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Synthesis of a Block Copolymer Exhibiting Cell-Responsive Phytochemical Release for Cancer Therapy.
ACS Applied Materials & Interfaces 2018 July 6
Phytochemicals constitute a promising class of therapeutics for the treatment of various diseases, but their delivery poses significant challenges. In this work, a nanoscale polyactive emulsion was designed for smart, cell-responsive delivery of a curcumin prodrug (curcumin dicarboxylate, CDA) that was chemically conjugated to enzymatically labile oligo-peptides with polycaprolactone (PCL) as the carrier. Matrix metalloproteinase (MMP)-sensitive (PLGLYAL) or nonsensitive (GPYYPLG) peptides were used as spacers for conjugating CDA and PCL. This CDA nanoemulsion incorporating the MMP-sensitive sequence exhibited markedly higher anti-cancer activity, cell internalization, and generation of reactive oxygen species in cancer cells in vitro than the control with the nonsensitive oligopeptide. Moreover, the nanopolyactives induced minimal cytotoxicity in noncancerous cell line. This work presents a unique strategy to engineer smart nano-polyactives for efficient and targeted delivery of phytochemicals.
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