BROWSE

Related Researcher

Author's Photo

Cho, Yoon-Kyoung
Integrated Nano-Biotech Lab (INBL)
Research Interests
  • Microfluidics, Lab-on-a-chip, personalized biomedical diagnostics, nanobioengineering

ITEM VIEW & DOWNLOAD

Targeted crystallization of mixed-charge nanoparticles in lysosomes induces selective death of cancer cells

Cited 0 times inthomson ciCited 0 times inthomson ci
Title
Targeted crystallization of mixed-charge nanoparticles in lysosomes induces selective death of cancer cells
Author
Borkowska, MagdalenaSiek, MartaKolygina, Diana V.Sobolev, Yaroslav I.Lach, SlawomirKumar, SumitCho, Yoon-KyoungKandere-Grzybowska, KristianaGrzybowski, Bartosz A.
Issue Date
2020-04
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE NANOTECHNOLOGY, v.15, no.4, pp.331 - +
Abstract
Lysosomes have become an important target for anticancer therapeutics because lysosomal cell death bypasses the classical caspase-dependent apoptosis pathway, enabling the targeting of apoptosis- and drug-resistant cancers. However, only a few small molecules-mostly repurposed drugs-have been tested so far, and these typically exhibit low cancer selectivity, making them suitable only for combination therapies. Here, we show that mixed-charge nanoparticles covered with certain ratios of positively and negatively charged ligands can selectively target lysosomes in cancerous cells while exhibiting only marginal cytotoxicity towards normal cells. This selectivity results from distinct pH-dependent aggregation events, starting from the formation of small, endocytosis-prone clusters at cell surfaces and ending with the formation of large and well-ordered nanoparticle assemblies and crystals inside cancer lysosomes. These assemblies cannot be cleared by exocytosis and cause lysosome swelling, which gradually disrupts the integrity of lysosomal membranes, ultimately impairing lysosomal functions and triggering cell death. Mixed-charge nanoparticles preferentially assemble inside the lysosomes of cancer cells, which causes lysosomal membrane disruption and lysosome-dependent cell death in cancer but not in healthy cells.
URI
https://scholarworks.unist.ac.kr/handle/201301/31967
URL
https://www.nature.com/articles/s41565-020-0643-3
DOI
10.1038/s41565-020-0643-3
ISSN
1748-3387
Appears in Collections:
PHY_Journal Papers
BME_Journal Papers
Files in This Item:
There are no files associated with this item.

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record

qrcode

  • mendeley

    citeulike

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

MENU