Heterochiral Assembly of Amphiphilic Peptides Inside the Mitochondria for Supramolecular Cancer Therapeutics

Authors
Jeena, M. T.Jeong, KeunsooGo, Eun MinCho, YuriLee, SeokyungJin, SeongeonHwang, Suk-WonJang, Joo HeeKang, Chi SooBang, Woo-YoungLee, EunjiKwak, Sang KyuKim, SehoonRyu, Ja-Hyoung
Issue Date
2019-10
Publisher
AMER CHEMICAL SOC
Citation
ACS NANO, v.13, no.10, pp.11022 - 11033
Abstract
Self-assembly of peptides containing both L- and D-isomers often results in nanostructures with enhanced properties compared to their enantiomeric analogues, such as faster kinetics of formation, higher mechanical strength, and enzymatic stability. However, occurrence and consequences of the heterochiral assembly in the cellular microenvironment are unknown. In this study, we monitored heterochiral assembly of amphiphilic peptides inside the cell, specifically mitochondria of cancer cells, resulting in nanostructures with refined morphological and biological properties owing to the superior interaction between the backbones of opposite chirality. We have designed a mitochondria penetrating tripeptide containing a diphenyl alanine building unit, named as Mito-FF due to their mitochondria targeting ability. The short peptide amphiphile, Mito-FF co-assembled with its mirror pair, Mito-ff, induced superfibrils of around 100 nm in diameter and 0.5-1 mu m in length, while enantiomers formed only narrow fibers of 10 nm in diameter. The co-administration of Mito-FF and Mito-ff in the cell induced drastic mitochondrial disruption both in vitro and in vivo. The experimental and theoretical analyses revealed that pyrene capping played a major role in inducing superfibril morphology upon the co-assembly of racemic peptides. This work shows the impact of chirality control over the peptide self-assembly inside the biological system, thus showing a potent strategy for fabricating promising peptide biomaterials by considering chirality as a design modality.
Keywords
D-AMINO-ACID; BETA-SHEET; TARGETING MITOCHONDRIA; CELLULAR UPTAKE; CONJUGATION; STABILITY; MOLECULES; DRIVEN; CELLS; D-AMINO-ACID; BETA-SHEET; TARGETING MITOCHONDRIA; CELLULAR UPTAKE; CONJUGATION; STABILITY; MOLECULES; DRIVEN; CELLS; heterochiral assembly; intramitochondrial; supramolecular therapy; self-assembly
ISSN
1936-0851
URI
https://pubs.kist.re.kr/handle/201004/119524
DOI
10.1021/acsnano.9b02522
Appears in Collections:
KIST Article > 2019
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