Xu Shuai, Yin Baoru, Guo Jia, Wang Changchun
State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, and Laboratory of Advanced Materials, Fudan University, Shanghai 200433, China.
J Mater Chem B. 2013 Sep 7;1(33):4079-4087. doi: 10.1039/c3tb20238k. Epub 2013 Jul 3.
Uniform hollow magnetic supraparticles (HMSPs) consisting of nanocrystal aggregates in shells are designed and fabricated via a one-pot microwave irradiation process within 10 min, employing casein, a major milk protein, as a structure-directing agent responsible for the formation of hollow structures. The casein micelle (CM)-mediated self-assembled HMSPs exhibit structural uniformity, excellent aqueous dispersibility, enhanced biocompatibility, as well as a high saturation magnetization (∼70 emu g). Herein, CMs serve as soft templates to induce inner hollow cavities through electrostatic interactions between negative CM "brushes" and positive Fe(iii) species, and subsequent degradation of the inner cores under microwave irradiation, meanwhile improving the colloidal stability and biocompatibility of the HMSPs. Besides, the interior cavity size of the HMSPs could be readily tuned in the range of 40 nm to 150 nm, simply by varying the feeding dosage of casein. In light of the interior void and desirable physicochemical properties, the role of HMSPs serving as vehicles for the controlled delivery of DOX into cancer cells has been investigated. Drug release profiles are shown to be pH-responsive with up to 83% DOX release in acidic environments (pH 4.0 and 5.0), whereas low DOX (18%) release occurs at neutral pH (pH 7.4) within 48 h, indicating minimal premature drug release. Moreover, intracellular tracking experiments reveal that DOX-loaded HMSPs could efficiently be taken up by KB cells and exhibit potent anti-proliferation and inhibitory effects against KB cells, as compared to free DOX. Importantly, the DOX-loaded HMSPs show limited cytotoxicity against normal HEK 293 cells with 70% retained viability after incubation at a high concentration of 5.0 μg mL, which further demonstrated the potential of microwave-driven HMSPs as desirable drug delivery vehicles.
通过一锅法微波辐照工艺，在10分钟内设计并制备了由壳层中的纳米晶体聚集体组成的均匀空心磁性超粒子（HMSP），采用酪蛋白（一种主要的乳蛋白）作为负责形成空心结构的结构导向剂。酪蛋白胶束（CM）介导的自组装HMSP表现出结构均匀性、优异的水分散性、增强的生物相容性以及高饱和磁化强度（约70 emu g）。在此，CM作为软模板，通过负性CM“刷”与正性Fe(III)物种之间的静电相互作用诱导内部空心腔，并在微波辐照下使内核随后降解，同时提高了HMSP的胶体稳定性和生物相容性。此外，只需改变酪蛋白的投料量，HMSP的内部腔尺寸就可以在40 nm至150 nm范围内轻松调节。鉴于内部空隙和理想的物理化学性质，研究了HMSP作为将阿霉素（DOX）可控递送至癌细胞的载体的作用。药物释放曲线显示出pH响应性，在酸性环境（pH 4.0和5.0）中DOX释放率高达83%，而在中性pH（pH 7.4）下48小时内DOX释放率较低（18%），表明药物过早释放极少。此外，细胞内追踪实验表明，与游离DOX相比，负载DOX的HMSP可以被KB细胞有效摄取，并对KB细胞表现出强大的抗增殖和抑制作用。重要的是，负载DOX的HMSP对正常HEK 293细胞的细胞毒性有限，在5.0 μg mL的高浓度孵育后仍有70%的细胞活力保留，这进一步证明了微波驱动的HMSP作为理想药物递送载体的潜力。
