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A Hypoxia‐Responsive Albumin‐Based Nanosystem for Deep Tumor Penetration and Excellent Therapeutic Efficacy
Author(s) -
Yang Guangbao,
Phua Soo Zeng Fiona,
Lim Wei Qi,
Zhang Rui,
Feng Liangzhu,
Liu Guofeng,
Wu Hongwei,
Bindra Anivind Kaur,
Jana Deblin,
Liu Zhuang,
Zhao Yanli
Publication year - 2019
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201901513
Subject(s) - singlet oxygen , photosensitizer , tumor hypoxia , photodynamic therapy , materials science , conjugated system , biophysics , in vivo , nanoparticle , human serum albumin , hypoxia (environmental) , penetration (warfare) , bovine serum albumin , cancer research , oxygen , nanotechnology , chemistry , photochemistry , radiation therapy , biochemistry , medicine , organic chemistry , biology , surgery , polymer , microbiology and biotechnology , operations research , engineering , composite material
Uncontrolled cancer cell proliferation, insufficient blood flow, and inadequate endogenous oxygen lead to hypoxia in tumor tissues. Herein, a unique type of hypoxia‐responsive human serum albumin (HSA)‐based nanosystem (HCHOA) is reported, prepared by cross‐linking the hypoxia‐sensitive azobenzene group between photosensitizer chlorin e6 (Ce6)‐conjugated HSA (HC) and oxaliplatin prodrug‐conjugated HSA (HO). The HCHOA nanosystem is stable under normal oxygen partial pressure with a size of 100–150 nm. When exposed to the hypoxic tumor microenvironment, the nanosystem can quickly dissociate into ultrasmall HC and HO therapeutic nanoparticles with a diameter smaller than 10 nm, significantly enabling their enhanced intratumoral penetration. After the dissociation, the quenched fluorescence of Ce6 in the produced HC nanoparticles can be recovered for bioimaging. At the same time, the production of singlet oxygen is increased because of the enhancement in the photoactivity of the photosensitizer. On account of these improvements, combined photodynamic therapy and chemotherapy is realized to display superior antitumor efficacy in vivo. Based on this simple strategy, it is possible to achieve the dissociation of hypoxic‐responsive nanosystem to enhance the tumor penetration and therapeutic effect.