Bioorthogonal nanozymes for breast cancer imaging and therapy

• Published in: Journal of controlled release Vol. 357; pp. 31 - 39
• Main Authors: Zhang, Xianzhi, Liu, Yuanchang, Doungchawee, Jeerapat, Castellanos-García, Laura J., Sikora, Kristen N., Jeon, Taewon, Goswami, Ritabrita, Fedeli, Stefano, Gupta, Aarohi, Huang, Rui, Hirschbiegel, Cristina-Maria, Cao-Milán, Roberto, Majhi, Prabin K.D., Cicek, Yagiz Anil, Liu, Liang, Jerry, D. Joseph, Vachet, Richard W., Rotello, Vincent M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-05-2023
• Subjects: Anticancer therapy; Bioorthogonal catalysis; Bioorthogonal nanozymes; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - drug therapy; Catalysis; Cell Membrane; Diagnostic Imaging; Female; Humans; LA-ICP-MS imaging; Nanocatalysts; Nanostructures; Pro-fluorophore activation; Prodrug activation; Nanocatalysts; LA-ICP-MS imaging; Bioorthogonal catalysis; Prodrug activation; Bioorthogonal nanozymes; Pro-fluorophore activation; Anticancer therapy
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2023.03.032

Bioorthogonal catalysis via transition metal catalysts (TMCs) enables the generation of therapeutics locally through chemical reactions not accessible by biological systems. This localization can enhance the efficacy of anticancer treatment while minimizing off-target effects. The encapsulation of TMCs into nanomaterials generates “nanozymes” to activate imaging and therapeutic agents. Here, we report the use of cationic bioorthogonal nanozymes to create localized “drug factories” for cancer therapy in vivo. These nanozymes remained present at the tumor site at least seven days after a single injection due to the interactions between cationic surface ligands and negatively charged cell membranes and tissue components. The prodrug was then administered systemically, and the nanozymes continuously converted the non-toxic molecules into active drugs locally. This strategy substantially reduced the tumor growth in an aggressive breast cancer model, with significantly reduced liver damage compared to traditional chemotherapy.
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•Sustained release of chemotherapeutics at tumor sites using nanomaterials enhances drug efficacy and reduces side effects.•Bioorthogonal nanozymes offer “drug factories” which generate therapeutics in situ using reactions unattainable by biology.•Surface-engineered cationic nanozymes adhere to tissue over ten days in vivo.•Bioorthogonal nanozymes activate anticancer drugs from the prodrug, inhibiting tumor growth with negligible side effects.