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纳米脂质体与趋磁细菌表面的共价结合用于自推进治疗剂的合成。

Covalent binding of nanoliposomes to the surface of magnetotactic bacteria for the synthesis of self-propelled therapeutic agents.

机构信息

NanoRobotics Laboratory, Department of Computer and Software Engineering, Institute of Biomedical Engineering, Polytechnique Montréal , Montréal, Québec, Canada H3C3A7.

出版信息

ACS Nano. 2014 May 27;8(5):5049-60. doi: 10.1021/nn5011304. Epub 2014 Apr 8.

Abstract

The targeted and effective delivery of therapeutic agents remains an unmet goal in the field of controlled release systems. Magnetococcus marinus MC-1 magnetotactic bacteria (MTB) are investigated as potential therapeutic carriers. By combining directional magnetotaxis-microaerophilic control of these self-propelled agents, a larger amount of therapeutics can be delivered surpassing the diffusion limits of large drug molecules toward hard-to-treat hypoxic regions in solid tumors. The potential benefits of these carriers emphasize the need to develop an adequate method to attach therapeutic cargos, such as drug-loaded nanoliposomes, without substantially affecting the cell's ability to act as delivery agents. In this study, we report on a strategy for the attachment of liposomes to MTB (MTB-LP) through carbodiimide chemistry. The attachment efficacy, motility, and magnetic response of the MTB-LP were investigated. Results confirm that a substantial number of nanoliposomes (∼70) are efficiently linked with MTB without compromising functionality and motility. Cytotoxicity assays using three different cell types (J774, NIH/3T3, and Colo205) reveal that liposomal attachments to MTB formulation improve the biocompatibility of MTB, whereas attachment does not interfere with liposomal uptake.

摘要

在控制释放系统领域,靶向且有效的治疗剂传递仍然是一个未满足的目标。海洋磁球菌 MC-1 趋磁细菌 (MTB) 被研究为潜在的治疗载体。通过结合定向磁趋性-微需氧控制这些自推进剂,可以将更多的治疗剂递送到难以治疗的缺氧区域,超过大药物分子的扩散限制,达到实体瘤。这些载体的潜在益处强调需要开发一种适当的方法来附着治疗货物,如载药纳米脂质体,而不会实质上影响细胞作为递送剂的能力。在这项研究中,我们报告了一种通过碳二亚胺化学将脂质体附着到 MTB(MTB-LP)的策略。研究了 MTB-LP 的附着效率、迁移性和磁响应。结果证实,大量纳米脂质体(约 70 个)可以有效地与 MTB 连接,而不会损害其功能和迁移性。使用三种不同细胞类型(J774、NIH/3T3 和 Colo205)进行的细胞毒性试验表明,脂质体与 MTB 制剂的附着可以提高 MTB 的生物相容性,而附着不会干扰脂质体的摄取。

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