Department of Radiology, Cancer Hospital/Institute & Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China.
Nanoscale. 2015 May 7;7(17):7632-43. doi: 10.1039/c5nr00451a.
The construction of intelligent stimuli-responsive nanosystems can substantially improve the sensitivity/resolution/specificity of diagnostic imaging and enhance the therapeutic efficiency of chemotherapy for cancer treatment. This work reports on a generic construction strategy to achieve a multiple stimuli-responsive theranostic system for cancer simply by optimizing the chemical compositions of inorganic nanoplatforms to avoid the tedious and complicated synthetic procedure for traditional organic or organic/inorganic nanosystems. Based on the "breaking up" nature of manganese oxides and specific features of the carbonaceous framework to interact with aromatic drug molecules, manganese oxide nanoparticles were elaborately integrated into hollow mesoporous carbon nanocapsules by a simple in situ framework redox strategy to realize concurrent pH-sensitive T1-weighted magnetic resonance imaging (MRI) and pH-/HIFU-responsive on-demand drug release. The ultrasensitive disease-triggered MRI performance has been successfully demonstrated by a 52.5-fold increase of longitudinal relaxivity (r1 = 10.5 mM(-1) s(-1)) and on nude mice 4T1 xenograft. The pH- and HIFU-triggered doxorubicin release and enhanced therapeutic outcome against multidrug resistance of cancer cells were systematically confirmed. In particular, the fabricated inorganic composite nanocapsules were found to feature unique biological behaviours, such as antimetastasis effect, extremely low hemolysis against red blood cells and high in vivo histocompatibility. This report on the successful construction of a pure inorganic nanosystem with multiple stimuli-responsivenesses may pave the way to new methods for the development of intelligent nanofamilies for cancer therapy.
智能刺激响应纳米系统的构建可以显著提高诊断成像的灵敏度/分辨率/特异性，并增强癌症治疗的化学疗法的治疗效率。本工作报道了一种通用的构建策略，通过优化无机纳米平台的化学成分来实现一种多功能刺激响应治疗系统，从而避免了传统有机或有机/无机纳米系统繁琐而复杂的合成过程。基于锰氧化物的“分裂”性质和碳骨架与芳香药物分子相互作用的特定特征，通过简单的原位框架氧化还原策略，将氧化锰纳米颗粒精细地整合到中空介孔碳纳米胶囊中，以实现 pH 敏感的 T1 加权磁共振成像 (MRI) 和 pH-/HIFU 响应的按需药物释放。通过在裸鼠 4T1 异种移植模型中纵向弛豫率 (r1 = 10.5 mM(-1) s(-1)) 提高 52.5 倍，成功证明了超灵敏疾病触发 MRI 性能。pH 和 HIFU 触发的阿霉素释放和增强的多药耐药癌细胞治疗效果得到了系统证实。特别是，所制备的无机复合纳米胶囊表现出独特的生物学行为，如抗转移作用、对红细胞的极低溶血和高体内组织相容性。本报告成功构建了具有多重刺激响应性的纯无机纳米系统，为智能纳米家族治疗癌症的发展开辟了新途径。
