Doxorubicin is an effective and widely used cancer chemotherapeutic agent, but its application is greatly compromised by its cumulative dose-dependent side effect of cardiotoxicity. A gold nanoparticle-based drug delivery system has been designed to overcome this limitation. Five novel thiolated doxorubicin analogs were synthesized and their biological activities evaluated. Two of these analogs and PEG stabilizing ligands were then conjugated to gold nanoparticles, and the resulting Au-Dox constructs were evaluated. The results show that release of native drug can be achieved by the action of reducing agents such as glutathione or under acidic conditions, but reductive drug release gave the cleanest drug release. Gold nanoparticles (Au-Dox) were prepared with different loadings of PEG and doxorubicin, and one formulation was evaluated for mammalian stability and toxicity. Plasma levels of doxorubicin in mice treated with Au-Dox were significantly lower than in mice treated with the same amount of doxorubicin, indicating that the construct is stable under physiological conditions. Treatment of mice with Au-Dox gave no histopathologically observable differences from mice treated with saline, while mice treated with an equivalent dose of doxorubicin showed significant histopathologically observable lesions.

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载有阿霉素的金纳米颗粒的合成及评价

阿霉素是一种有效且广泛使用的癌症化学治疗剂，但是其应用受到心脏毒性累积剂量依赖性副作用的影响。已经设计了基于金纳米颗粒的药物递送系统来克服该限制。合成了五个新颖的硫醇化阿霉素类似物，并对其生物学活性进行了评估。然后将其中两个类似物和PEG稳定配体与金纳米颗粒偶联，并评估所得的Au-Dox构建体。结果表明，通过还原剂（如谷胱甘肽）或在酸性条件下可以实现天然药物的释放，但是还原性药物的释放提供了最干净的药物释放。制备了金纳米颗粒（Au-Dox），其中包含不同含量的PEG和阿霉素，评估了一种配方的哺乳动物稳定性和毒性。用Au-Dox处理的小鼠中的阿霉素血浆水平显着低于用相同量的阿霉素处理的小鼠中的阿霉素，表明该构建体在生理条件下是稳定的。用Au-Dox处理小鼠与用盐水处理的小鼠没有在组织病理学上可观察到的差异，而用等剂量的阿霉素处理的小鼠则显示出明显的在组织学上可观察到的损伤。