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Cyclo(RGD)‐Decorated Reduction‐Responsive Nanogels Mediate Targeted Chemotherapy of Integrin Overexpressing Human Glioblastoma In Vivo
Author(s) -
Chen Wei,
Zou Yan,
Zhong Zhiyuan,
Haag Rainer
Publication year - 2017
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201601997
Subject(s) - in vivo , biodistribution , doxorubicin , confocal microscopy , integrin , u87 , in vitro , cancer research , chemistry , nanogel , mtt assay , biophysics , microbiology and biotechnology , pharmacology , biochemistry , cell , chemotherapy , drug delivery , biology , genetics , organic chemistry
Cyclo(Arg‐Gly‐Asp) peptide (cRGD) decorated disulfide (SS) containing poly(vinyl alcohol) nanogels (cRGD‐SS‐NGs) with an average diameter of 142 nm prepared by inverse nanoprecipitation, “click” reaction, and cRGD conjugation are developed for targeted treatment of integrin overexpressing human glioblastoma in vivo. Doxorubicin (DOX) release from cRGD‐SS‐NGs is highly inhibited under physiological conditions, while accelerated at endosomal pH and in response to cytoplasmic concentration of glutathione. Confocal microscopy shows that cRGD‐SS‐NGs facilitate the cellular uptake and intracellular DOX release in α v β 3 integrin overexpressing human glioblastoma U87‐MG cells. DOX‐loaded cRGD‐SS‐NGs present much better killing activity toward U87‐MG cells than that for nontargeted nanogels determined by MTT assay. The in vivo imaging and biodistribution studies reveal that DOX‐loaded cRGD‐SS‐NGs have a much better tumor targetability toward human U87‐MG glioblastoma xenograft in nude mice. Also the tumor growth is effectively inhibited by treatment with DOX‐loaded cRGD‐SS‐NGs, while continuous tumor growth is observed for mice treated with nondecorated nanogels as well as free DOX. Furthermore, the treatment with DOX‐loaded cRGD‐SS‐NGs has much fewer side effects, rendering these nanogels as a new platform for cancer chemotherapy in vivo.