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Theranostics 2020; 10(12):5550-5564. doi:10.7150/thno.42633 This issue Cite

Research Paper

Cytochrome P450 enzyme-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between clopidogrel and photosensitizer

Qiu Wang1*, Mengchi Sun1*, Dan Li1, Chang Li1, Cong Luo1, Zhaomeng Wang1, Wenjuan Zhang1, Zimeng Yang1, Yao Feng2, Shuang Wang3, Zhonggui He1, Haotian Zhang4, Qiming Kan4, Wei Sun5✉, Jin Sun1✉

1. Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China
2. Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China
3. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China
4. School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China
5. College of Medical Device, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China
*Both authors contributed equally

✉ Corresponding authors: Prof. Jin Sun Ph.D, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, P. R. China. Tel/Fax: +86-24-23986321; E-mail: sunjinedu.cn Or Dr. Wei Sun, College of Medical Device, Shen More

Citation:
Wang Q, Sun M, Li D, Li C, Luo C, Wang Z, Zhang W, Yang Z, Feng Y, Wang S, He Z, Zhang H, Kan Q, Sun W, Sun J. Cytochrome P450 enzyme-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between clopidogrel and photosensitizer. Theranostics 2020; 10(12):5550-5564. doi:10.7150/thno.42633. https://www.thno.org/v10p5550.htm
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Abstract

Graphic abstract

Reactive oxygen species (ROS)-based photodynamic therapy (PDT) has a widespread application in cancer therapy. Nevertheless, the efficiency of PDT is far from satisfactory. One major impediment is the overexpression of glutathione (GSH) in tumor cells, which could deplete the level of PDT-generated ROS. Herein, we develop a novel type of cytochrome P450 enzyme-mediated auto-enhanced photodynamic co-nanoassembly between clopidogrel (CPG) and photosensitizer pyropheophorbide a (PPa).

Methods: In this work, we prepare the co-assembled nanoparticles of CPG and PPa (CPG/PPa NPs) by using one-step precipitation method. The assembly mechanism, drug release behavior, GSH consumption, ROS generation, cellular uptake, cytotoxicity of CPG/PPa NPs are investigated in vitro. The mice bearing 4T1 tumor are employed to evaluate in vivo biodistribution and anti-tumor effect of CPG/PPa NPs.

Results: Such CPG/PPa NPs could disrupt the intracellular redox homeostasis, resulting from the elimination of GSH by CPG active metabolite mediated by cytochrome P450 enzyme (CYP2C19). The in vivo assays reveal that CPG/PPa NPs not only increase the drug accumulation in tumor sites but also significantly suppress tumor growth in BALB/c mice bearing 4T1 tumor. With CPG-mediated GSH consumption and PPa-triggered ROS generation, CPG/PPa NPs show the enhanced PDT treatment effect by breaking intracellular redox balance.

Conclusion: Our findings provide a valuable knowledge for the rational design of the PDT-based combinational cancer therapy.

Keywords: cytochrome P450 enzyme, glutathione, photodynamic therapy, clopidogrel, disrupt intracellular redox homeostasis

Citation styles

APA
Wang, Q., Sun, M., Li, D., Li, C., Luo, C., Wang, Z., Zhang, W., Yang, Z., Feng, Y., Wang, S., He, Z., Zhang, H., Kan, Q., Sun, W., Sun, J. (2020). Cytochrome P450 enzyme-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between clopidogrel and photosensitizer. Theranostics, 10(12), 5550-5564. https://doi.org/10.7150/thno.42633.

ACS
Wang, Q.; Sun, M.; Li, D.; Li, C.; Luo, C.; Wang, Z.; Zhang, W.; Yang, Z.; Feng, Y.; Wang, S.; He, Z.; Zhang, H.; Kan, Q.; Sun, W.; Sun, J. Cytochrome P450 enzyme-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between clopidogrel and photosensitizer. Theranostics 2020, 10 (12), 5550-5564. DOI: 10.7150/thno.42633.

NLM
Wang Q, Sun M, Li D, Li C, Luo C, Wang Z, Zhang W, Yang Z, Feng Y, Wang S, He Z, Zhang H, Kan Q, Sun W, Sun J. Cytochrome P450 enzyme-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between clopidogrel and photosensitizer. Theranostics 2020; 10(12):5550-5564. doi:10.7150/thno.42633. https://www.thno.org/v10p5550.htm

CSE
Wang Q, Sun M, Li D, Li C, Luo C, Wang Z, Zhang W, Yang Z, Feng Y, Wang S, He Z, Zhang H, Kan Q, Sun W, Sun J. 2020. Cytochrome P450 enzyme-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between clopidogrel and photosensitizer. Theranostics. 10(12):5550-5564.

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