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Imaging‐Guided pHe and Glutathione Dual Responsive Polypeptide Nanogel for Smart Drug Delivery
Author(s) -
Jing Titao,
Li Tuanwei,
Ruan Zheng,
Cheng Quan,
Yan Lifeng
Publication year - 2018
Publication title -
macromolecular materials and engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.913
H-Index - 96
eISSN - 1439-2054
pISSN - 1438-7492
DOI - 10.1002/mame.201800060
Subject(s) - nanogel , drug delivery , confocal microscopy , materials science , glutathione , biophysics , conjugated system , intracellular , cyanine , chemistry , fluorescence , nanotechnology , biochemistry , microbiology and biotechnology , biology , polymer , physics , composite material , quantum mechanics , enzyme
A negatively charged polypeptide nanogel, near‐infrared (NIR) cyanine dye (Cy5.5) conjugated and 2,3‐dimethylmaleic anhydride (DMA) modified poly‐ l ‐lysine‐co‐ l ‐cystine (CDPLC), is synthesized and is used as an imaging‐guided sequential drug delivery system. The CDPLC nanogel can respond to two general stimulations in sequence: extracellular tumor acidic microenvironment pHe (6.8–6.5) and intracellular high concentration glutathione (GSH). Under pHe, the DMA shell of the nanogel is removed and a charge reversal takes place, resulting in positively charged nanogel which can be internalized by cancer cells easily. Once internalized into tumor cells, the increased intracellular GSH concentration further promotes DOX release from the nanogel and DOX is enriched to the nucleus. Cy5.5 is conjugated to the nanogel as an NIR fluorescent probe, making it possible for imaging‐guided drug delivery, which is confirmed by the MTT and confocal laser scanning microscopy via in vitro experiments. The as‐prepared nanogel is a potential theranostic for cancer therapy.