Abstract:
Although Warburg discovered pH discrepancies between tumor and normal tissues nearly 100 years ago, developing therapies to take advantage of this concept was relatively slow for the first 70 years. During the last 30 years, there has been an exponential increase in the use of pH-dependent strategies for both low molecular weight drugs and nanoparticles. Two frequently discussed approaches are the chemotherapy\'s release from pH-sensitive covalent linkages of macromolecules or from pH-dependent disruption of charged polymeric nanoparticles. In contrast, pH-dependent non-covalent bonds between the chemotherapy agent and macromolecules have rarely been discussed, yet this underappreciated strategy has great potential. These non-covalent interactions are primarily ionic or hydrogen bonds with supporting roles from hydrophobic bonds. In addition to the facile coupling of the drug with the carrier, these non-covalent interactions may show marked pH dependence. Consistent with pH dependence, many of these drug-loaded carriers showed significant in vitro and, in some cases, striking in vivo activity. In this review, we will focus on pH-sensitive non-covalent bonds, highlighting the release of drugs from diverse carriers such as tetrahedron DNA structures, cyclodextrin, polymeric carriers, and carbon-based quantum particles.
摘要:
尽管Warburg在近100年前发现了肿瘤和正常组织之间的pH差异,在最初的70年中,开发利用这一概念的疗法相对较慢。在过去的30年里,低分子量药物和纳米颗粒对pH依赖性策略的使用呈指数增长.两种经常讨论的方法是化学疗法从大分子的pH敏感共价连接或从带电聚合物纳米颗粒的pH依赖性破坏释放。相比之下,很少讨论化疗药物和大分子之间的pH依赖性非共价键,然而,这种被低估的战略有很大的潜力。这些非共价相互作用主要是离子键或氢键,具有来自疏水键的支持作用。除了药物与载体的容易偶联外,这些非共价相互作用可能显示出显著的pH依赖性。与pH依赖性一致,这些载药载体中的许多在体外表现出显著的作用,在某些情况下,惊人的体内活动。在这次审查中,我们将专注于pH敏感的非共价键,突出药物从不同的载体如四面体DNA结构的释放,环糊精,聚合物载体,和碳基量子粒子.