PD-L1 Monoclonal Antibody-Conjugated PEGylated Nanoparticles forBrain Cancer Immuno-Chemotherapy via Activation of STING Pathway

Abstract Immunotherapy for cancer is regarded as an alternative to conventional chemotherapy. Novel approach to cancer treatment called STING-targeted activation is being studied in great detail. Thus, self-assembly PEGylated coated, ovalbumin (OVA), loaded PC7A polymer, conjugated with PD-L1 (programmed death-ligand-1) monoclonal antibody (mAb) [OVA-PEG-PC7-A-mAb] was prepared by emulsion solvent evaporation. Further, physicochemical characterization and release kinetic was performed. Further, PD-L1-mAb-conjugated NPs, investigated for cellular-uptake, cytotoxic-effects, and apoptosis in PD-L1-expressing human GC cell lines, and in vivo pharmacokinetic and bio-distribution study was performed. The investigation of structure and interaction activity of PD-L1-OVA-PEG-PC7-A-mAb NPs involved the utilization of X-ray photoelectron spectroscopy, which confirmed the presence of PD-L1-mAbs on the surface of NPs. Cellular-uptake examination demonstrated that NPs conjugated with antibodies exhibited expressively enhanced levels of cellular-uptake. NPs demonstrated by in-vitro cytotoxicity experiment on 6-glioma cell lines proof the targeting efficiency. Ova-PEG-PC7-A-mAb, NPs showed greatest STING pathway activation, confirmed by higher release of IFN-𝛽) and IL-6. In-vivo study biodistribution and pharmacokinetic confirm the specific targeting in brain region. Our findings, presented here, demonstrate that biological immune-therapeutic potential of OVA-PEG-PC7-A-mAb NPs by activation mechanism of the STING pathway using PD-L1 mAbs in brain cancer therapy.