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

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 (PSMA_ab)-conjugated fluorescent bovine serum albumin (BSA)-branched polyethylenimine layer-by-layer nanoparticles (BSA-PEI_LBL 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 PSMA_ab-conjugated DTX/BSA-PEI_LBL/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. (Figure presented.).