Dual Drug Backboned Shattering Polymeric Theranostic Nanomedicine for Synergistic Eradication of Patient‐Derived Lung Cancer

Abstract 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.