Targeted Drug Delivery Using Smart Nanoparticles

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-۷) and negative (NIH-۳T۳) 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 (~۱۴۰ nm) with high drug loading capacity and stability. Folate functionalization significantly enhanced cellular uptake in MCF-۷ cells through receptor-mediated endocytosis. Drug release was minimal at physiological pH (۷.۴) but accelerated significantly under acidic conditions (pH ۵.۵) and at an elevated temperature (۴۲°C). In vivo studies demonstrated a prolonged circulation time, higher tumor accumulation, and superior tumor growth inhibition (۷۵% 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.

کلیدواژه ها:

targeted drug delivery ، PLGA-PEG nanoparticles ، folate receptor ، dual stimuli responsive ، doxorubicin