Detalhes bibliográficos
| Autor(a) principal: |
Hoop, M |
| Data de Publicação: |
2018 |
| Outros Autores: |
Ribeiro, AS,
Rösch, D,
Weinand, P,
Mendes, N,
Mushtaq, F,
Chen, X,
Shen, Y,
Pujante, C,
Puigmartí-Luis, J,
Paredes, J,
Nelson, B,
Pêgo, AP,
Pané, S |
| Tipo de documento: |
Artigo
|
| Idioma: |
eng |
| Título da fonte: |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: |
https://hdl.handle.net/10216/121100
|
Resumo: |
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. |