Tumor-Targeting Polycaprolactone Nanoparticles with Codelivery of Paclitaxel and IR780 for Combinational Therapy of Drug-Resistant Ovarian Cancer.

Synergetic treatments that combine chemotherapy with photothermal/photodynamic therapy have been developed as promising new strategies for cancer therapy, especially for drug-resistant cancers. To achieve optimized synergetic outcomes for cancer therapy, it is highly desirable to selectively and simultaneously deliver both chemotherapeutics and near-infrared photosensitizers to the cancer tissues and cells, enhancing local accumulation. Here we report the preparation of poly-ε-caprolactone nanoparticles (PCL NPs) using bovine albumin as a stabilizer; the nanoparticles are loaded with IR780 and paclitaxel (PTX) for combinational phototherapy and chemotherapy. Moreover, in order to enable active targeting toward ovarian cancer, a specific peptide recognizing luteinizing hormone-releasing hormone receptors (LHRH) on ovarian cancer cells was covalently grafted onto the surface of the as-prepared NPs. As a result, LHRH peptide modified PCL (PCL-LHRH) NPs demonstrated increased internalization in ovarian tumor cells in vitro and selective targeting in tumor xenografts in vivo. PTX and IR780 can be efficiently encapsulated into PCL-LHRH NPs by an oil-in-water emulsion and solvent evaporation method. The systematic administration of ovarian tumor targeting PCL-LHRH/IR780-PTX can efficiently hinder the growth of drug-resistant xenografts in vivo with the assistance of an 808 nm near-infrared laser. These findings indicate that peptide mediated tumor targeting multifunctional nanomaterials may have remarkable profits in controlled drug delivery and synergistic therapy on drug-resistant cancer.