In Situ Prodrug Activation by an Affibody-Ruthenium Catalyst Hybrid for HER2-Targeted Chemotherapy
Zhennan Zhao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorXuan Tao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorYanxuan Xie
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorQi Lai
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorWenkai Lin
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorKai Lu
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorJinhui Wang
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Wei Xia
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Zong-Wan Mao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorZhennan Zhao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorXuan Tao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorYanxuan Xie
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorQi Lai
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorWenkai Lin
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorKai Lu
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorJinhui Wang
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Wei Xia
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Zong-Wan Mao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorAbstract
Transition-metal catalysts exhibit great potential as therapeutic agents to inhibit tumor growth. However, the precise delivery and in situ catalysis are challenging in catalytic medicine. Herein, we report an anti-HER2 affibody-ruthenium catalyst hybrid, named Ru-HER2 for selective and effective killing of cancer cells. Ru-HER2 binds to the HER2 receptor on a tumor cell and in situ catalyzes the activation of gemcitabine prodrug, resulting in enhanced selectivity in suppression of tumor growth and reduction of side effects. Immunoblotting reveals that Ru-HER2 in combination with gemcitabine prodrug can not only induce DNA damage, but also effectively block the HER2 signaling pathway in cancer cells. Therefore, the HER2-targeted chemotherapy exhibits substantially high anticancer activity toward HER2-positive cancer cells in vitro and in vivo. In a word, we report the first affibody-ruthenium catalyst hybrid and reveal its potential for effective HER2-targeted cancer chemotherapy.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
| Filename | Description |
|---|---|
| ange202202855-sup-0001-misc_information.pdf1.8 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1T. Völker, F. Dempwolff, P. L. Graumann, E. Meggers, Angew. Chem. Int. Ed. 2014, 53, 10536–10540; Angew. Chem. 2014, 126, 10705–10710.
- 2J. P. C. Coverdale, I. Romero-Canelon, C. Sanchez-Cano, G. J. Clarkson, A. Habtemariam, M. Wills, P. J. Sadler, Nat. Chem. 2018, 10, 347–354.
- 3H. Y. Huang, S. Banerjee, K. Q. Qiu, P. Y. Zhang, O. Blacque, T. Malcomson, M. J. Paterson, G. J. Clarkson, M. Staniforth, V. G. Stavros, G. Gasser, H. Chao, P. J. Sadler, Nat. Chem. 2019, 11, 1041–1048.
- 4C. Zhang, D. L. Ni, Y. Y. Liu, H. L. Yao, W. B. Bu, J. L. Shi, Nat. Nanotechnol. 2017, 12, 378–386.
- 5J. J. Soldevila-Barreda, N. Metzler-Nolte, Chem. Rev. 2019, 119, 829–869.
- 6Z. Yu, J. A. Cowan, Chem. Eur. J. 2017, 23, 14113–14127.
- 7F. M. Wang, Y. Zhang, Z. Du, J. S. Ren, X. G. Qu, Nat. Commun. 2018, 9, 1209.
- 8F. M. Wang, Y. Zhang, Z. W. Liu, Z. Du, L. Zhang, J. S. Ren, X. G. Qu, Angew. Chem. Int. Ed. 2019, 58, 6987–6992; Angew. Chem. 2019, 131, 7061–7066.
- 9D. W. Shen, L. M. Pouliot, M. D. Hall, M. M. Gottesman, Pharmacol. Rev. 2012, 64, 706–721.
- 10A. S. Abu-Surrah, M. Kettunen, Curr. Med. Chem. 2006, 13, 1337–1357.
- 11J. Clavadetscher, E. Indrigo, S. V. Chankeshwara, A. Lilienkampf, M. Bradley, Angew. Chem. Int. Ed. 2017, 56, 6864–6868; Angew. Chem. 2017, 129, 6968–6972.
- 12Y. L. Liu, S. Pujals, P. J. M. Stals, T. Paulohrl, S. I. Presolski, E. W. Meijer, L. Albertazzi, A. R. A. Palmans, J. Am. Chem. Soc. 2018, 140, 3423–3433.
- 13A. Beck, L. Goetsch, C. Dumontet, N. Corvaïa, Nat. Rev. Drug Discovery 2017, 16, 315–337.
- 14V. del Solar, M. Contel, J. Inorg. Biochem. 2019, 199, 110780.
- 15N. Curado, G. Dewaele-Le Roi, S. Poty, J. S. Lewis, M. Contel, Chem. Commun. 2019, 55, 1394–1397.
