Huiting Bi

Highly Emissive Dye-Sensitized Upconversion Nanostructure for Dual-Photosensitizer Photodynamic Therapy and Bioimaging

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, 1O2). Here, IR-808-sensitized upconversion nanoparticles (NaGdF4:Yb,Er@NaGdF4: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 Nd3+ and Yb3+. Thereafter, the Nd3+/Yb3+ incorporated shell synergistically captures the emitted NIR photons to illuminate NaGdF4: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.

Charge convertibility and near infrared photon co-enhanced cisplatin chemotherapy based on upconversion nanoplatform

Optimal nano-sized drug carrier requires long blood circulation, selective extravasation, and efficient cell uptake. Here we develop a charge-convertible nanoplatform based on Pt(IV) prodrug loaded NaYF4:Yb,Tm upconversion nanoparticles (UCNs), followed by coating a layer of PEG-PAH-DMMA polymer (UCNs-Pt(IV)@PEG-PAH-DMMA). The polymer endows the platform with high biocompatibility, initial nano-size for prolonged blood circulation and selective extravasation. Especially, the anionic polymer can response to the mild acidic stimulus (pH ∼6.5) of tumor extracellular microenvironment and experience charge-shifting to a cationic polymer, resulting in electrostatic repulsion and releases of positive UCNs-Pt(IV). The positive UCNs-Pt(IV) nanoparticles have high affinity to negative cell membrane, leading to efficacious cell internalization. Simultaneously, the ultraviolet (UV) light emitted from UCNs upon near-infrared (NIR) light irradiation, together with the reductive glutathione (GSH) in cancer cells efficiently activate the Pt(IV) prodrug to highly cytotoxic Pt(II), realizing NIR photon improved chemotherapy. The experimental results reveal the charge convertibility, low adverse effect and markedly enhanced tumor ablation efficacy upon NIR laser irradiation of this smart nanoplatform. Moreover, combining the inherent upconversion luminescence (UCL) and computed tomography (CT) imaging capabilities, an alliance of cancer diagnosis and therapy has been achieved.

Uniformly Dispersed ZnFe 2 O 4 Nanoparticles on Nitrogen-Modified Graphene for High-Performance Supercapacitor as Electrode

A facile strategy has been adopted for the preparation of ZnFe2O4/NRG composite by anchoring ultrasmall ZnFe2O4 nanoparticles on nitrogen-doped reduced graphene (denoted as NRG) for high-performance supercapacitor electrode. Remarkably, the growth of ZnFe2O4 nanocrystals, the reduction of graphitic oxide and the doping of nitrogen to graphene have been simultaneously achieved in one process. It is found that the NRG employed as substrate can not only control the formation of nano-sized ZnFe2O4, but also guarantee the high dispersion without any agglomeration. Benefiting from this novel combination and construction, the hybrid material has large surface area which can provide high exposure of active sites for easy access of electrolyte and fast electron transport. When served as supercapacitor electrode, the ZnFe2O4/NRG composite exhibits a favorable specific capacitance of 244 F/g at 0.5 A/g within the potential range from −1 to 0 V, desirable rate stability (retain 131.5 F/g at 10 A/g) and an admirable cycling durability of 83.8% at a scan rate of 100 mV/s after 5000 cycles. When employed as symmetric supercapacitor, the device demonstrates favorable performance. These satisfactory properties of the ZnFe2O4/NRG composite can make it be of great promise in the supercapacitor application.

808 nm near-infrared light controlled dual-drug release and cancer therapy in vivo by upconversion mesoporous silica nanostructures

The design of stimuli-responsive drug delivery systems has attracted much attention to improve therapeutic efficacy for clinical applications. Here an 808 nm NIR light responsive dual-drug system was designed for cancer treatment both in vitro and in vivo. Mesoporous silica coated NaYF4:Yb0.4/Tm0.02@NaGdF4:Yb0.1@NaNdF4:Yb0.1 (UCNPs) with a core-shell structure (labeled as UCNPs@mSiO2) was prepared and loaded with the antitumor drug doxorubicin (DOX). The surface of the composite was functionalized with β-cyclodextrin rings bridged by the light cleavable platinum(iv) pro-drug, thus blocking DOX inside the mesopores of silica. When excited by 808 nm NIR light, the emitted UV light from the UCNPs was used to activate the platinum(iv) pro-drug to gain higher toxicity platinum(ii) complexes and open the mesopores of silica (at the same time) to release DOX molecules. Both DOX and platinum(ii) complexes can kill cancer cells. This dual-drug delivery system may represent a new avenue for the application of UCNPs in photoactivated cancer therapy.

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.

