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Genetically engineered nano‐melittin vesicles for multimodal synergetic cancer therapy

Melittin, the principal constituent in bee venom, is an attractive candidate for cancer therapy. However, its clinical applications are limited by hemolysis, nonspecific cytotoxicity, and rapid metabolism. Herein, a novel genetically engineered vesicular antibody‐melittin (VAM) drug delivery platfor...

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Autores principales: Zhang, Jianzhong, Liu, Xue, Xia, Yutian, Xu, Shuyu, Liu, Xuan, Xiao, Haiqing, Wang, Xiaoyong, Liu, Chao, Liu, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658496/
https://www.ncbi.nlm.nih.gov/pubmed/38023709
http://dx.doi.org/10.1002/btm2.10482
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author Zhang, Jianzhong
Liu, Xue
Xia, Yutian
Xu, Shuyu
Liu, Xuan
Xiao, Haiqing
Wang, Xiaoyong
Liu, Chao
Liu, Gang
author_facet Zhang, Jianzhong
Liu, Xue
Xia, Yutian
Xu, Shuyu
Liu, Xuan
Xiao, Haiqing
Wang, Xiaoyong
Liu, Chao
Liu, Gang
author_sort Zhang, Jianzhong
collection PubMed
description Melittin, the principal constituent in bee venom, is an attractive candidate for cancer therapy. However, its clinical applications are limited by hemolysis, nonspecific cytotoxicity, and rapid metabolism. Herein, a novel genetically engineered vesicular antibody‐melittin (VAM) drug delivery platform was proposed and validated for targeted cancer combination therapy. VAM generated from the cellular plasma membrane was bio‐synthetically fabricated, with the recombinant protein (hGC33 scFv‐melittin) being harbored and displayed on the cell membrane. The bioactive and targetable nanomelittin conjugated by hGC33 scFv could be released in an MMP14‐responsive manner at tumor sites, which reduced off‐target toxicity, especially the hemolytic activity of melittin. Importantly, VAM could be loaded with small‐molecule drugs or nanoparticles for combination therapy. Nanomelittin formed pores in membranes and disturbed phospholipid bilayers, which allowed the anticancer agents (i.e., chemotherapeutic drug doxorubicin and sonosensitizer purpurin 18 nanoparticles) co‐delivered by VAM to penetrate deeper tumor sites, leading to synergistic therapeutic effects. In particular, the punching effect generated by sonodynamic therapy further improved the immunomodulatory effect of nanomelittin to activate the immune response. Taken together, our findings indicate that clinically translatable VAM‐based strategies represent a universal, promising approach to multimodal synergetic cancer therapy.
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spelling pubmed-106584962023-01-04 Genetically engineered nano‐melittin vesicles for multimodal synergetic cancer therapy Zhang, Jianzhong Liu, Xue Xia, Yutian Xu, Shuyu Liu, Xuan Xiao, Haiqing Wang, Xiaoyong Liu, Chao Liu, Gang Bioeng Transl Med Special Issue Articles Melittin, the principal constituent in bee venom, is an attractive candidate for cancer therapy. However, its clinical applications are limited by hemolysis, nonspecific cytotoxicity, and rapid metabolism. Herein, a novel genetically engineered vesicular antibody‐melittin (VAM) drug delivery platform was proposed and validated for targeted cancer combination therapy. VAM generated from the cellular plasma membrane was bio‐synthetically fabricated, with the recombinant protein (hGC33 scFv‐melittin) being harbored and displayed on the cell membrane. The bioactive and targetable nanomelittin conjugated by hGC33 scFv could be released in an MMP14‐responsive manner at tumor sites, which reduced off‐target toxicity, especially the hemolytic activity of melittin. Importantly, VAM could be loaded with small‐molecule drugs or nanoparticles for combination therapy. Nanomelittin formed pores in membranes and disturbed phospholipid bilayers, which allowed the anticancer agents (i.e., chemotherapeutic drug doxorubicin and sonosensitizer purpurin 18 nanoparticles) co‐delivered by VAM to penetrate deeper tumor sites, leading to synergistic therapeutic effects. In particular, the punching effect generated by sonodynamic therapy further improved the immunomodulatory effect of nanomelittin to activate the immune response. Taken together, our findings indicate that clinically translatable VAM‐based strategies represent a universal, promising approach to multimodal synergetic cancer therapy. John Wiley & Sons, Inc. 2023-01-04 /pmc/articles/PMC10658496/ /pubmed/38023709 http://dx.doi.org/10.1002/btm2.10482 Text en © 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Special Issue Articles
Zhang, Jianzhong
Liu, Xue
Xia, Yutian
Xu, Shuyu
Liu, Xuan
Xiao, Haiqing
Wang, Xiaoyong
Liu, Chao
Liu, Gang
Genetically engineered nano‐melittin vesicles for multimodal synergetic cancer therapy
title Genetically engineered nano‐melittin vesicles for multimodal synergetic cancer therapy
title_full Genetically engineered nano‐melittin vesicles for multimodal synergetic cancer therapy
title_fullStr Genetically engineered nano‐melittin vesicles for multimodal synergetic cancer therapy
title_full_unstemmed Genetically engineered nano‐melittin vesicles for multimodal synergetic cancer therapy
title_short Genetically engineered nano‐melittin vesicles for multimodal synergetic cancer therapy
title_sort genetically engineered nano‐melittin vesicles for multimodal synergetic cancer therapy
topic Special Issue Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658496/
https://www.ncbi.nlm.nih.gov/pubmed/38023709
http://dx.doi.org/10.1002/btm2.10482
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