Theranostics 2018; 8(1):92-108. doi:10.7150/thno.21074

Research Paper

Tumor-penetrating Peptide Conjugated and Doxorubicin Loaded T1-T2 Dual Mode MRI Contrast Agents Nanoparticles for Tumor Theranostics

Lipeng Gao1, Jing Yu1, Yang Liu1, Jinge Zhou1, Lei Sun1, Jing Wang1, Jianzhong Zhu1, Hui Peng2, Weiyue Lu3, Lei Yu1, Zhiqiang Yan1✉, Yiting Wang1✉

1. Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
2. Key Laboratory of Polar Materials and Devices, Ministry of Education, School of Information Science and Technology, East China Normal University, Shanghai 200241, China.
3. Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai 201203, China.


The conventional chemotherapeutics could not be traced in vivo and provide timely feedback on the clinical effectiveness of drugs.

Methods: In this study, a tumor-penetrating peptide RGERPPR (RGE) modified, Gd-DTPA conjugated, and doxorubicin (DOX) loaded Fe3O4@SiO2@mSiO2 nanoparticle drug delivery system (Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs) was prepared for tumor theranostics.

Results: The Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs showed a z-average hydrodynamic diameter of about 90 nm, and a pH-sensitive DOX release profile. The 3 T MRI results confirmed the relaxivity of the NPs (r1 = 6.13 mM-1S-1, r2 = 36.89 mM-1S-1). The in vitro cellular uptake and cytotoxicity assays on U87MG cells confirmed that the conjugation of RGERPPR played a significant role in increasing the cellular uptake and cytotoxicity of the NPs. The near-infrared fluorescence in vivo imaging results showed that the NPs could be significantly accumulated in the U87MG tumor tissue, which should result from the mediation of the tumor-penetrating peptide RGERPPR. The MRI results showed that the NPs offered a T1-T2 dual mode contrast imaging effect which would lead to a more precise diagnosis. Compared with unmodified NPs, the RGE-modified NPs showed significantly enhanced MR imaging signal in tumor tissue and antitumor effect, which should also be attributed to the tumor penetrating ability of RGERPPR peptide. Furthermore, the Hematoxylin and Eosin (H&E) staining and TUNEL assay proved that the NPs produced obvious cell apoptosis in tumor tissue.

Conclusions: These results indicated that Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs are an effective targeted delivery system for tumor theranostics, and should have a potential value in the personalized treatment of tumor.

Keywords: Theranostics, Tumor penetrating peptide, T1-T2 dual mode MRI, pH-sensitive release, Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs

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How to cite this article:
Gao L, Yu J, Liu Y, Zhou J, Sun L, Wang J, Zhu J, Peng H, Lu W, Yu L, Yan Z, Wang Y. Tumor-penetrating Peptide Conjugated and Doxorubicin Loaded T1-T2 Dual Mode MRI Contrast Agents Nanoparticles for Tumor Theranostics. Theranostics 2018; 8(1):92-108. doi:10.7150/thno.21074. Available from