PH- and Enzyme-Sensitive IR820-Paclitaxel Conjugate Self-Assembled Nanovehicles for Near-Infrared Fluorescence Imaging-Guided Chemo-Photothermal Therapy.

Abstract

The short lifetime and easy quick elimination of the near-infrared (NIR) dye new indocyanine green (IR820) in the body restrict its practical application as a photothermal agent in cancer therapy. Meanwhile, the drawback of poor water solubility of the chemotherapeutic drug paclitaxel (PTX) largely restricts its clinical applications. Herein, we, for the first time, combined IR820 and PTX in an "all-in-one" fluorescence imaging-guided chemo-photothermal therapy (PTT) platform by a rational design of a novel pH- and enzyme-sensitive IR820-PTX conjugate assembly. Specifically, the IR820-PTX conjugate nanoparticles exhibit an extremely high therapeutic agent content (IR820 and PTX, 95.7%). Besides the good stability in bloodstream, the IR820-PTX nanoparticles can target tumors for high accumulation via the enhanced permeation and retention effect. Particularly, our IR820-PTX nanoparticles simultaneously solve the obstacles of PTX poor solubility and the short lifetime of IR820 for cancer therapy. The simultaneous release of the free drug and dye can efficiently kill tumor cells by the combination of PTT and chemotherapy via NIR irradiation. Furthermore, the combined therapy can be imaging-guided by measuring the NIR fluorescence imaging resulting from the IR820 component. Therefore, our rationally designed pH- and enzyme-sensitive IR820-PTX conjugate nanoparticles provide an alternative "all-in-one" option for an efficient combinational dual-therapy and imaging.