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Borkowska, Magdalena
첨단연성물질 연구단
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Targeted crystallization of mixed-charge nanoparticles in lysosomes induces selective death of cancer cells

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Title
Targeted crystallization of mixed-charge nanoparticles in lysosomes induces selective death of cancer cells
Author(s)
Magdalena Borkowska; Marta Siek; Diana V. Kolygina; Yaroslav I. Sobolev; Slawomir Lach; Sumit Kumar; Yoon-Kyoung Cho; Kristiana Kandere-Grzybowska; Bartosz A. Grzybowski
Subject
CELLULAR UPTAKE, ; GOLD NANOPARTICLES, ; SURFACE-CHARGE, ; SPHINGOLIPID METABOLISM, ; CYTOTOXICITY, ; AGGREGATION, ; TRAFFICKING, ; PENETRATION, ; MONOLAYERS, ; MOLECULES
Publication Date
2020-04
Journal
NATURE NANOTECHNOLOGY, v.15, no.4, pp.331 - 341
Publisher
NATURE PUBLISHING GROUP
Abstract
© 2020, The Author(s), under exclusive licence to Springer Nature Limited. 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.
URI
https://pr.ibs.re.kr/handle/8788114/8698
DOI
10.1038/s41565-020-0643-3
ISSN
1748-3387
Appears in Collections:
Center for Soft and Living Matter(첨단연성물질 연구단) > 1. Journal Papers (저널논문)
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