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Pt(II)-PLGA Hybrid in a pH-Responsive Nanoparticle System Targeting Ovarian Cancer.

Marek T Wlodarczyk1,2, Sylwia A Dragulska1, Ying Chen3

  • 1Department of Chemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA.

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We developed a novel nanoparticle for ovarian cancer (OC) therapy. This targeted drug delivery system shows enhanced platinum (II) efficacy against OC cells compared to standard treatments.

Keywords:
in vivo imagingnanoparticlesovarian cancerpH-sensitiveplatinum therapy

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Platinum-based chemotherapy is a cornerstone treatment for ovarian cancer (OC).
  • Targeted drug delivery systems aim to improve therapeutic efficacy and reduce side effects.
  • Mucin 1 (MUC1) is a cell-surface protein overexpressed in late-stage OC, making it a viable therapeutic target.

Purpose of the Study:

  • To develop and evaluate a novel poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) encapsulating platinum (II) for targeted OC therapy.
  • To engineer the NP with MUC1-targeting aptamers and a pH-sensitive coating for enhanced drug delivery.
  • To assess the efficacy and biodistribution of the pH-MUC1-Pt NP in OC models.

Main Methods:

  • Synthesis of PLGA nanoparticles loaded with platinum (II) (Pt(II)).
  • Functionalization of NPs with MUC1-targeting DNA aptamers and a pH-sensitive PEG derivative.
  • In vitro evaluation of NP stability, drug release kinetics, cellular uptake, and cytotoxicity in OC cell lines.
  • In vivo biodistribution studies to assess NP accumulation at tumor sites.

Main Results:

  • The pH-MUC1-Pt NPs demonstrated pH-dependent cleavage of the PEG layer and controlled release of Pt(II).
  • NPs showed enhanced internalization and accumulation in OC cells, particularly at lower pH.
  • In vitro studies indicated superior cytotoxicity of pH-MUC1-Pt NPs compared to carboplatin.
  • Biodistribution studies confirmed NP accumulation in tumors and effective delivery of Pt(II).

Conclusions:

  • The developed pH-MUC1-Pt NP is a promising platform for targeted platinum (II) delivery in ovarian cancer.
  • This targeted nanoparticle system offers potential for enhanced efficacy in treating OC and other solid tumors.
  • The pH-sensitive and MUC1-targeting features contribute to improved therapeutic outcomes in preclinical models.