Magnetosome-inspired synthesis of soft ferrimagnetic nanoparticles for magnetic tumor targeting.

Magnetosome-inspired synthesis of soft ferrimagnetic nanoparticles for magnetic tumor targeting.
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磁小体启发合成软亚铁磁性纳米颗粒用于磁性肿瘤靶向

DOI:
10.1073/pnas.2211228119
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发表时间:
2022-11-08
影响因子:
11.1
通讯作者:
--
中科院分区:
综合性期刊1区
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纳米药物的磁性靶向给药已成为肿瘤显像和药物治疗的最有前途的手段之一。受趋磁细菌(MTB)中磁小体生物矿化的启发,本研究通过将Mms 6蛋白整合到反胶束体系中,构建了一个类似于磁小体的仿生纳米反应器。在这种磁小体激发的纳米腔室中合成了具有单畴结构的磁小体状磁性纳米颗粒。随后对它们的形态和磁性进行了表征,并与AMB-1 MTB产生的天然磁小体进行了比较。磁小体样MNP的小尺寸和其由软铁磁性产生的强磁靶向能力将肿瘤穿透提高了一个数量级,在肿瘤区域显示出正对比。磁靶向是提高靶向效率的最有前途的方法之一,通过该方法,磁性药物载体利用外部磁场被引导到达其靶点。磁小体是趋磁细菌(MTB)体内通过生物矿化作用形成的一种特殊的“细胞器”,是生物体产生的一种天然磁性纳米粒子(MNP),是MTB响应地磁场进行磁导航的关键。然而,磁小体的磁性靶向作用会受到磁小体在水和生物流体环境中由于颗粒之间的强磁性吸引而聚集和沉淀的阻碍。在这项研究中,我们构建了一个磁小体样纳米反应器,通过引入MTB Mms 6蛋白到反胶束系统。通过热分解合成的MNP表现出与天然磁小体相同的晶体形态和磁性(高饱和磁化强度和低磁化率),但具有较小的颗粒尺寸。DSPE-mPEG包被的磁小体样MNP表现出良好的单分散性,穿透肿瘤小鼠模型的病变区域,实现比对照组高一个数量级的磁性富集,展示了生物医学磁靶向应用的巨大前景。
Magnetic targeted delivery of nanoparticle drugs has become one of the most promising means of tumor imaging and drug therapy. Inspired by magnetosome biomineralization in magnetotactic bacteria (MTB), in this study, we construct a biomimetic nanoreactor similar to that of the magnetosome by integrating Mms6 protein into a reverse micelle system. The magnetosome-like magnetic nanoparticles (MNPs) with a single domain were synthesized in this magnetosome-inspired nanoscale chamber. Their morphology and magnetic property were subsequently characterized and compared with the natural magnetosomes produced by AMB-1 MTB. The small size of magnetosome-like MNPs and their strong magnetic targeting ability produced by soft ferromagnetism improved the tumor penetration by an order of magnitude, showing a positive contrast in the tumor area. Magnetic targeting is one of the most promising approaches for improving the targeting efficiency by which magnetic drug carriers are directed using external magnetic fields to reach their targets. As a natural magnetic nanoparticle (MNP) of biological origin, the magnetosome is a special “organelle” formed by biomineralization in magnetotactic bacteria (MTB) and is essential for MTB magnetic navigation to respond to geomagnetic fields. The magnetic targeting of magnetosomes, however, can be hindered by the aggregation and precipitation of magnetosomes in water and biological fluid environments due to the strong magnetic attraction between particles. In this study, we constructed a magnetosome-like nanoreactor by introducing MTB Mms6 protein into a reverse micelle system. MNPs synthesized by thermal decomposition exhibit the same crystal morphology and magnetism (high saturation magnetization and low coercivity) as natural magnetosomes but have a smaller particle size. The DSPE-mPEG–coated magnetosome-like MNPs exhibit good monodispersion, penetrating the lesion area of a tumor mouse model to achieve magnetic enrichment by an order of magnitude more than in the control groups, demonstrating great prospects for biomedical magnetic targeting applications.
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