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Mobile Magnetic Nanocatalysts for Bioorthogonal Targeted Cancer Therapy
Author(s) -
Hoop Marcus,
Ribeiro Ana Sofia,
Rösch Daniel,
Weinand Philipp,
Mendes Nuno,
Mushtaq Fajer,
Chen XiangZhong,
Shen Yang,
Pujante Carlos Franco,
PuigmartíLuis Josep,
Paredes Joana,
Nelson Bradley J.,
Pêgo Ana Paula,
Pané Salvador
Publication year - 2018
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201705920
Subject(s) - prodrug , immunogenic cell death , cancer research , materials science , cancer cell , viability assay , in vivo , cancer , bioorthogonal chemistry , pharmacology , nanotechnology , cell , chemistry , medicine , biology , biochemistry , click chemistry , microbiology and biotechnology , polymer chemistry
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.