NanoRobotics Laboratory, Department of Computer and Software Engineering, Institute of Biomedical Engingeering, Polytechnique Montréal, Montréal H3T 1J4, Canada.
Department of Biomedical Engineering, McGill University, Montréal H3A 2B4, Canada.
Nat Nanotechnol. 2016 Nov;11(11):941-947. doi: 10.1038/nnano.2016.137. Epub 2016 Aug 15.
Oxygen-depleted hypoxic regions in the tumour are generally resistant to therapies. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour of magnetotactic bacteria, Magnetococcus marinus strain MC-1 (ref. 4), can be used to transport drug-loaded nanoliposomes into hypoxic regions of the tumour. In their natural environment, MC-1 cells, each containing a chain of magnetic iron-oxide nanocrystals, tend to swim along local magnetic field lines and towards low oxygen concentrations based on a two-state aerotactic sensing system. We show that when MC-1 cells bearing covalently bound drug-containing nanoliposomes were injected near the tumour in severe combined immunodeficient beige mice and magnetically guided, up to 55% of MC-1 cells penetrated into hypoxic regions of HCT116 colorectal xenografts. Approximately 70 drug-loaded nanoliposomes were attached to each MC-1 cell. Our results suggest that harnessing swarms of microorganisms exhibiting magneto-aerotactic behaviour can significantly improve the therapeutic index of various nanocarriers in tumour hypoxic regions.
肿瘤中缺氧的缺氧区域通常对治疗有抗性。尽管已经使用纳米载体来递送药物,但靶向比率非常低。在这里,我们表明趋磁细菌 Magnetococcus marinus 菌株 MC-1(参考文献 4)的磁气趋性迁移行为可用于将载药纳米脂质体输送到肿瘤的缺氧区域。在其自然环境中,每个含有链状磁性氧化铁纳米晶体的 MC-1 细胞都倾向于根据双态趋氧感应系统沿着局部磁场线和低氧浓度游动。我们表明,当在严重联合免疫缺陷 beige 小鼠的肿瘤附近注射携带共价结合的含药纳米脂质体的 MC-1 细胞并进行磁引导时,多达 55%的 MC-1 细胞穿透到 HCT116 结直肠异种移植瘤的缺氧区域。大约有 70 个载药纳米脂质体附着在每个 MC-1 细胞上。我们的结果表明,利用表现出磁气趋性行为的微生物群可以显著提高各种纳米载体在肿瘤缺氧区域的治疗指数。