Secondary nuclear targeting of mesoporous silica nano-particles for cancer-specific drug delivery based on charge inversion.
Secondary nuclear targeting of mesoporous silica nano-particles for cancer-specific drug delivery based on charge inversion.
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基于电荷反转的介孔二氧化硅纳米颗粒二次核靶向用于癌症特异性药物递送
DOI：
10.18632/oncotarget.12149
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发表时间：
2016-10-25
期刊：
影响因子：
--
通讯作者：
Wu G
中科院分区：
文献类型：
--
作者：
Zhao J;Zhao F;Wang X;Fan X;Wu G
成功开发了一种基于肽电荷反转的多功能纳米药物传递系统，用于抗癌药物的传递和成像。选择直径约50 nm的介孔二氧化硅纳米颗粒（MSN）作为药物储存库，用HIV-1反激活肽-异硫氰酸荧光素（dat - fitc）和YSA-BHQ1对其表面进行修饰。FITC标记的TAT短肽用于促进核内递送，BHQ1猝灭组标记的YSA肽用于特异性结合肿瘤EphA2膜受体。柠檬酸酐（Citraconic anhy酐，Cit）在中性或弱碱性条件下使TAT肽的电荷反转，使带正电荷的YSA肽通过静电吸引与TAT肽结合。两个肽结合后，FITC荧光被BHQ1的空间途径猝灭。然而，cit -氨基键在酸性气氛中不稳定，因此TAT肽的正电荷被恢复，带正电荷的YSA部分被排斥。去除YSA-BHQ1片段后，FITC荧光恢复，TAT肽引导纳米颗粒进入核仁。该纳米给药系统在生理pH下稳定，在酸性缓冲液中快速释放药物，易于被MCF-7细胞吸收。与同等浓度的游离盐酸阿霉素相比，负载阿霉素分子的改性微球对MCF-7细胞的抑制作用相当。因此，这种纳米药物输送系统是一种很有前途的癌症诊断和治疗方法。
A novel multifunctional nano-drug delivery system based on reversal of peptide charge was successfully developed for anticancer drug delivery and imaging. Mesoporous silica nano-particles (MSN) ~50 nm in diameter were chosen as the drug reservoirs, and their surfaces were modified with HIV-1 transactivator peptide-fluorescein isothiocyanate (TAT-FITC) and YSA-BHQ1. The short TAT peptide labeled with FITC was used to facilitate intranuclear delivery, while the YSA peptide tagged with the BHQ1 quencher group was used to specifically bind to the tumor EphA2 membrane receptor. Citraconic anhydride (Cit) was used to invert the charge of the TAT peptide in neutral or weak alkaline conditions so that the positively charged YSA peptide could combine with the TAT peptide through electrostatic attraction. The FITC fluorescence was quenched by the spatial approach of BHQ1 after the two peptides bound to each other. However, the Cit-amino bond was unstable in the acidic atmosphere, so the positive charge of the TAT peptide was restored and the positively charged YSA moiety was repelled. The FITC fluorescence was recovered after the YSA-BHQ1 moiety was removed, and the TAT peptide led the nano-particles into the nucleolus. This nano-drug delivery system was stable at physiological pH, rapidly released the drug in acidic buffer, and was easily taken up by MCF-7 cells. Compared with free doxorubicin hydrochloride at an equal concentration, this modified MSN loaded with doxorubicin molecules had an equivalent inhibitory effect on MCF-7 cells. This nano-drug delivery system is thus a promising method for simultaneous cancer diagnosis and therapy.