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- Publisher Website: 10.1016/j.nantod.2023.101890
- Scopus: eid_2-s2.0-85161053977
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Article: CDK4/6 nano-PROTAC enhances mitochondria-dependent photodynamic therapy and anti-tumor immunity
| Title | CDK4/6 nano-PROTAC enhances mitochondria-dependent photodynamic therapy and anti-tumor immunity |
|---|---|
| Authors | |
| Keywords | CDK4/6 Cell cycle Immunotherapy Photodynamic therapy PROTAC |
| Issue Date | 1-Jun-2023 |
| Publisher | Elsevier |
| 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 Identifier | http://hdl.handle.net/10722/338830 |
| ISSN | 2023 Impact Factor: 13.2 2023 SCImago Journal Rankings: 3.483 |
| ISI Accession Number ID |
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Wang, Tianyi | - |
| dc.contributor.author | Zhang, Yaming | - |
| dc.contributor.author | Chen, Kang | - |
| dc.contributor.author | Huang, Yi | - |
| dc.contributor.author | Liu, Yuwei | - |
| dc.contributor.author | Xu, Shuting | - |
| dc.contributor.author | Wang, Weiping | - |
| dc.date.accessioned | 2024-03-11T10:31:52Z | - |
| dc.date.available | 2024-03-11T10:31:52Z | - |
| dc.date.issued | 2023-06-01 | - |
| dc.identifier.citation | Nano Today, 2023, v. 50 | - |
| dc.identifier.issn | 1748-0132 | - |
| dc.identifier.uri | http://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.language | eng | - |
| dc.publisher | Elsevier | - |
| dc.relation.ispartof | Nano Today | - |
| dc.subject | CDK4/6 | - |
| dc.subject | Cell cycle | - |
| dc.subject | Immunotherapy | - |
| dc.subject | Photodynamic therapy | - |
| dc.subject | PROTAC | - |
| dc.title | CDK4/6 nano-PROTAC enhances mitochondria-dependent photodynamic therapy and anti-tumor immunity | - |
| dc.type | Article | - |
| dc.identifier.doi | 10.1016/j.nantod.2023.101890 | - |
| dc.identifier.scopus | eid_2-s2.0-85161053977 | - |
| dc.identifier.volume | 50 | - |
| dc.identifier.eissn | 1878-044X | - |
| dc.identifier.isi | WOS:001019582000001 | - |
| dc.identifier.issnl | 1748-0132 | - |