Jiating Xu

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.

In Situ Growth Strategy to Integrate Up-Conversion Nanoparticles with Ultrasmall CuS for Photothermal Theranostics

In the theranostic field, a near-infrared (NIR) laser is located in the optical window, and up-conversion nanoparticles (UCNPs) could be potentially utilized as the imaging agents with high contrast. Meanwhile, copper sulfide (CuS) has been proposed as a photothermal agent with increased temperature under a NIR laser. However, there is still no direct and effective strategy to integrate the hydrophobic UCNPs with CuS until now. Herein, we propose an in situ growth routine based on the hydrophobic core/shell UCNPs combined with ultrasmall water-soluble CuS triggered by single 808 nm NIR irradiation as the theranostic platform. Hydrophobic NaYF4:Yb,Er@NaYF4,Nd,Yb could be turned hydrophilic with highly dispersed and biocompatible properties through conjunction with transferred dopamine. The as-synthesized ultrasmall CuS (3 and 7 nm) served as a stable photothermal agent even after several laser-on/off cycles. Most importantly, comparing with the mix routine, the in situ growth routine to coat UCNPs with CuS is meaningful, and the platform is uniform and stable. Green luminescence-guided hyperthermia could be achieved under a single 808 nm laser, which was evidenced by in vitro and in vivo assays. This nanoplatform is applicable as a bioimaging and photothermal antitumor agent, and the in situ growth routine could be spread to other integration processes.

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.

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.

Bioapplications of graphene constructed functional nanomaterials

Graphene has distinctive mechanical, electronic, and optical properties, which researchers have applied to develop innovative electronic materials including transparent conductors and ultrafast transistors. Lately, the understanding of various chemical properties of graphene has expedited its application in high-performance devices that generate and store energy. Graphene is now increasing its terrain outside electronic and chemical applications toward biomedical areas such as precise bio sensing through graphene-quenched fluorescence, graphene-enhanced cell differentiation and growth, and graphene-assisted laser desorption/ionization for mass spectrometry. In this Account, we evaluate recent efforts to apply graphene and graphene oxides (GO) to biomedical research and a few different approaches to prepare graphene materials designed for biomedical applications and a brief perspective on their future applications. Because of its outstanding aqueous processability, amphiphilicity, surface functionalizability, surface enhanced Raman scattering (SERS), and fluorescence quenching ability, GO chemically exfoliated from oxidized graphite is considered a promising material for biological applications. In addition, the hydrophobicity and flexibility of large-area graphene synthesized by chemical vapor deposition (CVD) allow this material to play an important role in cell growth and differentiation. Graphene is considered to be an encouraging and smart candidate for numerous biomedical applications such as NIR-responsive cancer therapy and fluorescence bio-imaging and drug delivery. To that end, suitable preparation and unique approaches to utilize graphene-based materials such as graphene oxides (GOs), reduced graphene oxides (rGOs), and graphene quantum dots (GQDs) in biology and medical science are gaining growing interest.

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.

UCNPs@gelatin–ZnPc nanocomposite: synthesis, imaging and anticancer properties

To enhance the total emission intensity, particularly the red emission of Yb,Er co-doped nanoparticles for red light activated photodynamic therapy (PDT), we doped Mn2+ ions into the NaGdF4:Yb,Er core, and subsequently coated the NaGdF4:Yb active shell to fabricate core-shell structured, up-conversion nanoparticles of NaGdF4:Yb,Er,Mn@NaGdF4:Yb (abbreviated as UCNPs). A novel and facile encapsulation method with gelatin has been proposed to transfer oleic acid (OA) stabilized UCNPs into an aqueous solution and simultaneously decorate zinc phthalocyanine (ZnPc) photosensitizer molecules. In the encapsulation process, ZnPc molecules are wrapped in the interlaced net structure of the peptide chain from gelatin, forming the UCNPs@gel-ZnPc nanocomposite. The nanoplatform has high emission intensity and excellent biocompatibility, as was expected. More importantly, the enhanced red emission of UCNPs has significant overlap with the UV absorbance of ZnPc; therefore, it can effectively activate the sensitizer to produce a large amount of singlet oxygen reactive oxygen species (ROS, 1O2) to kill cancer cells, which has evidently been verified by the in vitro results. Combined with the inherent up-conversion luminescence (UCL) imaging properties, this UCNPs@gel-ZnPc nanoplatform could have potential application in PDT and imaging fields.

Design, fabrication, luminescence and biomedical applications of UCNPs@mSiO2–ZnPc–CDs–P(NIPAm-MAA) nanocomposites

A nanoplatform capable of pH/thermo-coupling sensitive drug release, multimodal imaging, and synergetic antitumor therapy was designed and prepared. The core-shell structured platform consists of a dominant red up-converted luminescence (UCL) core and a copolymer P(NIPAm-MAA) gated mesoporous silica layer with functional cargos loaded inside. Due to the tri-doped Yb/Ce/Ho ions in the core and the inert shell coating, the nanoparticles show intense red UCL under NIR laser excitation. Thereafter, the emitted red light transfers energy to the conjugated photodynamic therapy (PDT) agent zinc(ii)-phthalocyanine (ZnPc), which produces singlet oxygen, and the decorated carbon dots (CDs) generate an obvious photothermal effect upon 980 nm laser irradiation as well as avoiding ZnPc leakage. Notably, the thermal effect together with the acidic environment in the cancer sites induces the shrinkage of P(NIPAm-MAA), realizing targeted and controllable release of DOX. Due to the photothermal-/photodynamic-/chemo-therapy derived synergistic effect, the nanoplatform exhibits desirable tumor inhibition efficacy, as verified by both in vitro and in vivo results. In particular, the doped rare earth ions enable the product to have simultaneous UCL, magnetic resonance imaging (MRI) and computed tomography (CT) imaging properties, thus achieving the integration of diagnosis and therapy.

A novel core–shell structured upconversion nanorod as a multimodal bioimaging and photothermal ablation agent for cancer theranostics

A multifunctional core-shell nanocomposite based on noble metal plasmons coated with upconversion material has emerged as a promising cancer theranostics nanoplatform that integrates properties such as multimodal imaging, photothermal effects, good biocompatibility, and efficient therapy. However, a reasonable combination of plasmons and upconversion materials, as well as increased penetration depth, has always challenged the anti-cancer efficiency. Here, a unique kind of fluorescent thermal-magnetic resonance core-shell upconversion nanostructure has been designed and fabricated to simultaneously achieve photothermal therapy (PTT) and multimodal imaging. Gold nanorods (GNRs) are used as the plasmon cores and NaGdF4 with rare-earth Yb3+/Er3+ ions co-doping are used as the upconversion luminescence (UCL) shells, merging into upconversion nanorods (UCNRs) of GNRs@NaGdF4:Yb3+,Er3+. An NaGdF4 shell synthesized by a hydrothermal method can substitute for the cetyltrimethylammonium bromide (CTAB) on the surface of GNRs, which offers the benefits of reducing toxicity and increasing biocompatibility. More significantly, the red and green emission of Yb3+/Er3+ couples convert near-infrared (NIR) into visible light, appropriately overlapping with absorbance of GNRs, which improves the photothermal conversion efficiency. Meanwhile, we designed small and low-aspect-ratio GNR cores for the absorption of UCNRs in vivo. Verification with evidence from in vivo and in vitro assays shows that these core-shell UCNRs exhibit a talented potential application in multimodal bioimaging and PTT.

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.