State Laboratory of High Performance Ceramic and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, PR China.
Biomaterials. 2012 Oct;33(29):7126-37. doi: 10.1016/j.biomaterials.2012.06.059. Epub 2012 Jul 11.
Nano-biotechnology has been introduced into cancer theranostics by engineering a new generation of highly versatile hybrid mesoporous composite nanocapsules (HMCNs) for manganese-based pH-responsive dynamic T(1)-weighted magnetic resonance imaging (MRI) to efficiently respond and detect the tumor acidic microenvironment, which was further integrated with ultrasonographic function based on the intrinsic unique hollow nanostructures of HMCNs for potentially in vitro and in vivo dual-modality cancer imaging. The manganese oxide-based multifunctionalization of hollow mesoporous silica nanoparticles was achieved by an in situ redox reaction using mesopores as the nanoreactors. Due to the dissolution nature of manganese oxide nanoparticles under weak acidic conditions, the relaxation rate r(1) of manganese-based mesoporous MRI-T(1) contrast agents (CAs) could reach 8.81 mM(-1)s(-1), which is a 11-fold magnitude increase compared to the neutral condition, and is almost two times higher than commercial Gd(III)-based complex agents. This is also the highest r(1) value ever reported for manganese oxide nanoparticles-based MRI-T(1) CAs. In addition, the hollow interiors and thin mesoporous silica shells endow HMCNs with the functions of CAs for efficient in vitro and in vivo ultrasonography under both harmonic- and B-modes. Importantly, the well-defined mesopores and large hollow interiors of HMCNs could encapsulate and deliver anticancer agents (doxorubicin) intracellularly to circumvent the multidrug resistance (MDR) of cancer cells and restore the anti-proliferative effect of drugs by nanoparticle-mediated endocytosis process, intracellular drug release and P-gp inhibition/ATP depletion in cancer cells.
纳米生物技术已经被引入癌症治疗学中，通过工程设计新一代多功能杂化介孔复合纳米胶囊（HMCNs），用于基于锰的 pH 响应动态 T1 加权磁共振成像（MRI），以有效响应和检测肿瘤酸性微环境，这进一步集成了超声功能，基于 HMCNs 的固有独特的空心纳米结构，用于潜在的体外和体内双模态癌症成像。中空介孔硅纳米粒子的基于氧化锰的多功能化是通过原位氧化还原反应利用介孔作为纳米反应器来实现的。由于氧化锰纳米粒子在弱酸性条件下的溶解性质，基于锰的介孔 MRI-T1 对比剂（CAs）的弛豫率 r1 可以达到 8.81 mM-1s-1，与中性条件相比增加了 11 倍，几乎是商业 Gd（III）基复合物的两倍。这也是迄今为止报道的基于氧化锰纳米粒子的 MRI-T1 CAs 的最高 r1 值。此外，空心内部和薄的介孔硅壳使 HMCNs 具有高效的体外和体内超声功能，适用于谐波和 B 模式。重要的是，HMCNs 的明确介孔和大的空心内部可以将抗癌药物（阿霉素）包封并递送到细胞内，以规避癌细胞的多药耐药性（MDR），并通过纳米颗粒介导的内吞作用、细胞内药物释放和 P-gp 抑制/ATP 耗竭来恢复药物的抗增殖作用。
