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Mobile Magnetic Nanocatalysts for Bioorthogonal Targeted Cancer Therapy
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2018-01-15 , DOI: 10.1002/adfm.201705920
Marcus Hoop 1 , Ana Sofia Ribeiro 2, 3 , Daniel Rösch 1 , Philipp Weinand 1 , Nuno Mendes 2 , Fajer Mushtaq 1 , Xiang-Zhong Chen 1 , Yang Shen 4 , Carlos Franco Pujante 5 , Josep Puigmartí-Luis 5 , Joana Paredes 2, 3 , Bradley J. Nelson 1 , Ana Paula Pêgo 6, 7, 8 , Salvador Pané 1
Affiliation  

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.

中文翻译:

用于磁性生物靶向癌症的移动磁性纳米催化剂

使用磁性纳米机器人激活化学疗法的前药代表了当前化学疗法的有前途的替代方法。在这里,提出了一种在体外和体内癌症模型中靶向生物正交驱动潜在化学治疗前药5-氟-1-炔丙基尿嘧啶(Pro-5-FU)的杂交纳米线(NW)。NW由已知的生物正交催化剂磁性铁(Fe)和钯(Pd)组成。用癌细胞系进行的体外试验表明,NWs没有明显的细胞毒性作用。相比之下,NWs与Pro-5-FU结合会导致细胞活力的显着降低,类似于其活性化学疗法对应物5-氟尿嘧啶(5-FU)所诱导的细胞活力。细胞活力的降低归因于Pro-5-FU催化活化为5-FU。为了证明其靶向治疗能力,使用磁场将FePd NW吸引到培养的癌细胞群内的预定区域,引起局部Pro-5-FU活化,并随后在该区域造成细胞死亡。作为概念的证明,将NWs注射入癌症肿瘤异种移植物中。腹膜内注射Pro-5-FU可显着延缓肿瘤的生长,而不会引起明显的副作用。这项工作提出了一种新颖的化学治疗方法,结合了纳米药物和前药的生物正交激活,可作为常规化学疗法的有效替代方法。将NWs注射入癌症肿瘤异种移植物中。腹膜内注射Pro-5-FU可显着延缓肿瘤的生长,而不会引起明显的副作用。这项工作提出了一种新颖的化学治疗方法,结合了纳米药物和前药的生物正交激活,可作为常规化学疗法的有效替代方法。将NWs注射入癌症肿瘤异种移植物中。腹膜内注射Pro-5-FU可显着延缓肿瘤的生长,而不会引起明显的副作用。这项工作提出了一种新颖的化学疗法,结合了纳米药物和前药的生物正交激活,可以作为传统化学疗法的有效替代方法。
更新日期:2018-01-15
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