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.
