Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK.
Chem Commun (Camb). 2012 Oct 11;48(79):9843-5. doi: 10.1039/c2cc35131e. Epub 2012 Aug 30.
Temozolomide (TMZ) is the primary chemotherapeutic agent for treatment of glioblastoma multiforme (GBM) yet it has a fast rate of degradation under physiological conditions to the 'active' MTIC, which has poor penetration of the blood-brain barrier and cellular absorption. Herein we have demonstrated binding of TMZ within the cavity of nano-container cucurbit[7]uril, resulting in a decreased rate of drug degradation. Prolonging the lifetime of the TMZ under physiological conditions through encapsulation dramatically improved the drug's activity against primary GBM cell lines as more TMZ could be absorbed by the cells before degradation. This work can potentially lead to increases in the drug's propensity for crossing the blood-brain barrier and absorption into the GBM cells, thereby increasing the efficacy of this chemotherapy.
替莫唑胺(TMZ)是治疗多形性胶质母细胞瘤(GBM)的主要化疗药物,但在生理条件下,它会迅速降解为“活性”MTIC,而 MTIC 穿过血脑屏障和被细胞吸收的能力较差。本文中,我们证明了 TMZ 可结合在纳米容器葫芦脲[7]的空腔内,从而降低了药物的降解速度。通过封装延长 TMZ 在生理条件下的寿命,可显著提高 TMZ 对原发性 GBM 细胞系的活性,因为在药物降解之前,更多的 TMZ 可以被细胞吸收。这项工作可能会增加药物穿过血脑屏障和进入 GBM 细胞的能力,从而提高这种化疗药物的疗效。