The aim of this study was to develop a stable polyethyleneimine/gold nanorod conjugated with carbon quantum dot (CQD) and hyaluronic acid (HA) complex (CQD-HA-PEI@GNR) for application 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 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 was loaded onto the surface of the PEI@GNR. Finally, doxorubicin (DOX) anticancer drug 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 successful formation of GNRs with 40 nm in length, exhibiting a strong peak at 813 nm in the NIR region. The zeta potential value for 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. Doxorubicin encapsulation efficiency was 92.8%, with appropriate drug release curve at the presence of laser irradiation. The final complex showed appropriate cytotoxicity toward 4T1 and MCF7 breast cancer cell lines. In vivo 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.

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