Targeted Drug Delivery Using Smart Nanoparticles | ||
| Advances in Pharmacology and Therapeutics Journal | ||
| Volume 5, Issue 3 - Serial Number 10, Autumn 2025, Pages 143-152 PDF (754.03 K) | ||
| Document Type: Original Article | ||
| DOI: 10.18502/aptj.v5i3.20514 | ||
| Authors | ||
| Mohammad Javad Sohrabi* ; Parisa Miralinaghi; Mohammad Reza Sohrabi Renani; Fatemeh Gharishvandi | ||
| Abstract | ||
| Background: Conventional chemotherapy for cancer treatment is often limited by poor specificity, systemic toxicity, and the development of drug resistance. Targeted drug delivery systems utilizing smart nanoparticles present a promising strategy to overcome these challenges by enhancing therapeutic efficacy and minimizing off-target effects. Materials and Methods: Folate-conjugated, pH- and temperature-responsive PLGA-PEG nanoparticles encapsulating doxorubicin were synthesized via a nanoprecipitation method. The nanoparticles were characterized for their size, zeta potential, encapsulation efficiency, and drug release kinetics. Their targeting capability and cytotoxicity were evaluated in folate receptor-positive (MCF-7) and negative (NIH-3T3) cell lines using confocal microscopy, flow cytometry, and MTT assays. Furthermore, in vivo pharmacokinetics, biodistribution, antitumor efficacy, and safety were assessed in murine xenograft models. Results: The formulated nanoparticles were monodisperse (~140 nm) with high drug loading capacity and stability. Folate functionalization significantly enhanced cellular uptake in MCF-7 cells through receptor-mediated endocytosis. Drug release was minimal at physiological pH (7.4) but accelerated significantly under acidic conditions (pH 5.5) and at an elevated temperature (42°C). In vivo studies demonstrated a prolonged circulation time, higher tumor accumulation, and superior tumor growth inhibition (75% reduction) with the targeted nanoparticles compared to both free doxorubicin and non-targeted controls, alongside reduced systemic toxicity. Conclusion: The integration of active targeting with dual-stimuli responsiveness in this nanoplatform markedly enhances the precision and efficacy of doxorubicin delivery, underscoring its potential for clinical translation in precision oncology. | ||
| Keywords | ||
| Targeted Drug Delivery; PLGA-PEG Nanoparticles; Folate Receptor; Dual Stimuli Responsive; Doxorubicin | ||
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