Intelligent Fe-Mn Layered Double Hydroxides Nanosheets Anchored with Upconversion Nanoparticles for Oxygen-Elevated Synergetic Therapy and Bioimaging.

Multimodal synergistic therapy based on photodynamic therapy (PDT), photothermal therapy (PTT), and chemodynamic therapy (CDT) has attracted increasing attention in cancer therapy. However, the scant therapeutic efficiency is always a barrier for further application. Herein, a smart tumor microenvironment (TME) responsive nanocatalysts are developed by adopting Fe-Mn layered double hydroxides (FeMn-LDH) as an effective photothermal nanocarrier to load mesoporous silica and chlorin e6 (Ce6)-covalently coated upconversion nanoparticles (UCSP) for multimodal imaging for directed therapy. Under acidic TME, FeMn-LDH degrades into Fe3+ and Mn2+ ions to initiate a Fenton-like reaction inducing CDT and enhancing magnetic resonance imaging. Additionally, Fe3+ can decompose H2 O2 to oxygen (O2 ), enhancing PDT guided by UCSP. As a representative noninvasive imaging probe, the upconversion luminescence will recover after decomposition of FeMn-LDH, and provide high-resolution upconversion luminescent imaging guidance for pinpointed PDT. Moreover, the photothermal properties of FeMn-LDH can further enhance CDT effects. The synergistic therapy and multifunctional imaging can realize the integration of diagnosis and treatment.

Quad-Model Imaging-Guided High-Efficiency Phototherapy Based on Upconversion Nanoparticles and ZnFe2O4 Integrated Graphene Oxide.

The strategy of diagnosis-to-therapy to realize the integration of imaging and high antitumor efficiency has become the most promising method. Light-induced therapeutic technologies have drawn considerable interest. However, the limited penetration depth of UV/vis excitation and relatively low efficiency are the main obstacles for its further clinic application. For this concern, we presented a facile method to anchor ultrasmall ZnFe2O4 nanoparticles and upconversion luminescence nanoparticles (UCNPs) on graphene oxide (GO) nanosheets (GO/ZnFe2O4/UCNPs, abbreviated as GZUC). To solve the penetration question, here we introduced Tm3+-doped UCNPs to convert the high-penetrated near-infrared (NIR) light into UV/vis photons to activate the photodynamic process. In this system, the dual phototherapy from GO and ZnFe2O4 has been realized upon NIR laser irradiation. Combined with the photodynamic therapy (PDT) based on Fenton reaction that ZnFe2O4 nanoparticles react with excessive H2O2 in tumor microenvironment to produce toxic hydroxyl radicals (·OH), an excellent anticancer efficiency has been achieved. Furthermore, 4-fold imaging including upconversion luminescence (UCL), computed tomography (CT), magnetic resonance imaging (MRI) and photoacoustic tomography (PAT) has been obtained due to its intrinsic properties, thereby successfully realizing diagnosis-monitored therapy. Our demonstration provided a feasible strategy to solve the main problems in current light-triggered theranostic.

Redox-responsive UCNPs-DPA conjugated NGO-PEG-BPEI-DOX for imaging-guided PTT and chemotherapy for cancer treatment.

