Showing papers by "Zhuang Liu published in 2014"

Drug Delivery with PEGylated MoS2 Nano‐sheets for Combined Photothermal and Chemotherapy of Cancer

Abstract: MoS2 nanosheets functionalized with poly-ethylene glycol are for the first time used as a multifunctional drug delivery system with high drug loading capacities. Using doxorubicin as the model drug and taking advantages of the strong near-infrared absorbance of MoS2, combined photothermal and chemotherapy of cancer is realized in animal experiments, achieving excellent synergistic anti-tumor effect upon systemic administration.

PEGylated WS2 Nanosheets as a Multifunctional Theranostic Agent for in vivo Dual-Modal CT/Photoacoustic Imaging Guided Photothermal Therapy

Abstract: A new generation of photothermal theranostic agents is developed based on PEGylated WS2 nanosheets. Bimodal in vivo CT/photoacoustic imaging reveals strong tumor contrast after either intratumoral or intravenous injection of WS2 -PEG. In vivo photothermal treatment is then conducted in a mouse tumor model, achieving excellent therapeutic efficacy with complete ablation of tumors. This work promises further exploration of transition-metal dichalcogenides for biomedical applications, such as cancer imaging and therapy.

Ultrathin WS2 nanoflakes as a high-performance electrocatalyst for the hydrogen evolution reaction.

Abstract: Much has been done to search for highly efficient and inexpensive electrocatalysts for the hydrogen evolution reaction (HER), which is critical to a range of electrochemical and photoelectrochemical processes. A new, high-temperature solution-phase method for the synthesis of ultrathin WS2 nanoflakes is now reported. The resulting product possesses monolayer thickness with dimensions in the nanometer range and abundant edges. These favorable structural features render the WS2 nanoflakes highly active and durable catalysts for the HER in acids. The catalyst exhibits a small HER overpotential of approximately 100 mV and a Tafel slope of 48 mV/decade. These ultrathin WS2 nanoflakes represent an attractive alternative to the precious platinum benchmark catalyst and rival MoS2 materials that have recently been heavily scrutinized for the electrocatalytic HER.

Immunological Responses Triggered by Photothermal Therapy with Carbon Nanotubes in Combination with Anti-CTLA-4 Therapy to Inhibit Cancer Metastasis

Abstract: Photothermal ablation of primary tumors with single-walled carbon nanotubes is demonstrated to be able to trigger significant adaptive immune responses, which are not observed if tumors are removed by surgical resection. Such a treatment in combination with anti-CTLA-4 antibody therapy is able to prevent the development of tumor metastasis, which is a major cause of cancer death.

Tumor metastasis inhibition by imaging-guided photothermal therapy with single-walled carbon nanotubes.

Abstract: Multi-modal imaging guided photothermal therapy with single-walled carbon nanotubes affords effective destruction of primary tumors together with cancer cells in sentinel lymph nodes. This results in remarkably prolonged mouse survival compared to mice treated by elimination of only the primary tumor by either surgery or conventional photothermal therapy.

Efficient planar heterojunction perovskite solar cells employing graphene oxide as hole conductor

Abstract: Graphene oxide (GO) is employed as a hole conductor in inverted planar heterojunction perovskite solar cells, and the devices with CH3NH3PbI3−xClx as absorber achieve an efficiency of over 12%. The perovskite film grown on GO exhibits enhanced crystallization, high surface coverage ratio as well as preferred in-plane orientation of the (110) plane. Efficient hole extraction from the perovskite to GO is demonstrated.

Combined photothermal and photodynamic therapy delivered by PEGylated MoS2 nanosheets.

Abstract: Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2-PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment.

Engineering of Multifunctional Nano-Micelles for Combined Photothermal and Photodynamic Therapy Under the Guidance of Multimodal Imaging

Abstract: The integration of diagnostic and therapeutic functionalities on a single theranostic nano-system holds great promise to enhance the accuracy of diagnosis and improve the efficacy of therapy. Herein, a multifunctional polymeric nano-micelle system that contains a photosensitizer chlorin e6 (Ce6) is successfully fabricated, at the same time serving as a chelating agent for Gd3+, together with a near-infrared (NIR) dye, IR825. With a r1 relativity 7 times higher than that of the commercial agent Magnevist, strong fluorescence offered by Ce6, and high NIR absorbance attributed to IR825, these theranostic micelles can be utilized as a contrast agent for triple modal magnetic resonance (MR), fluorescence, and photoacoustic imaging of tumors in a mouse model. The combined photothermal and photodynamic therapy is then carried out, achieving a synergistic anti-tumor effect both in vitro and in vivo. Different from single photo treatment modalities which only affect the superficial region of the tumor under mild doses, the combination therapy at the same dose using this agent is able to induce significant damage to both superficial and deep parts of the tumor. Therefore, this work presents a polymer based theranostic platform with great potential in multimodal imaging and combination therapy of cancer.

