Supramolecular nanoparticles self-assembled from reduction-responsive cabazitaxel prodrugs for effective cancer therapy

Using hydrophobic cabazitaxel as a target anticancer drug, we show that the conjugation of oligo(ethylene glycol)-oligolactide (OEG-OLA) via a self-immolative linkage induces the self-assembly of the resulting prodrug into injectable nanoparticles. The nanoparticles release chemically unmodified cabazitaxel after endocytosis in cancer cells. With the optimal conjugate, the nanotherapy not only potently induces tumor regression but also has a higher safety margin in animals than the free drug administered in its clinical formulation. Our studies highlight the design rationale that attaching a short amphiphilic oligomer to a toxic drug can convert it to a self-deliverable and safe nanotherapy.

Automated summary

The study demonstrates that conjugating hydrophobic drugs with oligo(ethylene glycol)-oligolactide leads to the formation of injectable nanoparticles, which release chemically unmodified drugs inside cancer cells, effectively inducing tumor regression with a higher safety margin in animals. This highlights the potential of using short amphiphilic oligomers to convert toxic drugs into self-deliverable and safe nanotherapies.