The disulfide bond (-S-S-) is an enormously valuable functional group in a variety of chemical and biological agents that display effective reactivity or biological activities (e.g., antitumor activities). The disulfide bonds prevalent in proteins are somewhat oxidizing in the extracellular space; however, such disulfide bonds can rarely be found inside cells because of disulfide cleavage reactions facilitated by abundant free cellular thiols, including glutathione (GSH), which is the most important common thiol-containing small molecule. Interestingly, intracellular GSH concentrations are considerably higher in cancer cells than in analogous normal cells; this feature may prove to be significant in the development of anticancer drug delivery systems (DDS). Moreover, upconversion nanoparticles (UCNPs) have been extensively investigated in multimodal imaging, photodynamic therapy (PDT) and photothermal therapy. UCNPs exploit near-infrared excitation instead of ultraviolet excitation and possess exclusive properties, which include greatly increased penetration depth in biological samples and reductions in background autofluorescence, photobleaching and photodamage to biological specimens. These fascinating optical features of UCNPs may broaden their prospects in the fields of imaging and therapy. Graphene has emerged as a flat monolayer of carbon atoms that are tightly embedded in a two-dimensional (2D) honeycomb lattice. Widespread research has been carried out on graphene in recent years owing to its exclusive shape and size, as well as innumerable fascinating physical and chemical properties. Owing to their high optical absorption in the near-infrared (NIR) region, graphene and GO have been extensively employed for photothermal therapy (PTT). In this study, we attempted to merge the properties of these compounds by conjugating UCNPs and NGO-PEG-BPEI-DOX into a single platform for chemotherapy and photothermal therapy.

Polypyrrole-coated UCNPs@mSiO2@ZnO nanocomposite for combined photodynamic and photothermal therapy.

Designing multifunctional nanoplatforms for the purpose of simultaneous theranostic modalities is critical to address the challenges of cancer therapy. Also, single modalities of phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), cannot meet the requirements of highly efficient treatment. Here, a core-shell-shell nanostructure consisting of a core of upconversion nanoparticles (UCNPs), a layer of mesoporous silica with anchored ZnO nanodots, and an outer layer of polypyrrole (PPy) was developed. In the proposed construct, the emitted ultraviolet (UV) light from the UCNPs core upon 980 nm near-infrared light irradiation can trigger the ZnO nanodots to activate ambient O2 molecules around cancerous tissues to produce toxic reactive oxygen species (ROS), realizing the PDT function. On the other hand, the coated PPy layer can concurrently give rise to an obvious heat effect upon NIR light illumination, thus achieving synergistic PDT and PTT effects; this results in excellent anti-tumor efficiency in vitro and in vivo. Furthermore, in hand with the upconversion luminescence (UCL) and computed tomography (CT) imaging derived from the UCNPs core, dual-mode imaging directed cancer therapy has been realized.

Dopamine-mediated photothermal theranostics combined with up-conversion platform under near infrared light.

An organic-inorganic hybrid core-shell nanostructure, based on mesoporous silica coated upconversion core-shell nanoparticles (NaGdF4:Yb,Er@NaGdF4:Yb@mSiO2-Dopa abbreviated here as UCNP@mSiO2-Dopa) that stably incorporates dopamine (Dopa) in the silica layer was introduced as a theranostic nanoplatform for optical imaging guided photothermal therapy (PTT) using NIR excitation. Silica-attaching polyethylenimine make the Dopa transforms into an active form (transferred Dopa) that strongly absorbs light under single 980 nm irradiation. We show that the activated UCNP@mSiO2-Dopa nanoplatform is able to produce a pronounced photothermal effect, that elevates water temperature from room temperature to 41.8 °C within 2 minutes, while concurrently emitting strong upconverted luminescence (UCL) for visualized guidance under 980 nm laser. In addition, we demonstrate the application of the same UCNP@mSiO2-Dopa nanoplatform for magnetic resonance imaging (MRI) and x-ray computed tomography (CT) enabled by the gadolinium (Gd) element contained in the UCNP. Importantly, the in vitro and in vivo anti-cancer therapeutic effects have been shown efficacious, implying the use of the described nanoplatform as an effective multi-modal imaging enabled PTT agent. Results from the in vivo biodistribution of UCNPs@mSiO2, cellular live/dead assay, and histologic analysis of main organs of treated mice, reveal that the UCNP@mSiO2-Dopa agents are bio-compatible with low toxicity.

Integration of IR-808 Sensitized Upconversion Nanostructure and MoS2 Nanosheet for 808 nm NIR Light Triggered Phototherapy and Bioimaging.

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 MoS2 nanosheet. As the optimal laser wavelength of UCNPs is consistent with that of MoS2 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.