most popular strategy for cancer treatment with high theraprutic efficacy. However, targeted therapy with the on-demand release of drugs is what most clinical treatments lack, leading to heavy side effects. Herein, a new CD44-targeted and red-light-activatable nanosystem, Ru-HA@DOX nanoparticles (NPs), was developed by conjugating hydrophilic biodegradable hyaluronic acid (HA) and hydrophobic photoresponsive ruthenium (Ru) complexes, which could encapsulate the chemotherapeutic drug doxrubicin (DOX). Ru-HA@DOX NPs can selectively accumulate at the tumor through the enhanced permeability and retention (EPR) effect and CD44-mediated endocytosis, thus avoiding off-target toxicity during circulation. After 660 nm of irradiation at the tumor site, Ru-HA@DOX NPs, as a "photoactivatable bomb", was split via the photocleavable Ru-N coordination bond to fast release DOX and produce singlet oxygen (1O2) for PDT. In general, Ru-HA@DOX NPs retained its integrity before irradiation and possessed minimal cytotoxicity, while under red-light irradiation, Ru-HA@DOX NPs showed significant cytotoxicity due to the release of DOX and production of 1O2 at the tumor. Chemotherapy-PDT of Ru-HA@DOX NPs resulted in a significant inhibition of tumor growth in A549-tumor-bearing mice and reduced the cardiotoxicity of DOX. Therefore, this study offers a novel CD44-targeted drug-delivery system with on-demand drug release for synergistic chemotherapy-PDT.
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关键词
photoactivatable nanosystem,ruthenium polymetallodrug,on-demand drug release,chemotherapy-photodynamictherapy,CD44-targeted
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