Research Papers:

Secondary nuclear targeting of mesoporous silica nano-particles for cancer-specific drug delivery based on charge inversion

Jianwen Zhao, Fengfeng Zhao, Xiyong Wang, Xiaobo Fan and Guoqiu Wu _

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Oncotarget. 2016; 7:70100-70112. https://doi.org/10.18632/oncotarget.12149

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Jianwen Zhao1,2,*, Fengfeng Zhao2,*, Xiyong Wang2, Xiaobo Fan2, Guoqiu Wu1,2

1Center of Clinical Laboratory Medicine of Zhongda Hospital, Southeast University, Nanjing, 210009, China

2Medical School, Southeast University, Nanjing, 210009, China

*These authors contributed equally to this work

Correspondence to:

Xiaobo Fan, email: [email protected]

Guoqiu Wu, email: [email protected]

Keywords: peptide charge inversion, secondary nuclear targeting, mesoporous silica, cancer, delivery

Received: April 28, 2016     Accepted: September 14, 2016     Published: September 20, 2016


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.

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