NIR-triggered ligand-presenting nanocarriers for enhancing synergistic photothermal-chemotherapy

Surface PEGylation of nanomedicine is effective for prolonging blood circulation time and facilitating the EPR effect, whereas the hydrophilic stealth surface inhibits effective cellular uptake and hinders active targeting. To address the dilemma, herein, a NIR light-triggered dePEGylation/ligand-presenting strategy based on thermal decomposition of azo bonds is developed, whereby Dox/Pz-IR nanoparticle is self-assembled from thermo-labile azo molecule-linked long PEG chain polymer (Pz-IR), cRGD-conjugated IR783 with short PEG chains (rP-IR) and doxorubicin. The long PEG chains could mask cRGD peptides in the blood circulation, preventing serum degradation and nonspecific interaction with normal cells. Once exposed to NIR laser, the PEG corona is stripped off owing to the rupture of azo bonds through the photothermal effect of IR783, and the masked cRGD peptides are exposed, which remarkably enhances cellular uptake by tumor cells and improves tumor accumulation. Dox/Pz-IR achieves the optimal synergy of photothermal-chemotherapy at mild temperature through progressive tumor accumulation, precisely regulated photothermal effect and NIR-PTT induced pulsated drug release. The strategy of NIR photo-driven dePEGylation/targeting offers a new approach to overcoming the “PEG dilemma”, and provides a noval avenue for programmed tumor-targeted drug delivery.