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

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 Yan^1✉, Yiting Wang^1✉

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.

✉ Corresponding author: zqyanecnu.edu.cn, ytwangecnu.edu.cn

Abstract

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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