2. Academic Validation
  3. Biodegradable PLGA nanoparticles restore lysosomal acidity and protect neural PC-12 cells against mitochondrial toxicity

Biodegradable PLGA nanoparticles restore lysosomal acidity and protect neural PC-12 cells against mitochondrial toxicity

  • Ind Eng Chem Res. 2019 Aug 7;58(31):13910-13917. doi: 10.1021/acs.iecr.9b02003.
Jialiu Zeng 1,  Andrew Martin 1,  Xue Han 1,  Orian S Shirihai 2 3,  Mark W Grinstaff 1 3 4
Affiliations

Affiliations

  • 1 Department of Biomedical Engineering, Boston University, Boston, MA 02215, United States.
  • 2 Division of Endocrinology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90045, United States.
  • 3 Department of Medicine, Boston University School of Medicine, Boston, MA 02118, United States.
  • 4 Department of Chemistry, Boston University, Boston, MA 02215, United States.
PMID: 38576774 DOI: 10.1021/acs.iecr.9b02003
Abstract

Exposure of mitochondrial parkinsonian neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) to PC-12 cells results in significant cell death, decreases lysosomal acidity, and inhibits autophagic flux. Biodegradable poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) of ≈100 nm diameter localize to the lysosome, degrade, and subsequently release their acidic components to acidify the local lysosomal environment. The performance of PLGA NPs with different lysosomal pH modulating capabilities is investigated in PC-12 cells under MPP+ induced mitochondrial toxicity. PLGA NPs perform in a compositional dependent manner, where NPs with a higher glycolic acid to lactic acid ratio content degrade faster, and yield greater degrees of lysosomal pH modulation as well as autophagic flux modulation in PC-12 cells under MPP+ insult. These results show that slight compositional changes of the polymeric NP give rise to differing degrees of lysosomal acidification in PC-12 cells and afford improved cellular degradative activity.

Keywords

Autophagic flux; Lysosomal acidification; MPP+; PC-12 cells; PLGA nanoparticles; Parkinson’s disease.

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