Institute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine , Baltimore, Maryland 21201, United States.
Department of Oncology, BenQ Medical Center, Nanjing Medical University , Nanjing 210029, China.
ACS Nano. 2018 Feb 27;12(2):2017-2026. doi: 10.1021/acsnano.8b00081. Epub 2018 Feb 2.
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 ∼90 nm in diameter that are self-assembled from lanthanide-doped nanoparticles (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.
开发一种复杂的纳米医学平台，将治疗药物有效地、安全地递送到肿瘤/癌细胞中，这在纳米医学领域仍然是一个挑战。特别是，能够克服生物屏障的可靠肽药物传递系统仍然缺乏。在这里，我们开发了一种简单、快速、稳健的策略，制造出由掺杂镧系元素的纳米颗粒（5nm）自组装而成的直径约为 90nm 的纳米团簇，该纳米团簇由两种针对不同靶点的抗癌肽（BIM 和 PMI）和一种针对癌细胞的环状肽 iNGR 组成。肽-镧系元素纳米团簇（LDC-PMI-BIM-iNGR）增强了肽药物对蛋白水解的抗性，在肿瘤微环境中存在的还原条件下解体，并抑制体外和体内的癌细胞生长。值得注意的是，LDC-PMI-BIM-iNGR 在体内表现出极低的全身毒性和副作用。因此，肽-镧系元素纳米团簇可用作癌症治疗中安全、靶向和高效肽药物传递的理想多功能平台。
