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Dual Drug Backboned Shattering Polymeric Theranostic Nanomedicine for Synergistic Eradication of Patient-Derived Lung Cancer
writer:Y. Cong, H. Xiao#, H. Xiong, Z. Wang, J. Ding, C. Li, X. Chen*, X. Liang*, D. Zhou*, Y. Huang
keywords:Dual sensitivity, shattering polymer, precise nanomedicine, patient-derived tumor, computer tomography
specific source:Advanced Materials
Issue time:2018年

Most of current nanoparticle-based therapeutics worldwide failing in clinical trials can be mostly attributed to three major challenges: i) lack of optimum drug delivery platform with precise composition, ii) lack of way of directly monitoring the fate of a specific drug rather than using any other labelling molecules for 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, we show the design of a dual sensitive dual drug backboned shattering polymer (DDBSP) with exact composition at a fixed DMC/Pt ratio for precise nanomedicine. DDBSP self-assembled NPs (DD-NP) could be triggered intracellularly to breakdown in a chain-shattering manner to release the dual drugs payload. Moreover, DD-NP with extremely high contents of Pt heavy metals 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, we use DD-NP to eradicate the tumor burden on a high fidelity patient-derived lung cancer model for the first time.