ArticlePharmaceutical research2026
Design, Synthesis and Characterization of Anti-CTLA4 Peptide Conjugated Gemcitabine Prodrug Nanoparticles for Targeted Lung Cancer Chemoimmunotherapy.
Article in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveLung cancer continues to be a major contributor to global cancer mortality due to extensive tumor heterogeneity, drug resistance, and limited efficacy of conventional therapies. To address these limitations, the present study aimed on rational design and development of anti-CTLA4 peptide-conjugated gemcitabine prodrug nanoparticles (PD-NPs) for targeted lung cancer chemoimmunotherapy.
methodPD-NPs was synthesized by conjugating an anti-CTLA4 peptide (ARHPSWYRPFEGCG), a cathepsin B cleavable linker (FRRG) to the free amino group of gemcitabine via a single step amide bond formation, enabling the formation of stable self-assemble PD-NPs. In-silico evaluation was carried out by molecular docking study, while physicochemical properties were confirmed through different spectroscopical analyses. In-vitro studies, including cell viability, clonogenic, scratch, and apoptosis assay by flow cytometry were performed in A549 and NCI-H460 cell lines. In-vivo toxicity and biodistribution study were conducted to determine therapeutic doses. Subsequently chemoimmunotherapeutic efficacy of PD-NPs was evaluated in B16-F10 induced lung tumor mice model.
resultsPD-NPs exhibited a zeta potential of ± 34.4 mV, an average particle size of 229.8 ± 2.1 nm, and polydispersity index 0.2, suggesting a stable and monodisperse formulation. In vitro studies demonstrated potent cytotoxic effect, suppression of clonogenicity, inhibition of cellular migration, apoptosis induction, and inhibition of carcinogenic protein expression. In vivo treatment resulted in significant tumor regression, restoration of lung tissue architecture, activating CD8 expression, and altering TNF-α expression following PD-NPs treatment.
conclusionOverall, these findings highlight the therapeutic potential of enzyme responsive, anti-CTLA4 peptide conjugated gemcitabine prodrug nanoparticles as a promising strategy for targeted lung cancer chemoimmunotherapy.
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