br Herein we developed a nanoplatform

Herein, we developed a nanoplatform for simultaneous multimodal imaging and combined PDT and PTT by integrating CuS nanoparticles (PTT agents) and g-C3N4 QDs (PDT agents) on mesoporous silica-coated UCNPs, followed by modification with PEG and folic acid (FA). The design strategy of the system is to sufficiently utilize energy by choosing photothermal agent and photosensitizer with different gamma-Glu-Cys wa-velengths, which may open a new direction for the construction of functional composites. In this structure, CuS can absorb light of this wavelength and convert it to heat upon 808 nm NIR irradiation. Tm3+ ion-doped UCNPs can emit blue-violet light under the excitation of NIR light, and the blue-violet light can be absorbed by g-C3N4 QDs to pro-duce ROS [45–47]. Since the wavelengths of light absorbed by the photothermal agent CuS and the photosensitizer g-C3N4 QDs are dif-ferent, the light emitted by UCNPs can be sufficiently utilized. In ad-dition, with the help of the targeting effect of FA, the prepared nano-composite can reach the designated lesions and thus reduce harm to healthy cells in the vicinity of cancer cells.
2. Experimental section
2.1.1. Synthesis of NaGdF4:Yb,Tm nanoparticles
One mmol of RE(oleate)3 (Gd/Yb/Tm = 78:20:2), and 12 mmol of NaF were placed into a round-bottomed, three-necked flask with 15 mL OA and 15 mL ODE mixed solvent. The solution was stirred under va-cuum, warmed to 110 °C in a gradient fashion, and then maintained in this state for 30 min. Afterwards, the temperature of the mixed solvent continued to rise. After the temperature was increased to 300 °C and maintained at that level for 90 min under nitrogen, the temperature was decreased to approximately 20 °C. Finally, NaGdF4:Yb,Tm nanoparticles were obtained via centrifugation.
2.1.2. Synthesis of NaGdF4:Yb,Tm@NaGdF4:Nd,Yb nanoparticles Typically, the above nanoparticles were placed in a reaction vessel,
followed by 15 mL OA and 15 mL ODE. Thereafter, 0.5 mmol of RE (CF3COO)3 (Gd/Yb/Nd = 6:3:1) and 1 mmol of CF3COONa were placed into the container. The solution was stirred under vacuum, warmed to 120 °C in a gradient fashion, and then kept in this state for 40 min. Afterwards, the mixture was heated to 310 °C and maintained for 60 min in N2. When the temperature decreased to approximately 20 °C, the core-shell nanoparticles were obtained via centrifugation and wa-shed several times for further use. The prepared NaGdF4:Yb,Tm@ NaGdF4:Yb,Nd UCNPs were named as UCNPs.
2.1.3. Synthesis of UCNPs@mSiO2 nanocomposite UCNPs@mSiO2 nanocomposite was acquired by the modified
procedure which we previously reported [48]. Briefly, 2 mL solution with a certain concentration of UCNPs (approximately 5–10 mg mL−1) and 0.1 g cetyltriethylammnonium bromide (CTAB) were added into 20 mL of deionized water. The mixture solution was then vigorously stirred at room temperature overnight to remove the cyclohexane. Thereafter, 10 mL of UCNPs aqueous solution modified with CTAB was added to NaOH solution (150 μL, 2 mol L–1), deionized water (20 mL) and ethanol (3 mL), respectively. The mixture was warmed to 70 °C under magnetic stirring. Next, 100 μL of tetraethylorthosilicate (TEOS) was added dropwise into the mixture and vigorously stirred for ap-proximately 10 min. The prepared sample was acquired by centrifuga-tion and washed three times. The template CTAB was then removed by the following method. 20 mg of the prepared UCNPs@mSiO2 was placed in a reaction vessel containing 0.3 g NH4NO3 with 60 mL ethanol and refluxed at 60 °C for 2 h. Finally, the synthesized UCNPs@mSiO2 nanocomposite spheres were attained for further use.
2.1.4. Synthesis of UCNPs@mSiO2-CuS (USCs) nanocomposite
First, 100 mg of UCNPs@mSiO2 nanoparticles was placed in a so-lution containing 60 mL ethanol, and then 500 μL APTES was added into the solution. The solution was gently heated to 40 °C and stirred for 10 h. Then, the UCNPs@mSiO2–NH2 were recovered by centrifugation and washed three times. After that, 10 mg UCNPs@mSiO2–NH2 was put into 30 mL of the previously prepared CuS solution (see supporting information for the detailed synthesis of CuS nanoparticles). Positively charged UCNPs@mSiO2–NH2 and negatively charged CuS nano-particles are chromosome theory of inheritance connected by an electrostatic adsorption interaction. After vigorously stirring for 2 h, the sample was prepared via centrifugation.
First, the g-C3N4 QDs prepared above (see supporting information for details) were added into 10 mg USCs, stirred for 1 h and then cen-trifuged to obtain g-C3N4-UCNPs@mSiO2-CuS (CUSCs) nanocomposite material. Then, 50 mg NH2-mPEG-COOH was placed into the above solution and stirred for 24 h. Next, 5 mg FA, 10 mg EDC and 8 mg NHS were mixed into 15 mL water and reacted in darkness for 4 h at room temperature. Subsequently, the prepared CUSCs-PEG nanocomposite was put into the above solution and stirred one entire night in darkness. Eventually, the sample was collected by centrifugation and washed with deionized water several times.