김성찬 (한국과학기술연구원)

한빛사논문

조회180

한국과학기술연구원

Adv. Healthc. Mater., Jul 31 2024, | https://doi.org/10.1002/adhm.202400240 Improvement of Therapeutic Effect via Inducing Non-Apoptotic Cell Death Using mRNA-Protection Nanocage

Seoyoung Kim ¹, Seongchan Kim ^1,2,3, Sojin Kim ^4,5, Nan-Ee Lee ¹, Soo-Hwan Lee ¹, Hyunkyung Kim^4,5, Hyojin Lee ^1,6,7

¹Biomaterial Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.

²Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.

³College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Gyeongsangnam-do, 52828, Republic of Korea.

⁴Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841, Republic of Korea.

⁵BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, 02841, Republic of Korea.

⁶Division of Bio-Medical Science & Technology, Korea National University of Science and Technology (UST), Seoul, 02792, Republic of Korea.

⁷SKKU-KIST, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi, 16419, Republic of Korea.

S.K. and S.K. contributed equally to this work.

Corresponding Authors: Hyunkyung Kim, Hyojin Lee

Abstract

Necroptosis, a cell death mechanism with the characteristics of both apoptosis and necrosis, is proposed as a promising therapeutic approach for cancer therapy. Induction of necroptosis for cancer therapy may be possible through the regulation of the expression of a key factor gene receptor-interacting protein kinase-3 (RIPK3) via in vitro transcription (IVT) mRNA delivery. However, mRNA is susceptible to degradation and has a low delivery efficiency, which highlights the requirement of a proper delivery vehicle for intracellular delivery. Therefore, a new mRNA delivery system based on the nanostructured silica nanoparticles, termed mRNA-protective nanocage (mPN) has been developed. High-efficiency expression of RIPK3 and induction of necroptosis is achieved through delivery of RIPK3 IVT mRNA with mPN in vitro and in vivo models. Importantly, the mPN carrying RIPK3 mRNA distributed locally in tumors upon intravascular injection, and successfully induced necroptosis and immune cell infiltration, a hallmark of necroptosis. the suppression of tumor growth in a murine cancer model, demonstrating the synergistic effect of RIPK3 mRNA- and immune cell-mediated therapy is also observed. These findings suggest the potential for anticancer therapy through necroptosis induction and provide a strategy for the development of mRNA-based nanomedicine.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-08-05)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

댓글 작성 로그인

CV 열람하기

연락처 보기