Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 12, Pages 11865-11875Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b21580
Keywords
dual-responsive; self-adaptively transform; hierarchical disassemble; tumor penetration; chemotherapy; systematic evaluation
Funding
- National Natural Science Foundation of China [81202483, 81773668, 81874305, 81302721]
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It is generally known that, for nanoparticles in cancer therapy, sufficient tumor penetration needs a minor particle size, while long in vivo circulation time needs a larger particle size. It is hard to balance them because they are standing on either side of a seesaw. To address these two different requirements, a dual-responsive size-shrinking nanocluster can self-adaptively respond to a complicated tumor microenvironment and transform its particulate property to overcome sequential in vivo barriers and reach a preferable antitumor activity. The nanocluster (RPSPT@SNCs) could preferentially accumulate into tumor tissue and dissociate under extracellular matrix metalloproteinase-2 (MMP-2) to release small-sized micelle formulations (RPSPTs). RPSPT possesses favorable tumor penetration and tumor targeting capability to deliver the antitumor agent paclitaxel (PTX) into deep regions of solid tumor. The intracellular redox microenvironment can also accelerate drug accumulation. The prepared RPSPT@SNCs possesses enhanced cell cytotoxicity and tumor penetration capability on MCF-7 cells and a favorable antitumor activity on the xenograft tumor mouse model.
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