pH-responsive hyaluronic acid nanoparticles codelivering DOX and ICG for effectively chemo-photothermal combination therapy

Insufficient cumulative release of chemotherapeutics at the tumor site and poor efficacy of monotherapy are the main reasons for the unsatisfactory effect of cancer therapy at present. Here, a pH-responsive nanoparticle (DAH@ICG NP) based on hyaluronic acid (HA) was designed which was loaded with the photosensitizer indocyanine green (ICG) and chemotherapeutic doxorubicin (DOX) for chemo-photothermal combination therapy against cancer. Besides, the in vitro stability, acid-sensitive release behavior, photothermal efficiency, in vitro cytotoxicity, and cell selectivity index of the DAH@ICG NPs were evaluated. Accordingly, the DAH@ICG NPs had a hydrodynamic particle size of 150.3 nm. The drug loading of DOX and ICG in the DAH@ICG(5-1) NPs was 21.2% and 10.40%, respectively. What's more, compared with human umbilical vein endothelial cells (HUVECs), in vitro cytotoxicity assay against 4T1 cells showed that the nano-delivery system showed higher cell-killing performance and the cell selectivity index (selectivity index = 9.52). More importantly, the cellular uptake of the laser-irradiated group was significantly enhanced owing to the heat generated by the photosensitizer ICG, which can improve cell membrane fluidity and destroy the extracellular matrix. Taken together, DAH@ICG NPs may be promising nanoplatforms to achieve a synergistic therapeutic effect for the combination of chemotherapy and photothermal therapy (PTT).