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<p>Solid tumours account for more than 85% of all cancer cases, and despite significant advances in therapy, challenges such as drug resistance, systemic toxicity, and poor site specificity continue to hinder treatment success. This study aimed to develop a novel dual-drug nanoformulation of Dasatinib (DAS) and Berberine (BRB), encapsulated within (Poly(lactic-co-glycolic acid) (PLGA) and coated with a leucocyte membrane (LMc-DAS-BRB-NPs) to enhance tumour targeting and therapeutic efficacy. The optimized nanoparticles exhibited particle sizes of 151.6&#xa0;nm and 177.2&#xa0;nm, with PDI values of 0.2665 and 0.1578 for uncoated and coated formulations, respectively. The zeta potential measured − 22 mV for uncoated and − 27.22 mV for coated NPs, indicating improved stability. Entrapment efficiencies were high, at approximately 76% for DAS and 91% for BRB. Scanning Electron Microscope (SEM) and Transmission Electron Microscopy (TEM) analyses confirmed spherical morphology, a rough nanoparticle surface, and the presence of a thin leucocyte membrane coating. In vitro release studies demonstrated sustained drug release attributed to both the polymer matrix and membrane coating. Cytotoxicity studies (MTT assay on MCF-7, A431 and HCT-116 cells) showed enhanced anticancer activity of the nanoformulation compared to free drugs. DAPI (4’,6-diamidino-2-phenylindole) staining analysis demonstrated better apoptosis, shrinkage and fragmented morphology of nuclei upon treatment with the developed formulation than free drugs. Complementary molecular docking on AKT (protein kinase B), VEGFR-2 (vascular endothelial growth factor receptor 2), EGFR (epidermal growth factor receptor), and Tubulin further supported inhibitory and synergistic potential. Overall, the developed formulation offers a promising strategy for managing solid tumours.</p> Graphical Abstract <p></p>

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Leukocyte Bio-Membrane Coated PLGA-Based Nanoformulation for Co-Delivery of Dasatinib and Berberine in Solid Tumor Therapy

  • 期刊论文

  • 发表日期：

    2026年4月21日

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  • Km Rafiya,
  • Masood Nadeem,
  • Md Azhar Iqbal,
  • M. Moshahid Alam Rizvi,
  • Nazeer Hasan,
  • Farhan Jalees Ahmad

摘要

Solid tumours account for more than 85% of all cancer cases, and despite significant advances in therapy, challenges such as drug resistance, systemic toxicity, and poor site specificity continue to hinder treatment success. This study aimed to develop a novel dual-drug nanoformulation of Dasatinib (DAS) and Berberine (BRB), encapsulated within (Poly(lactic-co-glycolic acid) (PLGA) and coated with a leucocyte membrane (LMc-DAS-BRB-NPs) to enhance tumour targeting and therapeutic efficacy. The optimized nanoparticles exhibited particle sizes of 151.6 nm and 177.2 nm, with PDI values of 0.2665 and 0.1578 for uncoated and coated formulations, respectively. The zeta potential measured − 22 mV for uncoated and − 27.22 mV for coated NPs, indicating improved stability. Entrapment efficiencies were high, at approximately 76% for DAS and 91% for BRB. Scanning Electron Microscope (SEM) and Transmission Electron Microscopy (TEM) analyses confirmed spherical morphology, a rough nanoparticle surface, and the presence of a thin leucocyte membrane coating. In vitro release studies demonstrated sustained drug release attributed to both the polymer matrix and membrane coating. Cytotoxicity studies (MTT assay on MCF-7, A431 and HCT-116 cells) showed enhanced anticancer activity of the nanoformulation compared to free drugs. DAPI (4’,6-diamidino-2-phenylindole) staining analysis demonstrated better apoptosis, shrinkage and fragmented morphology of nuclei upon treatment with the developed formulation than free drugs. Complementary molecular docking on AKT (protein kinase B), VEGFR-2 (vascular endothelial growth factor receptor 2), EGFR (epidermal growth factor receptor), and Tubulin further supported inhibitory and synergistic potential. Overall, the developed formulation offers a promising strategy for managing solid tumours.

Graphical Abstract