Synergistic chemotherapy and phototherapy co-delivery nanoparticle preparation and anti-triple negative breast cancer study

Abstract

In this study, the amphiphilic polymer HA–ANI, formed by grafting hyaluronic acid (HA) and 6-(2-nitroimidazolyl)hexylamine (ANI), was self-assembled in water to form nanoparticles (NPs), which were modified to obtain dual drug-loaded nanoparticles (P/I NPs) by dialysis loading of paclitaxel (PTX) and IR780. Electron microscopy and dynamic light scattering (DLS) results showed that the P/I NPs presented a near-spherical shape with a size of 221.10 ± 2.31 nm. The drug loading and encapsulation rates of PTX in P/I NPs were 22.73% and 89.23%, respectively, and those of IR780 were 1.11% and 42.44%, respectively. In vitro release experiments demonstrated that NADPH could accelerate the drug release from the NPs. Under the irradiation of an NIR laser, the temperature of the P/I NPs increased significantly. In an in vitro cellular assay treating 4T1 cells for 24 h, the cellular uptake rate of NPs could reach 91.50 ± 3.51%, the 4T1 cell migration rate was 2.68 ± 0.34%, the cell viability was 39.96 ± 0.55%, and the apoptotic cell death rate was 13.93 ± 0.42%. In an in vivo anti-tumor experiment, the inhibition rate of the P/I NPs towards tumors was up to 35.44%; the fluorescence intensity at the tumor site gradually increased with time, and the maximum value appeared within 24 h, indicating that the P/I NPs had a targeting function. The results of H&E staining showed that there was no obvious pathological damage to the main organs of the mice in each group, that means there were no obvious side effects.