Abstract
A novel kind of anti-cancer pharmacosome (named NPC-D) derived from Doxifluridine (5′-DFUR) was described, which could be activated by tumor microenvironments (TMEs). The NPC-D with H2O2-sensitive linker was dispersed well in water and simultaneously interacted with nucleic acids including plasmids encoding miR-122 (p122) and EpCAM-targeted aptamer (ap1) via charge interaction and hydrogen bonding. The integrated nanosystem (p122-ap1@NPC-D) was found to unleash by programmed TMEs (high level of H2O2 and low pH) to efficiently transfect miR-122 into MHCC-LM3 cells, followed by the releases of 5-FU. Besides, p122-ap1@NPC-D significantly countered the chemotherapy resistance and played a synergistic effect. These unique nanoparticles dramatically enhanced the anti-proliferation, and modulated the cellular apoptosis by the down-regulation of various signal pathways which imparted a bright application prospect in HCC treatment.
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