Rare-earth-based upconversion nanotechnology has recently shown great promise for photodynamic therapy (PDT). However, the NIR-induced PDT is greatly restricted by overheating issues on normal bodies and low yields of reactive oxygen species (ROS, O). Here, IR-808-sensitized upconversion nanoparticles (NaGdF:Yb,Er@NaGdF:Nd,Yb) were combined with mesoporous silica, which has Ce6 (red-light-excited photosensitizer) and MC540 (green-light-excited photosensitizer) loaded inside through covalent bond and electrostatic interaction, respectively. When irradiated by tissue-penetrable 808 nm light, the IR-808 greatly absorb 808 nm photons and then emit a broadband peak which overlaps perfectly with the absorption of Nd and Yb. Thereafter, the Nd/Yb incorporated shell synergistically captures the emitted NIR photons to illuminate NaGdF:Yb,Er zone and then radiate ultrabright green and red emissions. The visible emissions simultaneously activate the dual-photosensitizer to produce a large amount of ROS and, importantly, low heating effects. The in vitro and in vivo experiments indicate that the dual-photosensitizer nanostructure has trimodal (UCL/CT/MRI) imaging functions and high anticancer effectiveness, suggesting its potential clinical application as an imaging-guided PDT technique.

The insufficient blood flow and oxygen supply in solid tumor cause hypoxia, which leads to low sensitivity of tumorous cells and thus causing poor treatment outcome. Here, mesoporous manganese dioxide (mMnO 2 ) with ultrasensitive biodegradability in a tumor microenvironment (TME) is grown on upconversion photodynamic nanoparticles for not only TME-enhanced bioimaging and drug release, but also for relieving tumor hypoxia, thereby markedly improving photodynamic therapy (PDT). In this nanoplatform, mesoporous silica coated upconversion nanoparticles (UCNPs@mSiO 2 ) with covalently loaded chlorin e6 are obtained as near-infrared light mediated PDT agents, and then a mMnO 2 shell is grown via a facile ultrasonic way. Because of its unique mesoporous structure, the obtained nanoplatform postmodified with polyethylene glycol can load the chemotherapeutic drug of doxorubicin (DOX). When used for antitumor application, the mMnO 2 degrades rapidly within the TME, releasing Mn 2+ ions, which couple with trimodal (upconversion luminescence, computed tomography (CT), and magnetic resonance imaging) imaging of UCNPs to perform a selfenhanced imaging. Significantly, the degradation of mMnO 2 shell brings an efficient DOX release, and relieve tumor hypoxia by simultaneously inducing decomposition of tumor endogenous H 2 O 2 and reduction of glutathione, thus achieving a highly potent chemo-photodynamic therapy.

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Near infrared (NIR) light triggered phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) affords superior outcome in cancer treatment. However, the reactive oxygen species (ROS) generated by NIR-excited upconversion nanostructure is limited by the feeble upconverted light which cannot activate PDT agents efficiently. Here, an IR-808 dye sensitized upconversion nanoparticle (UCNP) with a chlorin e6 (Ce6)-functionalized silica layer is developed for PDT agent. The two booster effectors (dye-sensitization and core-shell enhancement) synergistically amplify the upconversion efficiency, therefore achieving superbright visible emission under low 808 nm light excitation. The markedly amplified red light subsequently triggers the photosensitizer (Ce6) to produce large amount of ROS for efficient PDT. After the silica is endowed with positive surface, these PDT nanoparticles can be easily grafted on MoS nanosheet. As the optimal laser wavelength of UCNPs is consistent with that of MoS nanosheet for PTT, the invented nanoplatform generates both abundant ROS and local hyperthermia upon a single 808 nm laser irradiation. Both the in vitro and in vivo assays validate that the innovated nanostructure presents excellent cancer cell inhibition effectiveness by taking advantages of the synergistic PTT and PDT, simultaneously, posing trimodal (upconversion luminescence/computed tomography (CT)/magnetic resonance imaging (MRI) imaging capability.