Self-Assembled Peptide-Lanthanide Nanoclusters for Safe Tumor Therapy: Overcoming and Utilizing Biological Barriers to Peptide Drug Delivery.

Developing sophisticated nanomedicine platform to deliver therapeutics effectively and safely into tumor/cancer cells remains challenging in nanomedicine field. 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 (5nm), two anti-cancer peptides with different targets (Bim and PMI) and one cyclicpeptide 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 effect 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.