pH-activatable lactam-stapled peptide-based nanoassemblies for enhanced chemo-photothermal therapy
),
Shaobing Zhou1(
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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.
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pH-activatable lactam-stapled peptide-based nanoassemblies for enhanced chemo-photothermal therapy
), Shaobing Zhou1(
)
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.
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Acknowledgements
This work was supported by the National Key Research and Development (R&D) Program of China (No. 2021YFB3800900), the Natural Science Foundation of China (Nos. 51725303, 21708031, and 52033007), the National Postdoctoral Program for Innovative Talents (No. BX20180264), China Postdoctoral Science Foundation (No. 2018M643519), the Sichuan Science and Technology Program (No. 2020JDRC0051), and the Fundamental Research Funds for the Central Universities (No. 2682021ZTPY075). The authors thank the Analysis and Testing Center of Southwest Jiaotong University. All animal procedures were carried out according to the Institutional Animal Care and Use Committee of Southwest Jiaotong University.
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