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Targeted drug delivery using smart nanoparticles | ||
| Advances in Pharmacology and Therapeutics Journal | ||
| Articles in Press, Accepted Manuscript, Available Online from 28 October 2025 PDF (754.96 K) | ||
| Document Type: Original Article | ||
| Authors | ||
| Mohammad Javad Sohrabi* 1; Parisa Miralinaghi2; Mohammad Reza Sohrabi Renani3; Fatemeh Gharishvandi4 | ||
| 1Department of Pharmacology, Faculty of Pharmaceutical, Damghan, Iran | ||
| 2Department of Medical chemistry, Faculty of Pharmaceutical, Damghan Islamic Azad University, Damghan, Iran | ||
| 3Department of medicine, Faculty of medicine, Guilan University of Medical Sciences, Rasht, Iran | ||
| 4Department of Clinical Biochemistry, School of Medicine,Tehran University of Medical Sciences, Tehran, Iran | ||
| Abstract | ||
| The development of targeted drug delivery systems using smart nanoparticles offers a transformative approach to cancer treatment by improving therapeutic efficacy and minimizing off-target toxicity. In this study, we report the design, synthesis, and evaluation of folate-conjugated, pH- and temperature-responsive PLGA-PEG nanoparticles encapsulating doxorubicin for selective cancer therapy. The nanoparticles were synthesized via nanoprecipitation and characterized for particle size, morphology, zeta potential, drug encapsulation efficiency, and release kinetics under physiological and tumor-mimicking conditions. Targeting capability was assessed in folate receptor-positive (MCF-7) and negative (NIH-3T3) cells using confocal microscopy and flow cytometry. Cytotoxicity was measured using MTT assays, while in vivo pharmacokinetics, biodistribution, tumor suppression, and histopathology were analyzed in murine xenograft models. Results showed monodisperse nanoparticles (~140 nm, negative surface charge) with high drug loading and stability. Folate-functionalization significantly enhanced cellular uptake in MCF-7 cells compared to non-targeted particles. Drug release was minimal at physiological pH (7.4) but accelerated at acidic pH (5.5) and elevated temperature (42°C), simulating tumor conditions. In vivo studies revealed extended circulation time, higher tumor accumulation, and greater tumor growth inhibition with reduced systemic toxicity compared to free doxorubicin. Histological analysis confirmed selective tumor apoptosis without damage to major organs. This work highlights the synergistic benefit of combining active targeting and dual-stimuli responsiveness in a single nanoplatform, supporting its potential for clinical translation in precision oncology. The platform could be further adapted for combination therapies or integrated with diagnostic agents for theranostic applications. | ||
| Keywords | ||
| targeted drug delivery; PLGA-PEG nanoparticles; folate receptor; dual stimuli responsive; doxorubicin | ||
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