Exosomes Derived from Nanocomplex-Loaded Macrophages for Targeted Delivery of Docetaxel and siPLK1 against Castrate-Resistance Prostate Cancer

Abstract

Background. As a class of naturally occurring nanoparticles with low immunogenicity and high biocompatibility, exosomes have become a promising drug carrier for cancer therapy. However, their clinical applications remain a challenge due to their unsuitable donors, low scalability, as well as insufficient targeting ability. Here, we describe and validate a new strategy for drug loading into exosomes. We developed a folate-conjugated exosome (Co-Exo-FA) derived from nanocomplex-loaded Raw264.7 macrophages. This Co-Exo-FA containing docetaxel (DTX) and PLK1 siRNA (siPLK1) could be used for targeted therapy of castrate-resistance prostate cancer (CRPC).Results. Our results showed that Co-Exo-FA exhibited high stability, enhanced cancer targeting ability, and led to the suppression of tumor growth with reduced toxicity in vivo. Moreover, the delivery of siPLK1 and DTX using an exosome system effectively silenced the PLK1 gene and exhibited improved anticancer effects.Conclusion. Our results indicated that we managed to overcome major barriers to the efficient utility of exosomes and demonstrated the synergistic efficacy of siPLK1 and DTX in the treatment of CRPC, highlighting their potential value in therapeutic clinical applications.