Co-Delivery of Docetaxel and p44/42 MAPK siRNA Using PSMA Antibody-Conjugated BSA-PEI Layer-by-Layer Nanoparticles for Prostate Cancer Target Therapy.

Abstract

How to overcome the low accumulation of chemotherapeutic agent in tumor tissue and exhibit multitherapeutics remains an ongoing challenge for cancer treatment. Here, a simple method is demonstrated that used to prepare prostate-specific membrane antigen antibody (PSMAab )-conjugated fluorescent bovine serum albumin (BSA)-branched polyethylenimine layer-by-layer nanoparticles (BSA-PEILBL NPs) for co-delivery of docetaxel (DTX) and p44/42 mitogen-activated protein kinase (MAPK) small interfering RNA (p44/42 MAPK siRNA) as synergistic and selective inhibition of cancer cell proliferation platform. The results show the levels of α-tubulin and p44/42 MAPK in CWR22R cells are significantly reduced after treatment with PSMAab -conjugated DTX/BSA-PEILBL /siRNA NPs. Consequently, the 50% cellular growth inhibition (IC50 ) values of the NPs loaded with both DTX and p44/42 MAPK siRNA are ≈2.1-fold less than those for the NPs only loaded with DTX. The median survival significantly prolongs from 18 d to upward 45 d compared to mice that receive same dose (12 mg kg-1 ) of free DTX. The results suggest this synergistic delivery system may be a promising clinical treatment in prostate cancer.