Lee Gyeong Won, Kim Byeongyeon, Lee Tae Wook, Yim Sang-Gu, Chandrasekharan Ajeesh, Kim Hyewon, Choi Sungyoung, Yang Seung Yun
Department of Biomaterials Science (BK21 Four Program) Pusan National University Miryang South Korea.
Department of Biomedical Engineering, Department of Electronic Engineering, Hanyang Institute of Bioscience and Biotechnology Hanyang University Seoul South Korea.
Bioeng Transl Med. 2022 Dec 8;8(4):e10418. doi: 10.1002/btm2.10418. eCollection 2023 Jul.
The exogenous control of intracellular drug delivery has been shown to improve the overall efficacy of therapies by reducing nonspecific off-target toxicity. However, achieving a precise on-demand dosage of a drug in deep tissues with minimal damage is still a challenge. In this study, we report an electric-pulse-driven nanopore-electroporation (nEP) system for the localized intracellular delivery of a model agent in deep tissues. Compared with conventional bulk electroporation, in vitro nEP achieved better transfection efficiency (>60%) with a high cell recovery rate (>95%) under a nontoxic low electroporation condition (40 V). Furthermore, in vivo nEP using a nanopore needle electrode with a side drug-releasing compartment offered better control over the dosage release, time, and location of propidium iodide, which was used as a model agent for intracellular delivery. In a pilot study using experimental animals, the nEP system exhibited two times higher transfection efficiency of propidium iodide in the thigh muscle tissue, while minimizing tissue damage (<20%) compared to that of bulk electroporation. This tissue-penetrating nEP platform can provide localized, safe, and effective intracellular delivery of diverse therapeutics into deep tissues in a controlled manner.
细胞内药物递送的外部控制已被证明可通过降低非特异性脱靶毒性来提高治疗的整体疗效。然而，在对深层组织造成最小损伤的情况下实现药物的精确按需给药仍然是一项挑战。在本研究中，我们报告了一种电脉冲驱动的纳米孔电穿孔（nEP）系统，用于在深层组织中对模型药物进行局部细胞内递送。与传统的大容量电穿孔相比，体外nEP在无毒的低电穿孔条件（40 V）下实现了更高的转染效率（>60%）和高细胞回收率（>95%）。此外，使用带有侧面药物释放隔室的纳米孔针电极进行体内nEP，能够更好地控制用作细胞内递送模型药物的碘化丙啶的剂量释放、时间和位置。在一项使用实验动物的初步研究中，与大容量电穿孔相比，nEP系统在大腿肌肉组织中碘化丙啶的转染效率高出两倍，同时将组织损伤降至最低（<20%）。这种可穿透组织的nEP平台能够以可控的方式将多种治疗药物局部、安全且有效地递送至深层组织的细胞内。
Zotero 插件
