양경직 (연세대학교)

한빛사논문

조회256

연세대학교

CV File 450 kb

ACS Nano, Mar 06 2024, | https://doi.org/10.1021/acsnano.3c10732 Nanoengineered Polymeric RNA Nanoparticles for Controlled Biodistribution and Efficient Targeted Cancer Therapy

Taehyung Kim ¹, Hwa Seung Han², Kyungjik Yang ¹, Young Min Kim ¹, Keonwook Nam ¹, Kyung Hoon Park ¹, Seung Young Choi², Hyun Woo Park ³, Ki Young Choi ², Young Hoon Roh¹

¹Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

²Department of Marine Food Science and Technology, Gangneung-Wonju National University, 7 Jukjeon-gil, Gangneung-si, Gangwon 25457, Republic of Korea.

³Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

T.K., H.S.H., and K.Y. contributed equally to this work.

Corresponding Authors : Ki Young Choi, Young Hoon Roh

Abstract

RNA nanotechnology, including rolling circle transcription (RCT), has gained increasing interest as a fascinating siRNA delivery nanoplatform for biostable and tumor-targetable RNA-based therapies. However, due to the lack of fine-tuning technologies for RNA nanostructures, the relationship between physicochemical properties and siRNA efficacy of polymeric siRNA nanoparticles (PRNs) with different sizes has not yet been fully elucidated. Herein, we scrutinized the effects of size/surface chemistry-tuned PRNs on the biological and physiological interactions with tumors. PRNs with adjusted size and surface properties were prepared using sequential engineering processes: RCT, condensation, and nanolayer deposition of functional biopolymers. Through the RCT process, nanoparticles of three sizes with a diameter of 50-200 nm were fabricated and terminated with three types of biopolymers: poly-l-lysine (PLL), poly-l-glutamate (PLG), and hyaluronic acid (HA) for different surface properties. Among the PRNs, HA-layered nanoparticles with a diameter of ∼200 nm exhibited the most effective systemic delivery, resulting in superior anticancer effects in an orthotopic breast tumor model due to the CD44 receptor targeting and optimized nanosized structure. Depending on the type of PRNs, the in vivo siRNA delivery with protein expression inhibition differed by up to approximately 20-fold. These findings indicate that the types of layered biopolymers and the PRNs size mediate efficient polymeric siRNA delivery to the targeted tumors, resulting in high RNAi-induced therapeutic efficacy. This RNA-nanotechnology-based size/surface editing can overcome the limitations of siRNA therapeutics and represents a potent built-in module method to design RNA therapeutics tailored for targeted cancer therapy.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-03-08)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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