LHRH-peptide conjugated dextran nanoparticles for targeted delivery of cisplatin to breast cancer

Abstract

Cisplatin is one of the most common anticancer agents for treating different kinds of solid tumors today. However, its broader therapeutic applications are limited by the severe side effects and nonspecific biodistribution. In this study, luteinizing hormone-releasing hormone (LHRH)-targeted polysaccharide nanoparticles for tumor-targeted delivery and controlled release of cisplatin were developed. This nanoparticle delivery system possessed the following unique properties: (1) as the degradation products of the carrier, both dextran and succinic acid have been proved by the United States Food and Drug Administration for parenteral use, indicating good safety and great application potential; (2) both the drug loading and LHRH conjugation procedures were carried out with efficiency in aqueous medium without the use of organic solvents, thus representing a green chemistry approach; and (3) the design followed the principle of drug encapsulation first and subsequent targeting ligand modification, guaranteeing that the targeting molecules were conjugated on the surface of nanoparticles. As compared to free cisplatin, both the non-targeted and targeted nanoparticles displayed sustained drug release, prolonged blood circulation and reduced systemic toxicity. Foremost, the LHRH-targeted nanoparticles led to significant higher cellular internalization in MCF-7 tumor cells in vitro and enhanced accumulation in MCF-7 xenograft tumors in vivo, compared with the non-targeted counterparts. Systemic delivery of the targeted nanoparticles carrying cisplatin via intravenous injection showed enhanced tumor suppression in MCF-7 tumor bearing mice compared to the non-targeted nanoparticles and free CDDP. Collectively, the LHRH-mediated polysaccharide nanoparticles appeared to be a promising nanomedicine drug delivery system for tumor-targeted delivery of cisplatin.