Background: Improving targeted therapy, and reducing adverse side effects of antitumor drugs toward normal cells with simultaneous bioimaging properties are being developed in pharmaceutical industries. In this study, N doped-carbon quantum dot (CQD) with ultra-high quantum yield (QY) was synthesized and its surface was modified with folic acid as the targeted anticancer agent. Methods: CQD was synthesized by one-step hydrothermal method. The impact of operating parameters such as pyrolysis temperature, time, and pH on the QY and surface charge was investigated. Then, the CQD surface was modified with folic acid as the targeted anticancer agent followed by doxorubicin (DOX) conjugation on the surface. Cytotoxicity of CQD-FA and CQD-FA-DOX upon 4T1, MCF7 and PC12 cell lines were examined. Furthermore, fluorescent microscopy imaging and flow cytometry analysis for various cell lines were applied to evaluate CQD-FA bioimaging property. In addition, the efficacy of the formulation on the BALB/c mice bearing breast cancer tumors was investigated. Results: In CQD preparation, average particle size of 7 nm was confirmed by the characterization results. With optimum synthesis conditions of pH = 11, time = 8 h and temperature = 160 ◦C, QY was about 90%. XPS analysis confirmed formation of N doped CQD. DOX loading efficiency was 88.6% and about 86% of the loaded DOX was released from CQD-FA-DOX after 72 h at pH = 5.5. Cytotoxicity analysis confirmed a higher toxicity effect of CQD-FA-DOX toward cancerous cell lines (4T1, MCF7) in comparison to free DOX. This nanocarrier could act smartly in identifying folate receptor positive cancerous cells and enter mainly by the receptor-mediated route. In vivo results showed that cellular internalization of CQD-FA-DOX was greater than free DOX, in which the tumor growth in mice treated with CQD-FA-DOX was lower than free DOX. In addition, ex vivo analysis confirmed lower side effects of CQD-FA-DOX on the main organs of mice in comparison to the free drug group. Conclusion: This new synthesized carrier can be a suitable platform for drug delivery applications with lower side effects, targeted cellular uptake and bioimaging properties.

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