Ni(OH) 2 nanosheets grown on porous hybrid g-C 3 N 4 /RGO network as high performance supercapacitor electrode

A porous hybrid g-C3N4/RGO (CNRG) material has been fabricated through a facile hydrothermal process with the help of glucose molecules, and serves as an efficient immobilization substrate to support ultrathin Ni(OH)2 nanosheets under an easy precipitation process. It was found that the g-C3N4 flakes can uniformly coat on both sides of the RGO, forming sandwich-type composites with a hierarchical structure. It is worth noting that the introduction of the g-C3N4 can effectively achieve the high dispersion and avoid the agglomeration of the nickel hydroxide, and significantly enhance the synthetically capacitive performance. Owning to this unique combination and structure, the CNRG/Ni(OH)2 composite possesses large surface area with suitable pore size distribution, which can effectively accommodate the electrolyte ions migration and accelerate efficient electron transport. When used as electrode for supercapacitor, the hybrid material exhibits high supercapacitive performance, such as an admirable specific capacitance (1785 F/g at a current density of 2 A/g), desirable rate stability (retain 910 F/g at 20 A/g) and favorable cycling durability (maintaining 71.3% capacity after 5000 cycles at 3 A/g). Such desirable properties signify that the CNRG/Ni(OH)2 composites can be a promising electrode material in the application of the supercapacitor.

CuS–Pt(IV)–PEG–FA nanoparticles for targeted photothermal and chemotherapy

Platinum (Pt)(iv) pro-drugs, which can be reduced to highly cytotoxic Pt(ii) by high concentrations of glutathione (GSH) in cancer cells, offer a new approach to defense against tumors. A carrier with controlled release and targeted functions is essential to determine its final anticancer efficiency. In this study, we report a targeted drug delivery system by fabricating CuS-Pt(iv)-PEG-FA nanoparticles (CuS-Pt(iv) NPs) that integrates Pt drug-induced chemotherapy and CuS nanoparticles-mediated photothermal therapy (PTT) under near infrared (NIR) light irradiation. The attached PEG and folic acid (FA) molecules endow the system with high biocompatibility and targeted property. The release of Pt was up to 84.4% in the presence of GSH in the tumor cells due to the reduction property of GSH. Combined with the photothermal effect with high photothermal conversion efficiency (32.1%) upon NIR light irradiation, a remarkable tumor inhabitation efficacy was been achieved. The in vitro assay manifested that CuS-Pt(iv) NPs can kill more cancer cells than that of DSP and cisplatin; the in vivo results indicate that the group treated with intravenous injection of CuS-Pt(iv) NPs exhibits excellent antitumor effects upon NIR light irradiation.

Glutathione Mediated Size‐Tunable UCNPs‐Pt(IV)‐ZnFe2O4 Nanocomposite for Multiple Bioimaging Guided Synergetic Therapy

Here a multifunctional nanoplatform (upconversion nanoparticles (UCNPs)-platinum(IV) (Pt(IV))-ZnFe2 O4 , denoted as UCPZ) is designed for collaborative cancer treatment, including photodynamic therapy (PDT), chemotherapy, and Fenton reaction. In the system, the UCNPs triggered by near-infrared light can convert low energy photons to high energy ones, which act as the UV-vis source to simultaneously mediate the PDT effect and Fentons reaction of ZnFe2 O4 nanoparticles. Meanwhile, the Pt(IV) prodrugs can be reduced to high virulent Pt(II) by glutathione in the cancer cells, which can bond to DNA and inhibit the copy of DNA. The synergistic therapeutic effect is verified in vitro and in vivo results. The cleavage of Pt(IV) from UCNPs during the reduction process can shift the larger UCPZ nanoparticles (NPs) to the smaller ones, which promotes the enhanced permeability and retention (EPR) and deep tumor penetration. In addition, due to the inherent upconversion luminescence (UCL) and the doped Yb3+ and Fe3+ in UCPZ, this system can serve as a multimodality bioimaging contrast agent, covering UCL, X-ray computed tomography, magnetic resonance imaging, and photoacoustic. A smart all-in-one imaging-guided diagnosis and treatment system is realized, which should have a potential value in the treatment of tumor.

A novel strategy for markedly enhancing the red upconversion emission in Er3+/Tm3+ cooperated nanoparticles

A rare-earth-based upconversion nanocrystal that exhibits anti-Stokes nature has attracted worldwide attention due to its unique physical properties. In this work, a novel core–active shell upconversion nanocrystal (NaErF4:Tm@NaGdF4:Yb) which emits super-bright red emission upon 980 nm near-infrared (NIR) laser excitation is presented. The Er3+ ions act as both sensitizers and activators to enable an efficient upconversion process of core nanocrystals. To mitigate the luminescence quenching caused by the energy migration between the Er3+ ions and internal lattice defects, an energy trapping center of Tm3+ was introduced into the core to confine the energy of Er3+ through an energy back transfer (Er3+ → Tm3+ → Er3+) pathway. After that, an active shell of NaGdF4:Yb was grown on the core zone to simultaneously enable the efficient energy transfer from NIR photons to the upconverting zone and suppress the luminescence quenching caused by surface defects and surface associated ligands. It is worth noting that both the Tm3+ and active shell can enhance the red to green (R/G) ratio of the Er3+ emission, thus resulting in an ultra-bright red emission with high purity. The core–active shell nanoparticles possess more intense (∼20 times higher) emission intensity than core–inert shell nanoparticles (NaErF4:Tm@NaGdF4), and their quantum yield reaches as high as 3.71%. This finding paves a convenient way to obtain red-emissive upconversion nanocrystals with high purity for special applications.

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.