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

  • Pharmaceutics. 2023 Feb 10;15(2):607. doi: 10.3390/pharmaceutics15020607.
Marek T Wlodarczyk  1  2 ,  Sylwia A Dragulska  1 ,  Ying Chen  3 ,  Mina Poursharifi  1  4 ,  Maxier Acosta Santiago  1 ,  John A Martignetti  3  5  6 ,  Aneta J Mieszawska  1
Affiliations
  • 1. Department of Chemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA.
  • 2. Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY 10016, USA.
  • 3. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
  • 4. Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, NY 10016, USA.
  • 5. Women's Health Research Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA.
  • 6. Rudy Ruggles Research Institute, Western Connecticut Health Network, 131 West St., Danbury, CT 06810, USA.
PMID: 36839929 DOI: 10.3390/pharmaceutics15020607
Abstract

Platinum-based agents are the main treatment option in ovarian Cancer (OC). Herein, we report a poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) encapsulating platinum (II), which is targeted to a cell-spanning protein overexpressed in above 90% of late-stage OC, Mucin 1 (MUC1). The NP is coated with phospholipid-DNA Aptamers against MUC1 and a pH-sensitive PEG derivative containing an acid-labile hydrazone linkage. The pH-sensitive PEG serves as an off-on switch that provides shielding effects at the physiological pH and is shed at lower pH, thus exposing the MUC1 ligands. The pH-MUC1-Pt NPs are stable in the serum and display pH-dependent PEG cleavage and drug release. Moreover, the NPs effectively internalize in OC cells with higher accumulation at lower pH. The Pt (II) loading into the NP was accomplished via PLGA-Pt (II) coordination chemistry and was found to be 1.62 wt.%. In vitro screening using a panel of OC cell lines revealed that pH-MUC1-Pt NP has a greater effect in reducing cellular viability than carboplatin, a clinically relevant drug analogue. Biodistribution studies have demonstrated NP accumulation at tumor sites with effective Pt (II) delivery. Together, these results demonstrate a potential for pH-MUC1-Pt NP for the enhanced Pt (II) therapy of OC and Other solid tumors currently treated with platinum agents.

Keywords
in vivo imaging; nanoparticles; ovarian cancer; pH-sensitive; platinum therapy.
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