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Article: CDK4/6 nano-PROTAC enhances mitochondria-dependent photodynamic therapy and anti-tumor immunity

TitleCDK4/6 nano-PROTAC enhances mitochondria-dependent photodynamic therapy and anti-tumor immunity
Authors
KeywordsCDK4/6
Cell cycle
Immunotherapy
Photodynamic therapy
PROTAC
Issue Date1-Jun-2023
PublisherElsevier
Citation
Nano Today, 2023, v. 50 How to Cite?
Abstract

Cell cycle progression in cancer cells is highly activated, making CDK4/6 inhibition-based cell cycle arrest a potent cancer treatment strategy. To enhance therapeutic efficacy, it is crucial to explore CDK4/6 inhibition-based combination strategies. In this study, we found that combing CDK4/6 PROTAC with Chlorin e6-based photodynamic therapy produced a synergistic anti-cancer effect. This combination effect was mediated by mitochondria accumulation and activation, leading to increased production of reactive oxygen species and apoptosis. To promote clinical translation, we developed a self-assembled, carrier-free nanoparticle system to co-deliver these two molecules. The dual-drug nanoparticles not only induced higher apoptosis but also cooperatively induced immunogenic cell death and chemotaxis of immune cells, remodulating immunosuppressive tumor microenvironment to enhance anti-tumor immunity. This study provides a promising strategy to combine G1 cell cycle blockage and photodynamic therapy and advances the broad applications of PROTAC in clinical cancer treatment.


Persistent Identifierhttp://hdl.handle.net/10722/338830
ISSN
2023 Impact Factor: 13.2
2023 SCImago Journal Rankings: 3.483
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, Tianyi-
dc.contributor.authorZhang, Yaming-
dc.contributor.authorChen, Kang-
dc.contributor.authorHuang, Yi-
dc.contributor.authorLiu, Yuwei-
dc.contributor.authorXu, Shuting-
dc.contributor.authorWang, Weiping-
dc.date.accessioned2024-03-11T10:31:52Z-
dc.date.available2024-03-11T10:31:52Z-
dc.date.issued2023-06-01-
dc.identifier.citationNano Today, 2023, v. 50-
dc.identifier.issn1748-0132-
dc.identifier.urihttp://hdl.handle.net/10722/338830-
dc.description.abstract<p>Cell cycle progression in cancer cells is highly activated, making CDK4/6 inhibition-based cell cycle arrest a potent cancer treatment strategy. To enhance therapeutic efficacy, it is crucial to explore CDK4/6 inhibition-based combination strategies. In this study, we found that combing CDK4/6 <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/protein-catabolism" title="Learn more about PROTAC from ScienceDirect's AI-generated Topic Pages">PROTAC</a> with <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/chlorin" title="Learn more about Chlorin from ScienceDirect's AI-generated Topic Pages">Chlorin</a> e6-based <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/photodynamics" title="Learn more about photodynamic from ScienceDirect's AI-generated Topic Pages">photodynamic</a> therapy produced a synergistic anti-cancer effect. This combination effect was mediated by <a href="https://www.sciencedirect.com/topics/physics-and-astronomy/mitochondria" title="Learn more about mitochondria from ScienceDirect's AI-generated Topic Pages">mitochondria</a> accumulation and activation, leading to increased production of <a href="https://www.sciencedirect.com/topics/chemistry/reactive-oxygen-species" title="Learn more about reactive oxygen species from ScienceDirect's AI-generated Topic Pages">reactive oxygen species</a> and apoptosis. To promote clinical translation, we developed a self-assembled, carrier-free <a href="https://www.sciencedirect.com/topics/chemistry/nanoparticle" title="Learn more about nanoparticle from ScienceDirect's AI-generated Topic Pages">nanoparticle</a> system to co-deliver these two molecules. The dual-drug nanoparticles not only induced higher apoptosis but also cooperatively induced immunogenic cell death and chemotaxis of immune cells, remodulating immunosuppressive tumor <a href="https://www.sciencedirect.com/topics/engineering/microenvironments" title="Learn more about microenvironment from ScienceDirect's AI-generated Topic Pages">microenvironment</a> to enhance anti-tumor immunity. This study provides a promising strategy to combine G1 cell cycle blockage and <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/photodynamics" title="Learn more about photodynamic from ScienceDirect's AI-generated Topic Pages">photodynamic</a> therapy and advances the broad applications of <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/protein-catabolism" title="Learn more about PROTAC from ScienceDirect's AI-generated Topic Pages">PROTAC</a> in clinical cancer treatment.<br></p>-
dc.languageeng-
dc.publisherElsevier-
dc.relation.ispartofNano Today-
dc.subjectCDK4/6-
dc.subjectCell cycle-
dc.subjectImmunotherapy-
dc.subjectPhotodynamic therapy-
dc.subjectPROTAC-
dc.titleCDK4/6 nano-PROTAC enhances mitochondria-dependent photodynamic therapy and anti-tumor immunity-
dc.typeArticle-
dc.identifier.doi10.1016/j.nantod.2023.101890-
dc.identifier.scopuseid_2-s2.0-85161053977-
dc.identifier.volume50-
dc.identifier.eissn1878-044X-
dc.identifier.isiWOS:001019582000001-
dc.identifier.issnl1748-0132-

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