한빛사논문
- 조회657
Batakrishna Jana 1 †, Seongeon Jin 1 †, Eun Min Go 2, Yumi Cho 2, Dohyun Kim 1, Sangpil Kim 1, Sang Kyu Kwak 3 *, Ja-Hyoung Ryu 1 *
1Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
2School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
3Department of Chemical and Biological Engineering, Korea University, Seoul 02841, Republic of Korea.
†B.J. and S.J. contributed equally to this work.
*Corresponding author: correspondence to Sang Kyu Kwak or Ja-Hyoung Ryu
Abstract
Lysosomes remain powerful organelles and important targets for cancer therapy because cancer cell proliferation is greatly dependent on effective lysosomal function. Recent studies have shown that lysosomal membrane permeabilization induces cell death and is an effective way to treat cancer by bypassing the classical caspase-dependent apoptotic pathway. However, most lysosome-targeted anticancer drugs have very low selectivity for cancer cells. Here, we show intra-lysosomal self-assembly of a peptide amphiphile as a powerful technique to overcome this problem. We designed a peptide amphiphile that localizes in the cancer lysosome and undergoes cathepsin B enzyme-instructed supramolecular assembly. This localized assembly induces lysosomal swelling, membrane permeabilization, and damage to the lysosome, which eventually causes caspase-independent apoptotic death of cancer cells without conventional chemotherapeutic drugs. It has specific anticancer effects and is effective against drug-resistant cancers. Moreover, this peptide amphiphile exhibits high tumor targeting when attached to a tumor-targeting ligand and causes significant inhibition of tumor growth both in cancer and drug-resistant cancer xenograft models.
논문정보
- Research article
- 2023년 07월 (BRIC 등록일 2023-08-09)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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