Polyphosphoester-Based Nanoparticles with Viscous Flow Core Enhanced Therapeutic Efficacy by Improved Intracellular Drug Release

The intracellular drug release rate from the hydrophobic core of self-assembled nanoparticles can significantly affect the therapeutic efficacy. Currently, the hydrophobic core of many polymeric nanoparticles which are usually composed of poly(ε-caprolactone) (PCL), polylactide (PLA), or poly(D, L-lactide-co-glycolide) (PLGA) may hinder the diffusion of drug from the core because of their glassy state at room temperature. To investigate the effect of the hydrophobic core state on therapeutic efficacy, we synthesized an amphiphilic diblock copolymers of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic polyphosphoester, which were in a viscous flow state at room temperature. The obtained copolymers self-assembled into core-shell nanoparticles, which efficiently encapsulate doxorubicin (DOX) in the hydrophobic polyphosphoester core (NP(PPE)/DOX). As speculated, compared with the nanoparticles bearing glassy core (hydrophobic PLA core, NP(PLA)/DOX), the encapsulated DOX was more rapidly released from NP(PPE)/DOX with viscous flow core, resulting in significantly increased cytotoxicity. Accordingly, the improved intracellular drug release from viscous flow core enhances the inhibition of tumor growth, suggesting the nanoparticles bearing viscous flow core show great potential in cancer therapy.