Intra-Lysosomal Peptide Assembly for the High Selectivity Index against Cancer
- Batakrishna JanaBatakrishna JanaDepartment of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaMore by Batakrishna Jana
- ,
- Seongeon JinSeongeon JinDepartment of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaMore by Seongeon Jin
- ,
- Eun Min GoEun Min GoSchool of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaMore by Eun Min Go
- ,
- Yumi ChoYumi ChoSchool of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaMore by Yumi Cho
- ,
- Dohyun KimDohyun KimDepartment of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaMore by Dohyun Kim
- ,
- Sangpil KimSangpil KimDepartment of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaMore by Sangpil Kim
- ,
- Sang Kyu Kwak*Sang Kyu Kwak*Email: [email protected]Department of Chemical and Biological Engineering, Korea University, Seoul 02841, Republic of KoreaMore by Sang Kyu Kwak
- , and
- Ja-Hyoung Ryu*Ja-Hyoung Ryu*Email: [email protected]Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaMore by 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.
Cited By
This article has not yet been cited by other publications.