Polyethyleneimine/gold nanorods conjugated with carbon quantum dots and hyaluronic acid for chemo-photothermal therapy of breast cancer

The aim of this study was to develop a stable polyethyleneimine/gold nanorod composite conjugated with a carbon quantum dot (CQD) and hyaluronic acid (HA) complex (CQD-HA-PEI@GNRs) for applications in chemotherapy and photothermal therapy. GNRs were synthesized using a seed-mediated growth method, and the amount of seed solution was optimized to obtain GNRs with an optimal aspect ratio and a strong peak in the near-infrared (NIR) region. The surface of the GNRs was then modified with polyethylene imine (PEI). In parallel, CQDs were synthesized through a hydrothermal method and subsequently conjugated with HA to act as an active targeting ligand. The resulting CQD-HA complex was loaded onto the surface of the PEI@GNR composite. Finally, the anticancer drug doxorubicin (DOX) was effectively loaded onto this innovative complex. The cytotoxicity of the final complex was evaluated on different cell lines in the presence and absence of laser irradiation. Furthermore, the efficacy of the formulation was investigated in BALB/c mice bearing breast cancer tumors. Characterization results confirmed the successful formation of GNRs with a length of 40 nm, exhibiting a strong peak at 813 nm in the NIR region. The zeta potential value of the GNRs was -25.62 mV, which increased to +40.59 mV after the surface modification with PEI. CQDs were synthesized and successfully conjugated with HA. DOX encapsulation efficiency was 92.8%, with appropriate drug release profiles in the presence of laser irradiation. The final complex showed appropriate cytotoxicity toward 4T1 and MCF7 breast cancer cell lines. <i>In vivo</i> analysis of the CQD-HA-PEI@GNR-DOX complex combined with laser treatment demonstrated significant tumor growth inhibition in comparison to the control group. Finally, this novel complex was proposed as an alternative for breast cancer treatment.