한빛사논문
- 조회138
Taewon Jeon1, Ritabrita Goswami2, Harini Nagaraj2, Yagiz Anil Cicek2, Victor Lehot2, Janelle Welton3, Charlotte J. Bell3, Jungmi Park2, David C. Luther2, Jungkyun Im4, Caren M. Rotello5, Jesse Mager6, Vincent M. Rotello2,7*
1Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, 230 Stockbridge Road, Amherst, MA, 01003 USA
2Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA, 01003 USA
3Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, 661 N Pleasant Street, Amherst, MA, 01003 USA
4Department of Chemical Engineering, and Department of Electronic Materials, Devices, and Equipment Engineering, Soonchunhyang University, 22 Soonchunhyangro, Asan, 31538 Republic of Korea
5Department of Psychological and Brain Science, University of Massachusetts, 135 Hicks Way, Amherst, MA, 01003 USA
6Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, 661 N Pleasant Street, Amherst, MA, 01003 USA
7Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, 230 Stockbridge Road, Amherst, MA, 01003 USA
T.J. and R.G. contributed equally to this work.
*Corresponding Author : Vincent M. Rotello
Abstract
Self-assembly of small interfering RNA (siRNA) with a block copolymer featuring guanidinium and zwitterion functionalized blocks generates core-shell-like nanovectors that provide cytosolic access to siRNA and efficiently evade phagocytic clearance. The guanidinium-functionalized inner block complexes siRNA in the nanovector interior and enables cytosolic delivery. The zwitterionic outer block provides a non-interacting shell on the nanovectors that reduces macrophage uptake in vitro and phagocytic clearance and enhances tumor localization in vivo. These nanovectors are used to treat a 4T1 (murine) model of triple-negative breast cancer (TNBC). The nanovectors deliver siRNA efficiently to 4T1 triple-negative breast cancer cells in vitro, with high selectivity relative to macrophages. This efficiency and selectivity translate into in vivo efficacy: diblock nanovectors evaded phagocytic clearance and efficiently localized in an aggressive murine 4T1 orthotopic model, with a ≈3-fold increase of vector residing in the tumor compared to the homopolymer nanovectors. This increased localization efficiently knocked down STAT3 (≈80%) and provided tumorostasis (100% growth inhibition) at a low dose of 0.14 mg kg−1. The in vitro and in vivo efficacy of these nanovectors demonstrate the potential of engineered polymer architectures to generate effective self-assembled siRNA therapeutics that avoid phagocytic clearance for the treatment of diseases requiring systemic administration.
논문정보
- Research article
- 2024년 08월 (BRIC 등록일 2024-08-19)
- 국내+국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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