PLGA nanoparticles delivering CPT-11 combined with focused ultrasound inhibit platinum resistant ovarian cancer

BACKGROUND: Ovarian cancer cells show resistance to platinum drugs treatment, which brings a big challenge to clinical therapeutics. This study aimed to construct effective drug delivering nanoparticles specifically targeting ovarian cancer cell. METHODS: Poly lactic-co-glycolic acid (PLGA) were used to form Nano-spheres by double emulsion method, and to deliver CPT-11. Connected with targeted LHRH-a molecules, their effects were tested by ovarian cancer cell A2780/DDP in vitro and in vivo. RESULTS: We successfully constructed PLGA nanoparticles carrying LHRH-a (Luteinizing hormone releasing hormone analogue) and CPT-11 (irinotecan HCl trihydrate), which can specifically target LHRH receptor high expression ovarian cancer cell A2780/DDP (cisplatin). Combined with focused ultrasound in vitro, LHRH-a/CPT-11/PLGA nanoparticles significantly inhibited the proliferation of A2780/DDP cells (a cisplatin-resistant A2780 cell line), and the cells were obviously arrested at S phase. Both the mRNA expression and protein level of Caspase3 increased, while Bcl-2 and MMP2 declined, which promoted apoptosis. In vivo, LHRH-a/CPT-11/PLGA nanoparticles bind specifically with LHRH receptor on xenograft tumors of A2780/DDP. With focused ultrasound, LHRH-a/CPT-11/PLGA nanoparticles inhibited the growth of A2780/DDP xenograft tumors significantly. The expression level of VEGF, Bcl-2 and MMP2 reduced, while Caspase3 increased in tumors. CONCLUSIONS: CPT-11 delivering PLGA nanoparticles with LHRH-a specifically target ovarian cancer cell A2780/DDP, and work locally when combined with focused ultrasound. They increase local drug concentration and reduce side effects. This research may provide a new effective therapeutic strategy for recurrent platinum resistant ovarian cancer.