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A Paclitaxel Prodrug Activatable by Irradiation in a Hypoxic Microenvironment
Author(s) -
Zhou Shiyu,
Hu Xiuli,
Xia Rui,
Liu Shi,
Pei Qing,
Chen Guang,
Xie Zhigang,
Jing Xiabin
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202008732
Subject(s) - photodynamic therapy , prodrug , photosensitizer , paclitaxel , singlet oxygen , cancer research , tumor microenvironment , tumor hypoxia , chemistry , hypoxia (environmental) , chemotherapy , biophysics , pharmacology , medicine , radiation therapy , biochemistry , oxygen , photochemistry , tumor cells , biology , organic chemistry
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.