Biopolym. Cell. 2026; 42(1):54-67.
https://doi.org/10.7124/bc.000B2E
Molecular and Cell Biotechnologies
Doxorubicin-PLGA nanoparticles are immunomodulational antitumor therapeutics with dual cytotoxic and immune-stimulatory effects
1Jaaffer M. D., 1Chaloop A. M.
  1. College of Energy and Environmental Sciences, Al-Karkh University of Science
    Baghdad, Iraq

Abstract

Aim. The aim of this study is to investigate the immunomodulatory and antitumor effects of doxorubicin-loaded poly(lactic-co-glycolic acid) nanoparticles (DOX-PLGA NPs) designed as a dual-function nano-immunotherapeutic system. Methods. DOX-PLGA NPs were synthesized by the emulsion-solvent evaporation method and characterized for particle size, zeta potential, morphology (TEM), drug loading, and release behavior. The cytotoxicity of free DOX and DOX-PLGA NPs was evaluated in MCF-7 and HCT116 cancer cell lines using the MTT assay. «Peripheral blood mononuclear cell (PBMC) — tumor» co-cultures were analyzed for cytokine secretion (IFN-γ, IL-2, TNF-α, and IL-10) and immune cell subsets (CD8+ T-cells, NK cells, and macrophage polarization). The therapeutic efficacy was further examined in CT26 tumor-bearing mice. Results. The DOX-PLGA NPs exhibited a mean size of approximately 145 nm (PDI 0.18, ζ −22 mV), with a drug loading efficiency of 12.5% and encapsulation efficiency of 78%. In comparison to free DOX, the nano-formulation lowered cell viability to a greater extent (p < 0.01) and stimulated greater release of IFN-γ, IL-2, and TNF-α, while IL-10 levels decreased. Flow cytometric analysis shows increases in the populations of CD8+ T and NK cells and a congruent macrophage reversal to the M1 macrophage phenotype. Tumor growth was markedly suppressed, survival was extended, and DOX-PLGA NPs produced insignificant systemic toxicity in the in vivo setting. Conclusions. The immuno-nanoparticles demonstrate controlled release of DOX-PLGA NPs while maintaining powerful immune stimulation due to the dual cytotoxic and immunostimulatory effects they exhibit. Their application as a novel platform for nano-immunotherapy in the treatment of cancer is justified.
Keywords: DOX-loaded PLGA nanoparticles, PLGA, nano-immunotherapy, cytokines, immune activation, cancer therapy,
Full text: (PDF, in English)

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