- 16M. J. Matos, C. Labão-Almeida, C. Sayers, O. Dada, M. Tacke, G. J. L. Bernardes, Chem. Eur. J. 2018, 24, 12250–12253.
- 17J. D. Bargh, A. Isidro-Llobet, J. S. Parker, D. R. Spring, Chem. Soc. Rev. 2019, 48, 4361–4374.
- 18D. Zhang, P. S. Dragovich, S. F. Yu, Y. Ma, T. H. Pillow, J. D. Sadowsky, D. Su, W. Wang, A. Polson, S. C. Khojasteh, C. Hop, Drug Metab. Dispos. 2019, 47, 1146–1155.
- 19B. J. Stenton, B. L. Oliveira, M. J. Matos, L. Sinatra, G. J. L. Bernardes, Chem. Sci. 2018, 9, 4185–4189.
- 20R. Rossin, R. M. Versteegen, J. Wu, A. Khasanov, H. J. Wessels, E. J. Steenbergen, W. Ten Hoeve, H. M. Janssen, A. van Onzen, P. J. Hudson, M. S. Robillard, Nat. Commun. 2018, 9, 1484.
- 21F. Lin, L. Chen, H. Zhang, W. S. Ching Ngai, X. Zeng, J. Lin, P. R. Chen, CCS Chem. 2019, 1, 226.
- 22C. A. Hudis, N. Engl. J. Med. 2007, 357, 39–51.
- 23Y. Zhang, Q. Ni, C. Xu, B. Wan, Y. Geng, G. Zheng, Z. Yang, J. Tao, Y. Zhao, J. Wen, J. Zhang, S. Wang, Y. Tang, Y. Li, Q. Zhang, L. Liu, Z. Teng, G. Lu, ACS Appl. Mater. Interfaces 2019, 11, 3654–3665.
- 24J. T. Weiss, J. C. Dawson, C. Fraser, W. Rybski, C. Torres-Sánchez, M. Bradley, E. E. Patton, N. O. Carragher, A. Unciti-Broceta, J. Med. Chem. 2014, 57, 5395–5404.
- 25B. C. Kuenen, L. Rosen, E. F. Smit, M. R. Parson, M. Levi, R. Ruijter, H. Huisman, M. A. Kedde, P. Noordhuis, W. J. van der Vijgh, G. J. Peters, G. F. Cropp, P. Scigalla, K. Hoekman, H. M. Pinedo, G. Giaccone, J. Clin. Oncol. 2002, 20, 1657–1667.
- 26B. Law in Handbook of Analytical Separations, Vol. 114 (Ed.: I. D. Wilson), Elsevier Science, Amsterdam, 2003, pp. 271–292.
- 27E. Molnár in Glutamate Receptors: Methods and Protocols (Eds.: C. Burger, M. J. Velardo), Springer, New York, 2019, pp. 47–54.
- 28Z. Mitri, T. Constantine, R. O'Regan, Chemother. Res. Pract. 2012, 2012, 743193.
- 29M. Brandão, N. F. Pondé, F. Poggio, N. Kotecki, M. Salis, M. Lambertini, E. de Azambuja, Expert Rev. Anticancer Ther. 2018, 18, 629–649.
- 30B. Ewald, D. Sampath, W. Plunkett, Mol. Cancer Ther. 2007, 6, 1239–1248.
- 31H. Kawaguchi, Y. Terai, A. Tanabe, H. Sasaki, M. Takai, S. Fujiwara, K. Ashihara, Y. Tanaka, T. Tanaka, S. Tsunetoh, M. Kanemura, M. Ohmichi, J. Ovarian Res. 2014, 7, 38.
- 32Y. Yarden, Eur. J. Cancer 2001, 37 Suppl 4, S3–S8.
- 33M. Pickl, C. H. Ries, Oncogene 2009, 28, 461–468.
- 34A. Ivascu, M. Kubbies, J. Biomol. Screening 2006, 11, 922–932.
- 35D. W. Jung, E. S. Oh, S. H. Park, Y. T. Chang, C. H. Kim, S. Y. Choi, D. R. Williams, Mol. BioSyst. 2012, 8, 1930–1939.
- 36S. W. Jin, D. Beis, T. Mitchell, J. N. Chen, D. Y. Stainier, Development 2005, 132, 5199–5209.
Citing Literature
This is the
German version
of Angewandte Chemie.
Note for articles published since 1962:
Do not cite this version alone.
Take me to the International Edition version with citable page numbers, DOI, and citation export.
We apologize for the inconvenience.