Amplifying the Red-Emission of Upconverting Nanoparticles for Biocompatible Clinically Used Prodrug-Induced Photodynamic Therapy

Abstract: A class of biocompatible upconverting nanoparticles (UCNPs) with largely amplified red-emissions was developed. The optimal UCNP shows a high absolute upconversion quantum yield of 3.2% in red-emission, which is 15-fold stronger than the known optimal β-phase core/shell UCNPs. When conjugated to aminolevulinic acid, a clinically used photodynamic therapy (PDT) prodrug, significant PDT effect in tumor was demonstrated in a deep-tissue (>1.2 cm) setting in vivo at a biocompatible laser power density. Furthermore, we show that our UCNP–PDT system with NIR irradiation outperforms clinically used red light irradiation in a deep tumor setting in vivo. This study marks a major step forward in photodynamic therapy utilizing UCNPs to effectively access deep-set tumors. It also provides an opportunity for the wide application of upconverting red radiation in photonics and biophotonics.

Ultra-Small Iron Oxide Doped Polypyrrole Nanoparticles for In Vivo Multimodal Imaging Guided Photothermal Therapy

Abstract: National Natural Science Foundation of China [51222203, 51002100, 51132006]; National "973" Program of China [2012CB932601, 2013CB932702, 2011CB911002]; Priority Academic Program Development of Jiangsu Higher Education Institutions; Post-doctoral research program of Jiangsu Province [1202044C]

Multifunctional Theranostic Red Blood Cells For Magnetic‐Field‐Enhanced in vivo Combination Therapy of Cancer

Abstract: Red blood cells are attached to iron oxide nanoparticles pre-coated with chlorine e6, a photosensitizer, and then loaded with a chemotherapeutic drug, doxorubicin, to enable imaging-guided combined photodynamic and chemotherapy of cancer, achieving excellent synergistic therapeutic effects in an animal tumor model. This work highlights the great promise of integrating cell-based drug-delivery systems with nanotechnology as a biocompatible multifunctional platform for applications in cancer theranostics.

Photosensitizer Loaded Nano-Graphene for Multimodality Imaging Guided Tumor Photodynamic Therapy

Abstract: Graphene, a 2-dimensional carbon nanomaterial, has attracted wide attention in biomedical applications, owing to its intrinsic physical and chemical properties. In this work, a photosensitizer molecule, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH or Photochlor®), is loaded onto polyethylene glycol (PEG)-functionalized graphene oxide (GO) via supramolecular π-π stacking. The obtained GO-PEG-HPPH complex shows high HPPH loading efficiency. The in vivo distribution and delivery were tracked by fluorescence imaging as well as positron emission tomography (PET) after radiolabeling of HPPH with 64Cu. Compared with free HPPH, GO-PEG-HPPH offers dramatically improved photodynamic cancer cell killing efficacy due to the increased tumor delivery of HPPH. Our study identifies a role for graphene as a carrier of PDT agents to improve PDT efficacy and increase long-term survival following treatment.

Surface Coating‐Dependent Cytotoxicity and Degradation of Graphene Derivatives: Towards the Design of Non‐Toxic, Degradable Nano‐Graphene

Abstract: With the increasing interests of using graphene and its derivatives in the area of biomedicine, the systematic evaluation of their potential risks and impacts to biological systems is becoming critically important. In this work, we carefully study how surface coatings affect the cytotoxicity and extracellular biodegradation behaviors of graphene oxide (GO) and its derivatives. Although naked GO could induce significant toxicity to macrophages, coating those two-dimensional nanomaterials with biocompatible macromolecules such as polyethylene glycol (PEG) or bovine serum albumin (BSA) could greatly attenuate their toxicity, as independently evidenced by several different assay approaches. On the other hand, although GO can be gradually degraded through enzyme induced oxidization by horseradish peroxidase (HRP), both PEG and BSA coated GO or reduced GO (RGO) are rather resistant to HRP-induced biodegradation. In order to obtain biocompatible functionalized GO that can still undergo enzymatic degradation, we conjugate PEG to GO via a cleavable disulfide bond, obtaining GO-SS-PEG with negligible toxicity and considerable degradability, promising for further biomedical applications.

