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Simultaneous Delivery of Dual Anticancer Agents Via pH-Responsive Polymeric Nanoparticles for Enhanced Therapeutic Efficacy Against Breast Cancer Cells

  • Muhammad Haroon,
  • Mehwish Nasim,
  • Asif Nawaz,
  • Naveed Ullah Khan,
  • Sheikh Abdur Rashid,
  • Daulat Haleem Khan,
  • Muhammad Khurshid Alam Shah,
  • Mohammad Y. Alfaifi,
  • Serag Eldin I. Elbehairi,
  • Ali A. Shati,
  • Haroon Iqbal

摘要

The stated objective of the present research investigation was to use a simultaneous nanodrug delivery approach to optimize the therapeutic effectiveness of anticancer drugs against breast cancer cells. For this purpose, Poly (lactic-co-glycolic acid) nanoparticles with two anticancer drugs; methotrexate (MTX) and doxorubicin (DOX) denoted as DOX/MTX@PLGA NPs was developed by nanoprecipitation method. The developed polymeric DOX/MTX@PLGA NPs exhibited hydrodynamic particle diameter of 170.6 ± 10.0 nm with a poly dispersity index (PDI) of 0.17 and zeta potential value of -9.2 ± 0.31 mV, and spherical geometry analyzed by TEM. Furthermore, the nanoparticles exhibited a pH-responsive drug release profile, outstanding encapsulation efficiency, excellent colloidal stability across various physiological media and pH responsive drug release profile. Additionally, polymeric nanoparticles demonstrated higher cell uptake, in-vitro cytotoxicity, and a high rate of apoptosis in comparison to free DOX and MTX through a synergistic effect, likely as a result of their small particle size. In conclusion, our work presents a novel and distinct approach for boosting the therapeutic efficacy of anticancer drugs by delivering drugs to breast cancer cells simultaneously.