Multifunctional Polymeric Nanoparticles Codelivering Paclitaxel and Monoclonal Antibodies for Triple Combination Therapy of Colorectal Cancer.

Combination therapy is a promising strategy for clinically nonresectable colorectal cancer (CRC) treatment, but its efficacy is compromised by challenges such as cumbersome dosing regimens, poor targeting, high toxicity, and rapid drug clearance. To address these limitations, we designed a functional multitargeted polymeric nanoparticle system (PTX+ATE+BEV-TNPs) modified with octreotide (OCT) and chondroitin sulfate (CS) as targeting ligands to simultaneously encapsulate the chemotherapeutic drug paclitaxel (PTX), the anti-PD-L1 antibody atezolizumab (ATE), and the anti-VEGF antibody bevacizumab (BEV) for triple combination therapy of CRC. The optimized nanoparticles exhibited high endocytosis efficiency and effective lysosome escape, significantly inhibiting the proliferation of tumor cells and promoting their apoptosis. Following systemic administration, PTX+ATE+BEV-TNPs could effectively achieve tumor-targeted codelivery of small-molecule drugs and macromolecular antibodies, promising therapeutic outcomes and displaying good biocompatibility in a CRC mouse model. Overall, PTX+ATE+BEV-TNPs present a viable strategy for CRC and other cancer treatments, demonstrating potential for future translational applications.