Reduction-sensitive polymeric nanocarrier with near-infrared
fluorescence
probe has been prepared. Disulfide-cross-linked polypeptide nanogel
with near-infrared fluorescence property (NIRF nanogel) was first
synthesized, then the anticancer drug doxorubicin was encapsulated
into polypeptide core of the NIRF nanogel to prepare a drug carrier
with near-infrared fluorescence (NIRF prodrug). In vitro drug release
study of the NIRF prodrug revealed an accelerated release behavior
in the presence of 10 mM glutathione (GSH). Cellular uptake studies
of both the NIRF nanogel and NIRF prodrug showed that they could enter
cell via endocytosis. With the aid of NIRF labeling, direct imaging
of the drug release from NIRF nanogel was accomplished, and drug molecules
released subsequently migrated into nucleus while the NIRF nanogel
still remained in cytoplasm. In vivo distribution of the NIRF nanogel
and NIRF prodrug on tumor-bearing nude mice shows that both of them
accumulated at tumor place at 24 h after tail veil injection via enhanced
permeability and retention (EPR) effect. The NIRF prodrug prepared
here has the potential application for the theranosis of cancer.
A novel disulfide core cross-linked PEGylated polypeptide nanogel has been synthesized by a one-step ring opening copolymerization of γ-benzyl L-glutamate N-carboxyanhydride and L-cystine N-carboxyanhydride using an amino group-terminated poly(ethylene glycol) methyl ether as initiator. Characterization of products confirms the formation of a core cross-linked PEGylated nanogel with disulfide linkages with a size of about 250 nm, and these studies also confirm that this nanogel can easily be broken by glutathione. Cell viability experiments show the good biocompatibility of the as-prepared polymer. Studies relating to loading and controlled release of indomethacin under reduction-sensitive conditions reveal that the nanogel is a good candidate for drug delivery systems.
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