pH-sensitive nanoliposomes for passive and CXCR-4-mediated marine yessotoxin delivery for cancer therapy.

Yessotoxin (YTX), a marine-derived drug, was encapsulated in PEGylated pH-sensitive nanoliposomes, covalently functionalized (strategy I) with SDF-1α and by nonspecific adsorption (strategy II), to actively target chemokine receptor CXCR-4. Cytotoxicity to normal human epithelial cells (HK-2) and prostate (PC-3) and breast (MCF-7) adenocarcinoma models, with different expression levels of CXCR-4, were tested. Strategy II exerted the highest cytotoxicity toward cancer cells while protecting normal epithelia. Acid pH-induced fusion of nanoliposomes seemed to serve as a primary route of entry into MCF-7 cells but PC-3 data support an endocytic pathway for their internalization. This work describes an innovative hallmark in the current marine drug clinical pipeline, as the developed nanoliposomes are promising candidates in the design of groundbreaking marine flora-derived anticancer nanoagents.