Near-Infrared/pH Dual-Sensitive Nanocarriers for Enhanced Intracellular Delivery of Doxorubicin

Herein, we designed near-infrared (NIR)/pH dual-sensitive nanocarriers and evaluated its application to intracellular drug delivery. The nanocarriers were prepared based on amphiphilic poly(β-amino ester) (PBAE) containing o-nitrobenzyl moieties in the backbones and upconversion nanoparticles (UCNPs). UCNPs can convert NIR to UV that subsequently removes PEG segments from PBAE copolymers, which could enhance the protonation of PBAE in endo/lysosomes and facilitate the escape of the nanoparticles from lysosomes. In addition, we found the colocalization of the nanoparticles with mitochondria inside the cells, presumably resulting from high hydrophobicity and positive charges of the nanoparticles. The results showed that the nanocarriers with the aid of NIR could enhance the intracellular delivery of DOX, as compared with free DOX and NIR-free control. Furthermore, PBAE@UCNPs-DOX with NIR potently inhibited tumor growth in mice. Therefore, the intelligent micellar nanoparticles might provide a simple yet effective nanoplatform to achieve mitochondrion-targeting drug delivery.