4.7 Article

Co-delivery of anticancer drugs and cell penetrating peptides for improved cancer therapy

Journal

CHINESE CHEMICAL LETTERS
Volume 32, Issue 4, Pages 1559-1562

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.cclet.2020.10.011

Keywords

Metal-organic frameworks; Lysosome escape; pH-responsiveness; Drug delivery; Poly(ethylene glycol)

Funding

  1. National Natural Science Foundation of China [21872085, 21902088]
  2. Project for Scientific Research Innovation Team of Young Scholar in Colleges and Universities of Shandong Province [2020KJC001]

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The study demonstrated the one-pot synthesis of poly(ethylene glycol) mediated ZIF-8 NPs for the co-delivery of an anticancer drug and a cell-penetrating peptide to improve therapeutic efficacy. These pH-responsive NPs showed stability at neutral pH and released the encapsulated drugs at acidic pH, enhancing their cytotoxicity. This strategy provides a new perspective for the design of drug delivery systems and offers more opportunities for biomedical applications.
Delivery systems based on nanoparticles (NPs) have shown great potential to reduce side effects and improve the therapeutic efficacy. Herein, we report the one-pot synthesis of poly(ethylene glycol) mediated zeolitic imidazolate framework-8 (ZIF-8) NPs for the co-delivery of an anticancer drug (i.e., doxorubicin) and a cell penetrating peptide containing histidine and arginine (i.e., H4R4) to improve the efficacy of therapeutic delivery. The cargo-encapsulated ZIF-8 NPs are pH-responsive, which are stable at neutral pH and degradable at acidic pH to release the encapsulated cargos. The released H4R4 can help for endosome/lysosome escape to enhance the cytotoxicity of the encapsulated drugs. In vivo studies demonstrate that the co-delivery of doxorubicin and H4R4 peptides can efficiently inhibit tumor growth without significant side effects. The reported strategy provides a new perspective on the design of drug delivery systems and brings more opportunities for biomedical applications. ? 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

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