Browsing by Author "Manjit Saini"

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Crafting a Molecular Trojan Horse: Sialic Acid-Modified PLGA Nanoparticles for Targeted Lung Cancer Therapy
(American Chemical Society, 2025) Krishan Kumar; Manjit Saini; Varsha Rani; Mohini Mishra; None Priya; None Jatin; Siddharth Tiwari; Brahmeshwar Mishra; Ruchi Chawla
The glycan receptors prominently expressed on the surface of lung cancer cells offers promising targets for drug delivery. The prepared gemcitabine (GB)-loaded PLGA-NPs and sialic acid (Siac)-modified PLGA-NPs exhibited a uniform polydispersity index (PDI) value below 0.3, a particle size under 200 nm, and negative zeta potentials ranging from −17.45 to −21.45 mV. Entrapment efficiency (% EE) and drug loading values exceeded 70% and 8%, respectively. SEM and TEM showed that the particles were uniformly dispersed with a spherical shape. FTIR, XRD, TGA, and DSC analyses indicated the physiochemical stability of the drug within the nanoformulations. Controlled (26.92 to 31.64% within 24 h at pH 7.4) and pH-sensitive (36.80 to 40.25% within 24 h at pH 5.5) GB release were observed for the different formulations of PLGA-NPs. The MTT cytotoxicity assay revealed IC50 values for the GB control, GB-PLGA-NPs, and GB-PLGA-Siac-NPs as 13.65 ± 1.20, 8.14 ± 1.24, and 4.16 ± 1.05 μg/mL, respectively. The Co6-GB-PLGA-Siac-NPs showed significantly higher cellular uptake than that of the Co6-GB control (p < 0.001) and Co6-GB-PLGA-NPs (p < 0.01) respectively. Pharmacokinetic profiles indicated higher AUC values (ng·h/mL) for GB-PLGA-Siac-NPs (8355.07 ± 2006.45) compared to GB-PLGA-NPs (6145.58 ± 969.25) and the GB control (1510.72 ± 81.08), resulting in higher bioavailability of GB-PLGA-Siac-NPs. Biodistribution studies confirmed superior localization of DiD-GB-PLGA-Siac-NPs, indicated by radiant efficiency signal on B[a]P induced lung cancerous tissues relative to DiD-GB-PLGA-NPs after 1 h (p < 0.001), 4 h (p < 0.01), and 12 h (p < 0.001), which could be attributed to their ability to target glycans. In vivo anticancer efficacy in a B[a]P-induced lung cancer mice model depicted that GB-PLGA-Siac-NPs effectively inhibited lung cancer cells and reduced systemic toxicity, as evidenced by the average number of lung cancer cells, body weight values, survival analysis, biochemical parameters associated with organs (such as the liver and kidney), and histopathological analysis. Therefore, GB-loaded Siac-coated PLGA nanoparticles could serve as an efficient vehicle for GB delivery via targeting glycan receptors in lung cancer therapy. © 2025 American Chemical Society.