Xu Jiating, Han Wei, Cheng Ziyong, Yang Piaoping, Bi Huiting, Yang Dan, Niu Na, He Fei, Gai Shili, Lin Jun
Key Laboratory of Superlight Materials and Surface Technology , Ministry of Education , College of Materials Science and Chemical Engineering , Harbin Engineering University , Harbin , 150001 , P. R. China . Email:
State Key Laboratory of Rare Earth Resource Utilization , Changchun Institute of Applied Chemistry , Chinese Academy of Sciences , Changchun 130021 , P. R. China . Email:
Chem Sci. 2018 Feb 6;9(12):3233-3247. doi: 10.1039/c7sc05414a. eCollection 2018 Mar 28.
Developing nanotheranostics responsive to tumor microenvironments has attracted tremendous attention for on-demand cancer diagnosis and treatment. Herein, a facile Mn-doping strategy was adopted to transform mesoporous silica coated upconversion nanoparticles (UCNPs) to yolk-like upconversion nanostructures which possess a tumor-responsive biodegradation nature. The huge internal space of the innovated nanocarriers is suitable for doxorubicin (DOX) storage, besides, the Mn-doped shell is sensitive to the intratumoral acidity and reducibility, which enables shell biodegradation and further accelerates the breakage of Si-O-Si bonds within the silica framework. This tumor-responsive shell degradation is beneficial for realizing tumor-specific DOX release. Subsequently, polyoxometalate (POM) nanoclusters that can enhance photothermal conversion in response to the tumor reducibility and acidity were modified on the surface of the silica shell, thereby achieving NIR-enhanced shell degradation and also preventing premature DOX leakage. The as-produced thermal effect of the POM couples with the chemotherapy effect of the released DOX to perform a synergetic chemo-photothermal therapy. Additionally, the shell degradation brings size shrinkage to the nanocarriers, allowing faster nanoparticle diffusion and deeper tumor penetration, which is significant for improving theranostic outcomes. Also, the drastic decline of the red/green (R/G) ratio caused by the DOX release can be used to monitor the DOX release content through a fluorescence resonance energy transfer (FRET) method. The MRI effect caused by Mn release together with the MRI/CT/UCL imaging derived from Gd/Yb/Nd/Er co-doped UCNPs under 808 nm laser excitation endow the nanosystem with multiple imaging capability, thus realizing imaging-guided cancer therapy.
开发对肿瘤微环境有响应的纳米诊疗剂在按需癌症诊断和治疗方面引起了极大关注。在此，采用了一种简便的锰掺杂策略，将介孔二氧化硅包覆的上转换纳米粒子（UCNPs）转变为具有肿瘤响应性生物降解特性的蛋黄状上转换纳米结构。创新型纳米载体的巨大内部空间适合储存阿霉素（DOX），此外，锰掺杂壳对肿瘤内的酸度和还原性敏感，这使得壳能够生物降解，并进一步加速二氧化硅骨架内Si-O-Si键的断裂。这种肿瘤响应性壳降解有利于实现肿瘤特异性DOX释放。随后，将能响应肿瘤还原性和酸度增强光热转换的多金属氧酸盐（POM）纳米团簇修饰在二氧化硅壳表面，从而实现近红外增强的壳降解，同时防止DOX过早泄漏。所产生的POM热效应与释放的DOX的化疗效应相结合，进行协同化疗-光热疗法。此外，壳降解使纳米载体尺寸缩小，使纳米粒子扩散更快、肿瘤穿透更深，这对于提高诊疗效果具有重要意义。而且，DOX释放导致的红/绿（R/G）比值急剧下降可通过荧光共振能量转移（FRET）方法用于监测DOX释放量。锰释放引起的磁共振成像（MRI）效应以及在808 nm激光激发下由钆/镱/钕/铒共掺杂UCNPs产生的MRI/CT/上转换发光（UCL）成像赋予纳米系统多重成像能力，从而实现成像引导的癌症治疗。
