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Self-delivery of a peptide-based prodrug for tumor-targeting therapy

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Abstract

A novel self-delivered prodrug system was fabricated for tumor-targeting therapy. In this nanosystem, the Arg-Gly-Asp-Ser (RGDS) tetrapeptide was used to improve the therapeutic index to integrin-overexpressing tumor cells. The antitumorous drug camptothecin was further appended to the ε-amino group of lysine by 20-O-succinyl linkage and controllably released via hydrolytic cleavage. Prodrug molecules self-assembled into fibrillar nano-architectures and achieved the capability of self-delivery after being injected subcutaneously into mice. Introduction of hydrophobic myristic acid favored the self-assembly and enhanced the cellular internalization of the prodrugs. In vitro and in vivo studies demonstrated that the self-assembled nanofibers could effectively target integrinoverexpressing tumorous cells and inhibit tumor growth via RGD-mediated specific targeting. Therefore, the traditional idea that fibrillar structures hold low therapeutic efficacy due to poor cell uptake can be challenged.

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Authors and Affiliations

  1. Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, China

    Mengyun Peng, Siyong Qin, Huizhen Jia, Diwei Zheng, Lei Rong & Xianzheng Zhang

  2. School of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan, 430074, China

    Siyong Qin

  3. Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials; Key Laboratory for the Green Preparation and Application of Functional Materials of Ministry of Education, Hubei University, Wuhan, 430062, China

    Diwei Zheng

Authors
  1. Mengyun Peng
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  2. Siyong Qin
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  3. Huizhen Jia
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  4. Diwei Zheng
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  6. Xianzheng Zhang
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Correspondence to Xianzheng Zhang.

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These authors contributed equally to this work.

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Peng, M., Qin, S., Jia, H. et al. Self-delivery of a peptide-based prodrug for tumor-targeting therapy. Nano Res. 9, 663–673 (2016). https://doi.org/10.1007/s12274-015-0945-1

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  • DOI: https://doi.org/10.1007/s12274-015-0945-1

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