Near-infrared and pH-responsive carbon dots/bergenin for biological imaging and chemo-photothermal synergistic tumor therapy.

Photothermo-chemotherapy has shown a synergistic anti-cancer efficiency and can enhance the therapeutic effect of simple chemotherapy. The photothermal conversion characteristics of carriers are vital in photothermal chemotherapy. In this study, we developed functional carbon dots (CDs) as a photothermal agent and carrier to load bergenin (Ber) for simultaneous biological imaging and photo-chemothermal synergistic therapy. CDs were successfully synthesized using a one-step solvothermal method with citric acid and polyethyleneimine in formamide. Surface morphology, chemical composition and structure, luminescent properties, and photothermal properties of synthesized CDs and CDs/Ber were investigated. The CDs (<10 nm) displayed a mono-dispersed state and uniform spherical morphology with a graphite-like structure. Ber was loaded onto CDs by π-π stacking and intermolecular hydrogen bonds, with a high drug loading efficiency of 95.8 %. In vitro release studies verified pH-dependent sustained drug release, with release rates of 37.84 ± 1.67 % (pH 6.5) and 29.19 ± 0.28 % (pH 7.4), which conformed to the Weibull model. The CDs/Ber had excellent photothermal performance, stability, and high conversion efficiency (54.9 %) by non-radiative transitions. The CDs acted as an ideal theranostic and photothermal agent for fluorescence imaging, photothermal imaging, ablation, and necrosis of cancer cells. CDs/Ber exhibited excellent water-solubility, biocompatibility, and passive tumor-targeting capability. Cytotoxicity experiments proved that combined therapy of CDs/Ber induced the highest cell-killing level. The biodistribution and pharmacodynamics experiments of CDs/Ber in the lung tumor model within 14 days post-exposure to one-time near-infrared radiation (NIR) irradiation indicated that CDs prolonged the residence time of Ber in tumor tissues and actualized effective synergistic photothermal chemotherapy, yielding a true "1 + 1 > 2" effect. The results of this study indicated that CDs/Ber had great potential in dual-triggered drug delivery and photothermal-chemotherapy, and acted as an excellent candidate for efficient cancer therapy.