A smart pH-responsive and sialic acid targeted hybrid nanoparticles for precise chemo-herbal delivery in lung cancer

Development of drug resistance, systemic toxicities, and treatment variability limit the translational use of nanocarriers (NCs) in lung cancer. A study utilized the successful synthesis of phenyl boronic acid-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (PBA-DOPE) with pH responsiveness and precise sialic acid targeting characteristics. PBA-DOPE was surface anchored on lipid-polymer hybrid nanoparticles (PBA-DOPE HNPs) with a higher payload (>70%) of Biochanin-A (B) and Lenvatinib (L). A lipid shell polymer core nanostructure was defined and confirmed using photon correlation spectroscopy and various high-resolution microscopic techniques. The enthalpy-driven spontaneous interactions and higher binding constants explain the strong affinity for sialic acid. The difference in particle size and drug release profile of PBA-DOPE-BL HNPs under distinct pH conditions depicted smart pH responsiveness. In vitro studies using A549 cells showed significant cytotoxicity due to higher cellular uptake with decreased mitochondrial membrane potential, which causes apoptotic cell death, in contrast to DOPE-BL HNPs and coarse-BL treated cells. PBA-DOPE-BL HNPs also produce the anti-migration and anti-proliferative effect. In vivo studies explained the superiority of PBA-DOPE-BL HNPs in terms of improving drug PK parameters, being safer, and also helping in reducing systemic toxicities of the tyrosine kinase inhibitor. Overall, PBA-DOPE-BL HNPs are biocompatible, efficient, and potential drug carriers for lung cancer applications.