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- 조회390
Small, Nov 22 2023, | https://doi.org/10.1002/smll.202308872
Drug-Loaded Nanogel for Efficient Orchestration of Cell Death Pathways by Intramitochondrial Disulfide Polymerization
Eun Seong Choi 1, Sangpil Kim 1, Dohyun Kim 1, Eunshil Choi 1, Ja-Hyoung Ryu 1
1Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
CORRESPONDING AUTHORS : Eunshil Choi, Ja-Hyoung Ryu
Abstract
Chemotherapy using a nanoscaled drug delivery system is an effective cancer therapy, but its high drug concentration often causes drug resistance in cancer cells and normal cell damage. Combination therapy involving two or more different cell signaling pathways can be a powerful tool to overcome the limitations of chemotherapy. Herein, this article presents nanogel (NG)-mediated co-delivery of a chemodrug camptothecin (CPT) and mitochondria-targeting monomer (MT monomer) for efficient activation of two modes of the programmed cell death pathway (apoptosis and necroptosis) and synergistic enhancement of cancer therapy. CPT and the monomer are incorporated together into the redox-degradable polymeric NGs for release in response to the intracellular glutathione. The MT monomer is shown to undergo reactive oxygen species (ROS)-triggered disulfide polymerization inside the cancerous mitochondria in cooperation with the chemotherapeutic CPT elevating the intracellular ROS level. The CPT/monomer interconnection in cell death mechanisms for mitochondrial dysfunction and enhanced cell death is evidenced by a series of cell analyses showing ROS generation, mitochondria damage, impacts on (non)cancerous or drug-resistant cells, and cell death modes. The presented work provides beneficial insights for utilizing combination therapy to facilitate a desired cell death mechanism and developing a novel nanosystem for more efficacious cancer treatment.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2023-11-27)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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