期刊
ADVANCED FUNCTIONAL MATERIALS
卷 28, 期 25, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201705920
关键词
bioorthogonal chemistry; cancer therapy; iron-palladium; magnetic actuation; nanowires
类别
资金
- European Research Council Starting Grant Magnetoelectric Chemonanorobotics for Chemical and Biomedical Applications (ELECTROCHEMBOTS)
- ERC [336456]
- Short-Term Scientific Mission (STSM) Grant from the COST Action [MP1407]
- Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) [NORTE-01-0145-FEDER-000012]
- European Guidelines for the Care and Use of Laboratory Animals [Directive 2010/63/UE]
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.
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