Delivery of gefitinib loaded nanoparticles for effectively inhibiting prostate cancer progression

Abstract

Androgen deprivation therapy is administered to suppress the growth of prostate cancer (PCa). However, some cells continue to proliferate independent of hormones, leading to the development of castration-resistant prostate cancer (CRPC). Overexpression of the epidermal growth factor receptor (EGFR) has been observed in CRPC and is associated with an unfavorable prognosis. Gefitinib (GEF) is an EGFR inhibitor used to treat patients with CRPC. Nevertheless, some clinical studies have reported that gefitinib does not result in prostate-specific antigen (PSA) or objectively measurable CRPC reactions. This lack of response may be attributed to the limited solubility in water, high side effects, low tumor aggregation, and insufficient tumor-specific reactions of GEF. In order to tackle these obstacles, we present a practical and efficient approach to administer GEF, encompassing the utilization of biocompatible nanostructures as a vehicle for drug delivery to augment its bioaccessibility and curative potency. Despite their small particle size, poly(D,L-lactide-co-glycolide) acid nanoparticles (PLGA NPs) exhibit a high drug-loading capacity, low toxicity, biocompatibility, biodegradability, and minimal immunogenicity. The drug delivery efficiency can be improved by employing GEF@PLGA NPs, which could also enhance drug cytotoxicity and impede the advancement of prostate cancer. Moreover, through experiments in vivo, it has been verified that GEF@PLGA NPs exhibit selective accumulation in the tumor and effectively restrain tumor growth. Therefore, the GEF@PLGA NPs hold great promise for the treatment of PCa.