Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet-Hydrogel Frameworks
Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet-Hydrogel Frameworks
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DOI：
10.1021/acs.jmedchem.0c00781
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发表时间：
2020-09-10
影响因子：
7.3
通讯作者：
Unciti-Broceta, Asier
中科院分区：
文献类型：
--
作者：
Perez-Lopez, Ana M.;Rubio-Ruiz, Belen;Unciti-Broceta, Asier
生物正交催化在生物医学领域的巨大潜力激发了人们在生物系统中设计药物活性调控策略的努力。为了实现这一目标，不仅需要开发定制的非活性前药和生物相容性金属催化剂，还需要为它们相互作用创造合适的物理环境，并使药物生产在空间和/或时间控制下进行。为了实现这一目标，在这里，我们报道了强效广谱抗癌药物紫杉醇（又名紫杉醇）的第一个无活性前体，它在细胞培养中稳定，对Pd催化剂不稳定。这种新的前药通过琼脂糖和海藻酸盐水凝胶捕获的Pd纳米片有效地在癌细胞培养中释放，为实现医学实践中最重要的化疗药物之一的控制释放提供了可生物降解的催化框架。生物正交催化和物理水凝胶的相容性为在生活环境中管理和调节过渡金属催化剂的迁移性开辟了新的机会。
The promising potential of bioorthogonal catalysis in biomedicine is inspiring incremental efforts to design strategies that regulate drug activity in living systems. To achieve this, it is not only essential to develop customized inactive prodrugs and biocompatible metal catalysts but also the right physical environment for them to interact and enable drug production under spatial and/or temporal control. Toward this goal, here, we report the first inactive precursor of the potent broad-spectrum anticancer drug paclitaxel (a.k.a. Taxol) that is stable in cell culture and labile to Pd catalysts. This new prodrug is effectively uncaged in cancer cell culture by Pd nanosheets captured within agarose and alginate hydrogels, providing a biodegradable catalytic framework to achieve controlled release of one of the most important chemotherapy drugs in medical practice. The compatibility of bioorthogonal catalysis and physical hydrogels opens up new opportunities to administer and modulate the mobility of transition metal catalysts in living environs.