Morphology Control of Phosphorescent CDs@SiO 2 in Aqueous Solution and Application in Liver Cancer Theranostic Drug Delivery

Early diagnosis and precise treatment of liver cancer represent critical directions in medical research. Theranostic strategies integrating bioimaging and drug delivery have demonstrated significant potential, offering advantages such as high precision, enhanced imaging clarity, and improved therapeutic efficacy. Room temperature phosphorescence carbon dots@silica composites (RTP CDs@SiO2) stand out in bioimaging for their excellent properties such as long phosphorescence lifetime and low toxicity. However, their irregular morphology and large particle size restrict applications in drug delivery. In this study, RTP CDs@SiO2 composites were synthesized in an an aqueous solution via three approaches with different alkaline additives: no alkaline additive, ammonia solution, and arginine. Through the synergistic effect of the guanidine group, amino group, and carboxyl group in arginine molecules, nanoparticles with an average particle size of 14.2 nm, a phosphorescence lifetime of 1398.91 ms, and a visible afterglow duration of 12 s were prepared. The resultant composites possessed favorable biocompatibility with low toxicity, as well as outstanding phosphorescence imaging performance both in vitro and in vivo. The RTP CDs drug delivery system (CDs@SiO2-HA-DOX) was further constructed by loading the targeting molecule hyaluronic acid (HA) and the chemotherapy drug doxorubicin (DOX) via electrostatic adsorption and covalent coupling using CDs@SiO2 as a carrier. Results demonstrated that this system achieved a maximum drug loading capacity of 49.39% and exhibited pH-dependent DOX release under weakly acidic conditions. In vitro antitumor experiments revealed that CDs@SiO2-HA-DOX reduced the viability of HepG2 cells to 22.95%. In vivo studies using tumor-bearing mouse models confirmed a tumor inhibition rate of 75.48%, demonstrating significant antitumor efficacy. This work represents the first successful application of RTP CD composites in drug delivery. The developed system shows great promise as a theranostic candidate for liver cancer by integrating drug delivery and RTP imaging, highlighting its significant potential for cancer therapy applications.