The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
A Photocaged, Water-Oxidizing, and Nucleolus-Targeted Pt(IV) Complex with a Distinct Anticancer Mechanism
Abstract
Targeted anticancer prodrugs that can be controllably activated are highly desired for personalized precision medicine in cancer therapy. Such prodrugs with unique action modes are also promising to overcome drug resistance. Herein, we report coumaplatin, an oxaliplatin-based and photocaged Pt(IV) prodrug, to realize nuclear accumulation along with "on-demand" activation. This prodrug is based on a Pt(IV) complex that can be efficiently photoactivated via water oxidation without the requirement of a reducing agent. Coumaplatin accumulates very efficiently in the nucleoli, and upon photoactivation, this prodrug exhibits a level of photocytotoxicity up to 2 orders of magnitude higher than that of oxaliplatin. Unexpectedly, this prodrug presents strikingly enhanced tumor penetration ability and utilizes a distinct action mode to overcome drug resistance; i.e., coumaplatin but not oxaliplatin induces cell senescence, p53-independent cell death, and immunogenic cell death along with T cell activation. Our findings not only provide a novel strategy for the rational design of controllably activated and nucleolus-targeted Pt(IV) anticancer prodrugs but also demonstrate that accumulating conventional platinum drugs to the nucleus is a practical way to change its canonical mechanism of action and to achieve reduced resistance.
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Cellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473
Baar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., Stryeck, S., Rijksen, Y., van Willigenburg, H., Feijtel, D. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.031 · Cited by 1,454
Hall, B. M., Balan, V., Gleiberman, A. S., Strom, E., Krasnov, P., Virtuoso, L. P., Rydkina, E., Vujcic, S., Balan, K., Gitlin, I. I., et al. (2017) · Aging · doi:10.18632/aging.101268 · Cited by 407
Cellular senescence: Immunosurveillance and future immunotherapy
Burton, D. G. A., & Stolzing, A. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.02.001 · Cited by 221
Cellular senescence impact on immune cell fate and function
Vicente, R., Mausset-Bonnefont, A.-L., Jorgensen, C., Louis-Plence, P., & Brondello, J.-M. (2016) · Aging Cell · doi:10.1111/acel.12455 · Cited by 151
Cited by
Stimuli-Responsive Polymer-Based Nanosystems for Cancer Theranostics
Wei, D., Sun, Y., Zhu, H., & Fu, Q. (2023) · ACS Nano · doi:10.1021/acsnano.3c06019 · Cited by 303
Metal-based anticancer agents as immunogenic cell death inducers: the past, present, and future
Sen, S., Won, M., Levine, M. S., Noh, Y., Sedgwick, A. C., Kim, J. S., Sessler, J. L., & Arambula, J. F. (2022) · Chemical Society Reviews · doi:10.1039/d1cs00417d · Cited by 297
Metadata
- Authors
- Deng, Z., Wang, N., Liu, Y., Xu, Z., Wang, Z., Lau, T.-C., & Zhu, G.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-03-27
- Volume
- 142
- Issue
- 17
- Pages
- 7803-7812
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W3013235937
- Cited by
- 239
- References
- 6
- FWCI
- 10.99
- Type
- journal article
- Language
- en
- Open access
- closed
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- Deng, Z., Wang, N., Liu, Y., Xu, Z., Wang, Z., Lau, T.-C., & Zhu, G. (2020). A Photocaged, Water-Oxidizing, and Nucleolus-Targeted Pt(IV) Complex with a Distinct Anticancer Mechanism. Journal of the American Chemical Society. https://doi.org/10.1021/jacs.0c00221
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