Mobile Magnetic Nanocatalysts for Bioorthogonal Targeted Cancer Therapy

• Published in: Advanced functional materials Vol. 28; no. 25
• Main Authors: Hoop, Marcus, Ribeiro, Ana Sofia, Rösch, Daniel, Weinand, Philipp, Mendes, Nuno, Mushtaq, Fajer, Chen, Xiang‐Zhong, Shen, Yang, Pujante, Carlos Franco, Puigmartí‐Luis, Josep, Paredes, Joana, Nelson, Bradley J., Pêgo, Ana Paula, Pané, Salvador
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 20.06.2018
• Subjects: Activation; bioorthogonal chemistry; Cancer; Cancer therapies; cancer therapy; Catalysis; Cell death; Chemical compounds; Chemotherapy; Drugs; In vitro methods and tests; In vivo methods and tests; Iron; iron–palladium; magnetic actuation; Materials science; Nanowires; Palladium; Reduction; Side effects; Tumors; Uracil; Xenotransplantation
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.201705920

The use of magnetic nanorobots to activate chemotherapeutic prodrugs represents a promising alternative to current chemotherapeutic treatments. Here, a hybrid nanowire (NW) for targeted bioorthogonally driven activation of the latent chemotherapeutic prodrug 5‐fluoro‐1‐propargyl‐uracil (Pro‐5‐FU) in in vitro and in vivo cancer models is proposed. The NWs are composed of magnetic iron (Fe) and palladium (Pd), a known bioorthogonal catalyst. In vitro tests with a cancer cell line showed no significant cytotoxic effect by the NWs. In contrast, NWs combined with Pro‐5‐FU lead to a significant reduction of cell viability, similarly to the one induced by its active chemotherapeutic counterpart 5‐fluorouracil (5‐FU). The reduction in cell viability is attributed to the catalytic activation of Pro‐5‐FU into 5‐FU. To demonstrate their targeted therapeutic abilities, magnetic fields are used to attract the FePd NWs to a predefined area within a cultured cancer cell population, causing a local Pro‐5‐FU activation, and subsequent cell death in this region. As a proof of concept, NWs are injected in cancer tumor xenografts. The intraperitoneal injection of Pro‐5‐FU significantly retards tumour growth without causing significant side effects. This work presents a novel chemotherapeutic approach combining nanorobotics and bioorthogonal activation of prodrugs as an efficient alternative to conventional chemotherapy. Iron–palladium‐based magnetic nanocatalysts are used for bioorthogonally driven targeted cancer therapy. The alloy nanocatalysts exhibit bioorthogonal activity by turning a latent prodrug to an anticancer agent. The therapeutic efficiency is demonstrated both in vitro and in vivo. This study presents a novel cancer therapy approach combining nanotechnology, nanorobotics, and bioorthogonal chemistry as an efficient alternative to conventional chemotherapy approaches.