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Red‐Light‐Controlled Release of Drug–Ru Complex Conjugates from Metallopolymer Micelles for Phototherapy in Hypoxic Tumor Environments
Author(s) -
Sun Wen,
Wen Yan,
Thiramanas Raweewan,
Chen Mingjia,
Han Jianxiong,
Gong Ningqiang,
Wagner Manfred,
Jiang Shuai,
Meijer Michael S.,
Bonnet Sylvestre,
Butt HansJürgen,
Mailänder Volker,
Liang XingJie,
Wu Si
Publication year - 2018
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201804227
Subject(s) - micelle , biocompatibility , polymer , materials science , copolymer , conjugate , ethylene glycol , photodynamic therapy , drug delivery , biophysics , tumor microenvironment , combinatorial chemistry , chemistry , nanotechnology , cancer research , organic chemistry , tumor cells , medicine , biology , mathematical analysis , mathematics , aqueous solution , metallurgy , composite material
Traditional photodynamic phototherapy is not efficient for anticancer treatment because solid tumors have a hypoxic microenvironment. The development of photoactivated chemotherapy based on photoresponsive polymers that can be activated by light in the “therapeutic window” would enable new approaches for basic research and allow for anticancer phototherapy in hypoxic conditions. This work synthesizes a novel Ru‐containing block copolymer for photoactivated chemotherapy in hypoxic tumor environment. The polymer has a hydrophilic poly(ethylene glycol) block and a hydrophobic Ru‐containing block, which contains red‐light‐cleavable (650–680 nm) drug–Ru complex conjugates. The block copolymer self‐assembles into micelles, which can be efficiently taken up by cancer cells. Red light induces release of the drug–Ru complex conjugates from the micelles and this process is oxygen independent. The released conjugates inhibit tumor cell growth even in hypoxic tumor environment. Furthermore, the Ru‐containing polymer for photoactivated chemotherapy in a tumor‐bearing mouse model is applied. Photoactivated chemotherapy of the polymer micelles demonstrates efficient tumor growth inhibition. In addition, the polymer micelles do not cause any toxic side effects to mice during the treatment, demonstrating good biocompatibility of the system to the blood and healthy tissues. The novel red‐light‐responsive Ru‐containing polymer provides a new platform for phototherapy against hypoxic tumors.