Most of the current nanoparticle‐based therapeutics worldwide failing in clinical trials face three major challenges: (i) lack of an optimum drug delivery platform with precise composition, (ii) lack of a method of directly monitoring the fate of a specific drug rather than using any other labelling molecules as a compromise, and (iii) lack of reliable cancer models with high fidelity for drug screen and evaluation. Here, starting from a PP2A inhibitor demethylcantharidin (DMC) and cisplatin, the design of a dual sensitive dual drug backboned shattering polymer (DDBSP) with exact composition at a fixed DMC/Pt ratio for precise nanomedicine is shown. DDBSP self‐assembled nanoparticle (DD‐NP) can be triggered intracellularly to break down in a chain‐shattering manner to release the dual drugs payload. Moreover, DD‐NP with extremely high Pt heavy metal content in the polymer chain can directly track the drug itself via Pt‐based drug‐mediated computer tomography and ICP‐MS both in vitro and in vivo. Finally, DD‐NP is used to eradicate the tumor burden on a high‐fidelity patient‐derived lung cancer model for the first time.

中文翻译：

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双重药物粉碎的聚合物治疗性纳米药物可协同根除患者来源的肺癌。

目前，全球大多数在临床试验中失败的基于纳米颗粒的疗法都面临着三个主要挑战：（i）缺乏具有精确组成的最佳药物递送平台，（ii）缺乏直接监测特定药物命运的方法，而不是直接监测特定药物命运的方法使用任何其他标记分子作为折衷方案，以及（iii）缺乏可靠且高保真度的癌症模型用于药物筛选和评估。在这里，从PP2A抑制剂脱甲基邻苯二酚（DMC）和顺铂开始，显示了双敏感双药主链粉碎聚合物（DDBSP）的设计，该化合物具有精确的组成，且DMC / Pt比例固定，可用于精确的纳米药物。DDBSP自组装纳米颗粒（DD-NP）可以在细胞内触发，以链断裂的方式分解，释放出双重药物有效载荷。而且，高分子链中Pt重金属含量极高的DD‐NP可以在体外和体内通过基于Pt的药物介导的计算机断层扫描和ICP‐MS直接跟踪药物本身。最后，DD-NP首次用于根除高保真患者来源的肺癌模型上的肿瘤负担。