A "win-win" nanoplatform: TiO2:Yb,Ho,F for NIR light-induced synergistic therapy and imaging.

To avoid the defect of low energy transfer efficiency in core-shell UCNP-TiO2 NPs, doping rare earth into TiO2 and improving the photocatalytic activity of TiO2 itself under Vis-NIR light might be a more direct and efficient strategy for high 1O2 production. Here, we designed a TiO2:Yb,Ho,F-β-CD@DTX/HA nanoplatform using TiO2:Yb,Ho,F as the core, β-CD as the drug carrier, hyaluronic acid (HA) as the capping agent and target, and then applied it for 808 nm induced photodynamic-chemotherapy and 980 nm upconversion fluorescence/MR imaging. The results were as follows: (i) for TiO2 as a photosensitizer, after doping Yb, Ho, F into TiO2, it could directly generate reactive oxygen species under an 808 nm laser; the dopants enhanced the absorption under the UV-Vis-NIR region and increased the electron-hole pair separation. (ii) For TiO2 as the upconversion host, F and Ho also endowed TiO2:Yb,Ho,F with enhanced upconversion fluorescence under a 980 nm laser and T2-MRI contrast performance (r2 = 30.71 mM-1 s-1), respectively, thus, facilitating imaging for deep tissues. (iii) The HA shell outside of β-CD prevented the unexpected leaking of DTX, which improved the target abilities and achieved the enzyme-responsive drug release. The in vitro and in vivo studies also demonstrated the nanosystem could efficiently suppress tumor growth by combination therapy and had excellent imaging (UCL/MR) ability. Particularly, our work was the first example that utilized TiO2 simultaneously as a photosensitizer and upconversion host, which simplified the core-shell UCNP-TiO2 nanocomposites and reached a "win-win" cooperation in NIR-induced photodynamic therapy and UCL imaging.