Journal
ADVANCED HEALTHCARE MATERIALS
Volume 8, Issue 12, Pages -Publisher
WILEY
DOI: 10.1002/adhm.201801511
Keywords
autophagic flux; insulin secretion; lipotoxicity; lysosomal acidification; PLGA nanoparticles
Funding
- Boston University (BU) Nano Crossdisciplinary fellowship from the BU Nano center at Boston University
- National Institutes of Health [R01 DK099618]
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Chronic exposure to high levels of fatty acids (lipotoxicity) in pancreatic beta cells (beta-cells) decreases lysosomal acidity and inhibits autophagic flux. Today, there are a lack of approaches to modify lysosomal acidity to determine whether impaired lysosomal acidification is causally inhibiting autophagic flux and cellular functions. Biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) with diameters of approximate to 100 nm localize to lysosomes and serve as an ideal method to deliver lactic and glycolic acid to lysosomes upon NP polymer degradation. In this study, the ability of PLGA NPs to lower lysosomal pH and restore autophagic flux is investigated in pancreatic insulin secreting (INS1) beta-cells. PLGA NPs display a concentration dependent performance with higher concentrations of PLGA NPs, lowering lysosomal pH, as well as restoring autophagic flux and insulin secretion in pancreatic beta-cells. These results document that acidifying the lysosome, via an external perturbation, in lipotoxic pancreatic beta-cells affords a specific biological outcome of improved cellular degradative activity.
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