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Research Article

pH-activatable lactam-stapled peptide-based nanoassemblies for enhanced chemo-photothermal therapy

Yao Xiao1, Ling Zhang1, Mengzhen Shi2, Rui Tang2, Zherui Jiang2, Yue Song2, Yuan Tian2( ), Shaobing Zhou1( )
Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
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Graphical Abstract

We demonstrate a novel approach for enhancing the therapeutic efficacy of chemo-photothermal therapy by taking advantage of the robust cell permeability and therapeutic effects of stapled peptides. The lactam-stapled proapoptotic peptide could be efficiently activated in acidic tumor microenvironment, thereby promoting the drug delivery to the tumor cells and specific targeting mitochondria, which works in synergy with the doxorubicin (DOX) and local hyperthermia upon near infrared ray (NIR) light irradiation.

Abstract

The practical application of nanomedicines for cancer therapy is generally hampered by their compromised tumor accumulation and transmembrane potency. Cell penetrating peptides (CPPs) have been widely used to enhance the drug delivery efficiency in tumor cells. However, conventional CPPs are vulnerable towards proteases and are generally lack of therapeutic effects. To maximize the efficacy of nanomedicines, new classes of cell penetrating therapeutic modalities are highly desirable. Stapled peptides have drawn wide attention as one of the cell-permeable peptidomimetics for intracellular targets. Herein, we reported a novel approach for enhancing the therapeutic efficacy of chemo-photothermal therapy by taking advantage of the robust cell permeability and therapeutic effects of stapled peptides. The designed pH-activatable lactam-stapled peptide-polymer conjugate formed supramolecular nanoassemblies to encapsulate the chemodrug doxorubicin (DOX). Once reaching the tumor site, the lactam-stapled proapoptotic peptide could be efficiently activated under acidic tumor microenvironment, thereby promoting the drug delivery to the tumor cells and specific targeting mitochondria to interfere with the energy metabolism of tumor cells, which works in synergy with the DOX and local hyperthermia upon near infrared ray (NIR) light irradiation. This work may benefit future design of stapled peptides-based stimuli-responsive nanoplatforms for enhanced cancer therapy.

Keywords

lactam-stapled peptidepH-responsivenanoassemblieschemotherapyphotothermal therapy

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Nano Research
Volume 15 Issue 9,
September 2022
Pages 8315-8325
DOI: 10.1007/s12274-022-4503-3
Cite this article:
Xiao Y, Zhang L, Shi M, et al. pH-activatable lactam-stapled peptide-based nanoassemblies for enhanced chemo-photothermal therapy. Nano Research, 2022, 15(9): 8315-8325. https://doi.org/10.1007/s12274-022-4503-3
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Received: 22 February 2022
Revised: 01 May 2022
Accepted: 04 May 2022
Published: 29 June 2022
© Tsinghua University Press 2022
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