Fabrication of Co-delivery of Bortezomib and Vincristine Loaded Chitosan Cross-linked Polymeric Nanoparticles: Evaluation of Anticancer Activity and Apoptosis Induction in Lung Cancer Cells

Targeting crucial pathways in cancer cells with combination drugs becomes vital as treatment resistance is reduced and the drug's efficacy improves even at low doses. Bortezomib (BTZ) and vincristine (VCR) are chemotherapy drugs provided to individuals with solid tumors. This work suggests encapsulating BTZ and VCR in chitosan (CS) nanoparticles (CSNPs@BTZ-VCR) grafted polymers to combat cancer. To enhance the solubility of CSNPs further cross-linked with polyethylene glycol (PEG) (PEG/CSNPs@BTZ-VCR). Several methods were used to examine the NPs. SEM images showed nanoparticle fabrication, drug loading into CSNPs, and PEG cross-linking. The studies were developed to assess the synergic effects of the drugs in NPs against NCI-H661, NCI-H460, A549, H157, and H1299 lung cancer cells. The PEG/CSNPs@BTZ-VCR NPs were found to synergistically reduce the cell survival of the NCI-H661, NCI-H460, A549, H157, and H1299 cell lines, with a combined result of 0.313. The synergic effect of the BTZ and VCR was considerably more potent, with 0.22 of PEG/CSNPs@BTZ-VCR NPs. In addition, PEG/CSNPs@BTZ-VCR NPs have a higher DPPH scavenging activity (58.32%) than drug-alone. The synergistic efficiency of the PEG/CSNPs@BTZ-VCR NPs triggers apoptosis variations was detected using Calcein AM/Propidium Iodide (PI), DAPI, and PI biochemical staining techniques. Further, the apoptosis mechanism was confirmed by FITC/Annexin-V and PI staining methods. Outcomes showed that the co-delivery of bortezomib and vincristine-loaded chitosan cross-linked polymeric nanoparticles was much higher in lung cancer cells when related to free drugs.