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Tumor‐Microenvironment‐Activated In Situ Self‐Assembly of Sequentially Responsive Biopolymer for Targeted Photodynamic Therapy
Author(s) -
Wang Xuan,
Li Menghuan,
Hou Yanhua,
Li Yanan,
Yao Xuemei,
Xue Chencheng,
Fei Yang,
Xiang Yang,
Cai Kaiyong,
Zhao Yanli,
Luo Zhong
Publication year - 2020
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.202000229
Subject(s) - photosensitizer , biopolymer , materials science , biophysics , linker , polyethylene glycol , tumor microenvironment , hyaluronic acid , endocytosis , photodynamic therapy , peg ratio , conjugated system , chemistry , biochemistry , polymer , organic chemistry , tumor cells , cancer research , cell , biology , genetics , finance , computer science , economics , composite material , operating system
A sequentially responsive photosensitizer‐integrated biopolymer is developed for tumor‐specific photodynamic therapy, which is capable of forming long‐retained aggregates in situ inside tumor tissues. Specifically, the photosensitizer zinc phthalocyanine (ZnPc) is conjugated with polyethylene glycol (PEG) via pH‐labile maleic acid amide linker and then immobilized onto the hyaluronic acid (HA) chain using a redox‐cleavable disulfide linker. The PEG segment can enhance blood circulation of the molecular carrier after intravenous administration and be shed after reaching the acidic tumor microenvironment, allowing the remaining fragment to self‐assemble into large clusters in situ to avoid backward diffusion and improve tumor retention. This process is driven by hydrophobic interactions and does not require additional external actuation. The aggregates are then internalized by the tumor cells via HA‐facilitated endocytosis, and the high glutathione level in tumor cells eventually leads to the intracellular release of ZnPc to facilitate its interaction with the subcellular lipid structures. This tumor‐triggered morphology‐based delivery platform is constructed with clinically tested components and could potentially be applied to other hydrophobic therapeutics.