On the one hand, the active Pt(IV) conjugated polymeric prodrug could exhibit rapid release according to the reduction environment after cellular internalization, on the other hand, cationic nanoparticles could extravasate into tumors and ultimately enter tumor cells significantly. Based on this, we have developed an integrated nanoparticles platform through self-assembly of a biodegradable poly(ethylene glycol)-block-poly(lactide) (PEG-PLA), a hydrophobic polylactide-cisplatin prodrug, and a cationic lipid by single emulsification method. Thus, this delivery system with high biocompatibility can not only stabilize by PEG protection to extend its life-time in vivo, but also improve tumor uptake by positive charge mediated extravasation. Additionally, the Pt(IV) prodrug was reduced by cellular reducing agents and liberated from the polymer to recover its activity, resulting in increased intracellular drug concentration and reversal of cisplatin resistance.

This study has recently been published in Biomaterials (10.1016/j.biomaterials.2016.04.001) titled “Overcoming tumor resistance to cisplatin by cationic lipid-assisted prodrug nanoparticles”. This work is supported by National Basic Research Program of China and National Nature Science Foundation of China.