br g and the mice were naturally divided
(20–25 g) and the mice were naturally divided into 5 groups, including normal saline, NIR irradiation, CUSs nanocomposite + 808 nm NIR, USCs nanocomposite + 808 nm NIR and CUSCs-PEG-FA nanocompo-site + 808 nm NIR. Notably, mice treated with normal saline were used as controls. In addition, the remaining groups were stimulated with 808 nm NIR light for 10 min after injection of diﬀerent materials for 4 h, respectively. Tumor size was measured with a caliper every 2 days after therapy.
2.11. Histology examination
The histological analysis was performed after 14 days of treatment. The typical organs (heart, liver, spleen, lung and kidney) and tumor tissue of each group of mice were dissected. The anatomical tissues were then continuously dehydrated by various concentrations of ethanol and buﬀered formalin. The dehydrated tissues were embedded in liquid paraﬃn and sectioned for hematoxylin and eosin (H&E) staining. The ultimate stained sectioned were observed by an optical microscope.
3. Results and discussion
3.1. Synthesis and characterization of samples
The synthesis of CUSCs-PEG-FA nanocomposite and application for multimodal image-guided PTT/PDT in vitro and in vivo are schemati-cally illustrated in Scheme 1a-b. As presented in the TEM image (Fig. 1a), NaGdF4:Yb,Tm nanoparticles are uniformly dispersed and have a diameter of approximately 23 nm. The external shell layer of NaGaF4:Yb,Nd was then sequentially coated onto the NaGdF4:Yb,Tm
Scheme 1. (a) Schematic illustration of the synthesis of CUSCs-PEG-FA nanocomposite. (b) Application for multimodal imaging-guided PTT/PDT of CUSCs-PEG-FA in vitro and in vivo.
core by a continuous growth process, and core–shell structured UCNPs with mean diameter of 27 nm were obtained (Fig. 1b). Afterwards, the hydrophobic UCNPs were converted into LY 379268 analogues by capping molecules (CTAB), which were used as a surfactant to further form a mesoporous silica shell. In Fig. 1d, [email protected] nanoparticles
are also well dispersed with an average diameter of 83 nm. Ad-ditionally, it is clear that the CuS nanoparticles (Figure S1a) uniformly disperse with a diameter approximately 6–10 nm. After CuS nano-particles were prepared, two steps were adopted to combine CuS par-ticles on the [email protected] nanocomposite by the opposite charges on
CUSCs-PEG-FA. (b) XPS survey spectrum of CUSCs.
both surfaces. First, the positively charged amino groups (–NH2) of APTES were connected to the surface of [email protected] to produce a positive charge of 26.18 mV. Second, CuS nanoparticles with a negative charge of –23.49 mV were conjugated onto the surface of UCNPs@ mSiO2-NH2 by an electrostatic adsorption technique (Fig. 1e and Figure S1b). The prepared g-C3N4 QDs are composed of ultrasmall nano-particles, and the mean diameter is approximately 2 nm (Fig. 1c and Figure S1c-d). Since the average diameters of g-C3N4 QDs are too small, it is diﬃcult to detect them clearly in the TEM image of CUSCs (Fig. 1f). In particular, USCs with a positive charge of 5.94 mV can also adhere to g-C3N4 QDs with a negative charge of −28.67 mV by electrostatic in-teraction (Figure S1b). Meanwhile, in Figure S1b, both photosensitive materials of CuS nanoparticles and g-C3N4 QDs were negatively charged. Based on the high negative charge, the solutions of CuS na-noparticles and g-C3N4 QDs are very stable and do not aggregate even after several months of standing. Furthermore, energy dispersive spectrometry (EDS) can clearly indicate the occurrence of the C, N, O, Cu, Si, S and other elements among the nanoparticles (Fig. 1g), proving that CuS and g-C3N4 QDs are successfully connected. Furthermore, the surface properties of the prepared samples were further analyzed by Fourier transform infrared (FT-IR) spectroscopy (Fig. 1h). In the FT-IR spectrum of UCNPs (Fig. 1h(1)), the broad peak at 3436 cm−1 is at-tributed to the O–H stretching vibration. Peaks at 2934 cm−1 and