期刊
ACS NANO
卷 12, 期 2, 页码 2017-2026出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b00081
关键词
multifunctional nanocluster; stimuli-responsive; peptides; targeted delivery; p53 activator; safe cancer therapy
类别
资金
- Natural Science Basic Research Plan in Shaanxi Province of China [2015JQ5165]
- State Key Laboratory for Mechanical Behavior of Materials [20161801]
- National Natural Science Foundation of China [51502237]
Developing a sophisticated nanomedicine platform to deliver therapeutics effectively and safely into tumor/cancer cells remains challenging in the field of nanomedicine. In particular, reliable peptide drug delivery systems capable of overcoming biological barriers are still lacking. Here, we developed a simple, rapid, and robust strategy to manufacture nanoclusters of similar to 90 nm in diameter that are self-assembled from lanthanide-doped nano particles (5 nm), two anticancer peptides with different targets (BIM and PMI), and one cyclic peptide iNGR targeted to cancer cells. The peptide-lanthanide nanoclusters (LDC-PMI-BIM-iNGR) enhanced the resistance of peptide drugs to proteolysis, disassembled in response to reductive conditions that are present in the tumor microenvironment and inhibited cancer cell growth in vitro and in vivo. Notably, LDC-PMI-BIM-iNGR exhibited extremely low systemic toxicity and side effects in vivo. Thus, the peptide-lanthanide nanocluster may serve as an ideal multifunctional platform for safe, targeted, and efficient peptide drug delivery in cancer therapy.
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