유자형 (UNIST)

한빛사논문

조회103

UNIST

CV File 254 kb

J. Control. Release, Jul 16 2024, 373 S0168-3659(24)00459-0 | https://doi.org/10.1016/j.jconrel.2024.07.029 Enzyme-instructed intramitochondrial polymerization for enhanced anticancer treatment without the development of drug-resistance

Sangpil Kim, Yeji Lee, Min-Seok Seu, Youjung Sim, Ja-Hyoung Ryu

Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea

Corresponding author : Ja-Hyoung Ryu

Abstract

Intracellular polymerization in living cells motivated chemists to generate polymeric structures with a multitude of possibilities to interact with biomacromolecules. However, out-of-control of the intracellular chemical reactions would be an obstacle restricting its application, providing the toxicity of non-targeted cells. Here, we reported intracellular thioesterase-mediated polymerization for selectively occurring polymerization using disulfide bonds in cancer cells. The acetylated monomers did not form disulfide bonds even under an oxidative environment, but they could polymerize into the polymeric structure after cleavage of acetyl groups only when encountered activity of thioesterase enzyme. Furthermore, acetylated monomers could be self-assembled with doxorubicin, providing doxorubicin loaded micelles for efficient intracellular delivery of drug and monomers. Since thioesterase enzymes were overexpressed in cancer cells specifically, the micelles were disrupted under activity of the enzyme and the polymerization could occur selectively in the cancer mitochondria. The resulting polymeric structures disrupted the mitochondrial membrane, thus activating the cellular death of cancer cells with high selectivity. This strategy selectively targets diverse cancer cells involving drug-resistant cells over normal cells. Moreover, the mitochondria targeting strategy overcomes the development of drug resistance even with repeated treatment. This approach provides a way for selective intracellular polymerization with desirable anticancer treatment.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-26)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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