Stimuli-Responsive "Cluster Bomb" for Programmed Tumor Therapy
Stimuli-Responsive "Cluster Bomb" for Programmed Tumor Therapy
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用于程序化肿瘤治疗的刺激响应“集束炸弹”
DOI：
10.1021/acsnano.7b03088
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发表时间：
2017-07-01
期刊：
影响因子：
17.1
通讯作者：
Zhang, Xian-Zheng
中科院分区：
文献类型：
--
作者：
Lei, Qi;Wang, Shi-Bo;Zhang, Xian-Zheng
在本文中，设计了一种负载阿霉素（DOX）并用肿瘤归巢/穿透肽tLyP - 1修饰的二硫化钨量子点（WS₂ - HP）封端的介孔二氧化硅纳米粒子（MSN），并将其作为一种刺激响应的“集束炸弹”用于高效肿瘤抑制。表面的tLyP - 1肽既能促进DOX@MSN - WS₂ - HP归巢到4T1肿瘤，又能极大地增强WS₂ - HP在肿瘤中的穿透能力。作为“子炸弹”和“分配器”之间连接物的苯甲亚胺键在正常物理条件下稳定，在pH 6.8时相当不稳定。到达弱酸性肿瘤微环境后，该纳米平台可迅速分解为两部分：（1）带正电的DOX@MSN - NH₂，用于对表面肿瘤细胞进行高效化疗；（2）具有增强的肿瘤穿透能力的小尺寸WS₂ - HP，用于对深部肿瘤细胞进行近红外（NIR）光触发的光热治疗（PTT）。DOX@MSN - WS₂ - HP在杀死不同深度的肿瘤细胞后，表现出显著的抗肿瘤效果，这在临床试验中将具有巨大潜力。
In this paper, mesoporous silica nanoparticle (MSN) loaded with doxorubicin (DOX) and capped with tumor-homing/-penetrating peptide tLyP-1-modified tungsten disulfide quantum dots (WS2-HP) was designed and applied as a stimuli-responsive "Cluster Bomb" for high-performance tumor suppression. The peptide tLyP-1 on the surface can both facilitate the homing of DOX@MSN-WS2-HP to 4T1 tumor and greatly enhance the penetration of WS2-HP in tumor. The benzoic imine bonds as the linkers between "bomblets" and "dispenser" are stable under normal physical conditions and quite labile at pH 6.8. After arriving at the mild acidic tumor microenvironment, the nanoplatform can rapidly break into two parts: (1) electropositive DOX@MSN-NH2 for efficient chemotherapy on surface tumor cells and (2) small-sized WS2-HP with improved tumor penetrating ability for near-infrared (NIR)-light-triggered photothermal therapy (PTT) among deep-seated tumor cells. Having killed the tumor cells in different depths, DOX@MSN-WS2-HP exhibited significant antitumor effect, which will find great potential in clinical trials.