A mixed drug self-delivery system (DSDS) with high drug content (>50%) was developed to regulate pH-triggered drug release, based on two doxorubicin (DOX)-DOX dimmers: D-DOX_ADH and D-DOX_car conjugated with acid-labile dynamic covalent bonds (hydrazone and carbamate, respectively) and stabilized with PEGylated D-DOX_ADH (D-DOX_ADH-PEG). Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them, pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS. Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios. The mixed DSDS nanoparticles had a similar DOX content and diameter but different drug releasing rates. The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slow-release mixed DSDS nanoparticles.

_{基于两种阿霉素 (DOX)-DOX 二聚体：D-DOX ADH}和 D-DOX_汽车偶联物，开发了一种高药物含量 (>50%) 的混合药物自递送系统 (DSDS)，用于调节 pH 触发的药物释放具有酸不稳定的动态共价键（分别为腙和氨基甲酸酯），并用聚乙二醇化 D-DOX _ADH (D-DOX _ADH -PEG) 稳定。由于两个二聚体中动态共价键的稳定性不同以及它们之间的非共价相互作用，通过调整混合DSDS中两个DOX-DOX二聚体的投料比可以轻松调节pH触发的药物释放。用不同的投料比制备的混合 DSDS 纳米粒子也实现了类似的体外细胞毒性。混合的 DSDS 纳米颗粒具有相似的 DOX 含量和直径，但药物释放速率不同。MTT 分析表明，缓释混合 DSDS 纳米颗粒具有较高的抗肿瘤功效。