Joint Strategy of PEG-PEI/CDs-E64d Nanoagents for Effective Low-Temperature Photothermal Therapy

Near infrared (NIR)-triggered photothermal therapy (PTT) usually requires hyperthermia for effective tumor therapy, leading to side effects such as overheating damage. It is critical and challenging for the successful clinical application of PTT through achieving effective tumor therapy under mild temperature. Herein, a joint strategy of autophagy inhibition and lysosomal escape based on PEG-PEI/CDs-E64d nanoagents was designed using PEG as a carrier to combine PEI with “proton sponge” effect and autophagy inhibitor of E64d, which improved the sensitivity of tumor cells to treatment and the utilization of photothermal agent (carbon quantum dots, CDs), and were characterized in detail by transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), Zeta, Western blot, etc. The excellent photothermal effect, autophagy inhibition and lysosomal escape ability were proved in vitro experiments, and the results of in vivo experiment showed the effective and safe low-temperature PTT effect was achieved with tumor inhibition rate of 84.3% for 9 days of treatment at 42 °C. In general, the joint strategy we proposed provides a useful exploration for the clinical application of PTT. Graphical Abstract