A Paclitaxel Prodrug Activatable by Irradiation in a Hypoxic Microenvironment
Shiyu Zhou, Xiuli Hu, Rui Xia, Shi Liu, Qing Pei, Guang Chen, Zhigang Xie, Xiabin Jing
Abstract
Abstract The innate hypoxic microenvironment of most solid tumors has a major influence on tumor growth, invasiveness, and distant metastasis. Here, a hypoxia‐activated self‐immolative prodrug of paclitaxel (PTX 2 ‐Azo) was synthesized and encapsulated by a peptide copolymer decorated with the photosensitizer chlorin e6 (Ce6) to prepare light‐boosted PTX nanoparticle (Ce6/PTX 2 ‐Azo NP). In this nanoparticle, PTX 2 ‐Azo prevents premature drug leakage and realizes specific release in hypoxic tumor microenvironment and the photosensitizer Ce6 not only efficiently generates singlet oxygen under light irradiation but also acts as a positive amplifier to promote the release of PTX. The combination of photodynamic therapy (PDT) and chemotherapy results in excellent antitumor efficacy, demonstrating the great potential for synergistic cancer therapy.