Graphene-based nanocomposite as an effective, multifunctional, and recyclable antibacterial agent.

Abstract: The development of new antibacterial agents that are highly effective are of great interest. Herein, we present a recyclable and synergistic nanocomposite by growing both iron oxide nanoparticles (IONPs) and silver nanoparticles (AgNPs) on the surface of graphene oxide (GO), obtaining GO-IONP-Ag nanocomposite as a novel multifunctional antibacterial material. Compared with AgNPs, which have been widely used as antibacterial agents, our GO-IONP-Ag shows much higher antibacterial efficiency toward both Gram-negative bacteria Escherichia coli (E. coli) and Gram-positive bacteria Staphylococcus aureus (S. aureus). Taking the advantage of its strong near-infrared (NIR) absorbance, photothermal treatment is also conducted with GO-IONP-Ag, achieving a remarkable synergistic antibacterial effect to inhibit S. aureus at a rather low concentration of this agent. Moreover, with magnetic IONPs existing in the composite, we can easily recycle GO-IONP-Ag by magnetic separation, allowing its repeated use. Given the abov...

Smart pH-responsive nanocarriers based on nano-graphene oxide for combined chemo- and photothermal therapy overcoming drug resistance

Abstract: A pH-responsive nanocarrier is developed by coating nanoscale graphene oxide (NGO) with dual types of polymers, polyethylene glycol (PEG) and poly(allylamine hydrochloride) (PAH), the latter of which is then modified with 2,3-dimethylmaleic anhydride (DA) to acquire pH-dependent charge reversibility. After loading with doxorubicin (DOX), a chemotherapy drug, the obtained NGO-PEG-DA/DOX complex exhibits a dual pH-responsiveness, showing markedly enhanced cellular uptake under the tumor microenvironmental pH, and accelerated DOX release under a further lowered pH inside cell lysosomes. Combining such a unique behavior with subsequently slow efflux of DOX, NGO-PEG-DA/DOX offers remarkably improved cell killing for drug-resistant cancer cells under the tumor microenvironmental pH in comparison with free DOX. Exploiting its excellent photothermal conversion ability, combined chemo- and photothermal therapy is further demonstrated using NGO-PEG-DA/DOX, realizing a synergistic therapeutic effect. This work presents a novel design of surface chemistry on NGO for the development of smart drug delivery systems responding to the tumor microenvironment and external physical stimulus, with the potential to overcome drug resistance.

Photoacoustic Imaging Guided Near-Infrared Photothermal Therapy Using Highly Water-Dispersible Single-Walled Carbon Nanohorns as Theranostic Agents

Abstract: The poly(maleic anhydride-alt-1-octadecene-poly(ethylene glycol)) (C18PMH-PEG) modified single-walled carbon nanohorns (SWNHs) are designed with high stability and biocompatibility. The as-prepared SWNHs/C18PMH-PEG not only can serve as an excellent photothermal agent but also can be used as a promising photoacoustic imaging (PAI) agent both in vitro and in vivo due to its strong absorption in the near infrared (NIR) region. The PAI result reveals that the SWNHs/C18PMH-PEG possesses ultra long blood circulation time and can significantly be accumulated at the tumor site through the enhanced penetration and retention (EPR) effect. The maximum accumulation of SWNHs/C18PMH-PEG at tumor site could be achieved at the time point of 24 h after intravenous injection, which is considered to be the optimal time for the 808 nm laser treatment. The subsequent photothermal ablation of tumors can be achieved without triggering any side effects. Therefore, a PAI guided PTT platform based on SWNHs is proposed and highlights the potential theranostic application for biomedical uses.

Visualization of Protease Activity In Vivo Using an Activatable Photo-Acoustic Imaging Probe Based on CuS Nanoparticles

Abstract: Herein, we for the first time report a novel activatable photoacoustic (PA) imaging nano-probe for in vivo detection of cancer-related matrix metalloproteinases (MMPs). A black hole quencher 3 (BHQ3) which absorbs red light is conjugated to near-infrared (NIR)-absorbing copper sulfide (CuS) nanoparticles via a MMP-cleavable peptide linker. The obtained CuS-peptide-BHQ3 (CPQ) nano-probe exhibits two distinctive absorption peaks at 630 nm and 930 nm. Inside the tumor microenviorment where MMPs present, the MMP-sensitive peptide would be cleaved, releasing BHQ3 from the CuS nanoparticles, the former of which as a small molecule is then rapidly cleared out from the tumor, whereas the latter of which as large nanoparticles would retain inside the tumor for a much longer period of time. As the result, the PA signal at 680 nm which is contributed by BHQ3 would be quickly diminished while that at 930 nm would be largely retained. The PA signal ratio of 680 nm / 930 nm could thus serve as an in vivo indicator of MMPs activity inside the tumor. Our work presents a novel strategy of in vivo sensing of MMPs based on PA imaging, which should offer remarkably improved detection depth compared with traditional optical imaging techniques.

Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing

Abstract: Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer.

Synthesis of Au–Fe3O4 heterostructured nanoparticles for in vivo computed tomography and magnetic resonance dual model imaging

Abstract: Water-soluble Au-Fe3O4 heterostructured nanoparticles with high biocompatibility were synthesized and applied as a dual modality contrast agent. These nanoparticles present strong CT/MRI contrast enhancement in a rabbit model. Low concentrations of Au-Fe3O4 were found to obtain a similar effect to high concentrations of a commercial iodine agent in the CT image.

Magnetic Targeting Enhanced Theranostic Strategy Based on Multimodal Imaging for Selective Ablation of Cancer

Abstract: The booming development of nanomedicine offers great opportunities for cancer diagnostics and therapeutics. Herein, a magnetic targeting-enhanced cancer theranostic strategy using a multifunctional magnetic-plasmonic nano-agent is developed, and a highly effective in vivo tumor photothermal therapy, which is carefully planed based on magnetic resonance (MR)/photoacoustic (PA) multimodal imaging, is realized. By applying an external magnetic field (MF) focused on the targeted tumor, a magnetic targeting mediated enhanced permeability and retention (MT-EPR) effect is observed. While MR scanning provides tumor localization and reveals time-dependent tumor homing of nanoparticles for therapeutic planning, photoacoustic imaging with higher spatial resolution allows noninvasive fine tumor margin delineation and vivid visualization of three dimensional distributions of theranostic nanoparticles inside the tumor. Utilizing the near-infrared (NIR) plasmonic absorbance of those nanoparticles, selective photothermal tumor ablation, whose efficacy is predicted by real-time infrared thermal imaging intra-therapeutically, is carried out and then monitored by MR imaging for post-treatment prognosis. Overall, this study illustrates the concept of imaging-guided MF-targeted photothermal therapy based on a multifunctional nano-agent, aiming at optimizing therapeutic planning to achieve the most efficient cancer therapy.

J-Aggregates of Organic Dye Molecules Complexed with Iron Oxide Nanoparticles for Imaging-Guided Photothermal Therapy Under 915-nm Light

Abstract: Recently, the development of nano-theranostic agents aiming at imaging guided therapy has received great attention. In this work, a near-infrared (NIR) heptamethine indocyanine dye, IR825, in the presence of cationic polymer, polyallylamine hydrochloride (PAH), forms J-aggregates with red-shifted and significantly enhanced absorbance. After further complexing with ultra-small iron oxide nanoparticles (IONPs) and the followed functionalization with polyethylene glycol (PEG), the obtained IR825@PAH-IONP-PEG composite nanoparticles are highly stable in different physiological media. With a sharp absorbance peak, IR825@PAH-IONP-PEG can serve as an effective photothermal agent under laser irradiation at 915 nm, which appears to be optimal in photothermal therapy application considering its improved tissue penetration compared with 808-nm light and much lower water heating in comparison to 980-nm light. As revealed by magnetic resonance (MR) imaging, those nanoparticles after intravenous injection exhibit high tumor accumulation, which is then harnessed for in vivo photothermal ablation of tumors, achieving excellent therapeutic efficacy in a mouse tumor model. This study demonstrates for the first time that J-aggregates of organic dye molecules are an interesting class of photothermal material, which when combined with other imageable nanoprobes could serve as a theranostic agent for imaging-guided photothermal therapy of cancer.

Dual-aptamer modification generates a unique interface for highly sensitive and specific electrochemical detection of tumor cells.

Abstract: Because circulating tumor cells (CTCs) have been proven to be an important clue of the tumor metastasis, their detection thus plays a pivotal role in the diagnosis and prognosis of cancer. Herein, we fabricate an electrochemical sensor by directly conjugating two cell-specific aptamers, TLS1c and TLS11a, which specifically recognize MEAR cancer cells, to the surface of a glassy carbon electrode (GCE) via the formation of amide bonds. The two aptamers are simultaneously conjugated to the GCE surface via precisely controlled linkers: TLS1c through a flexible linker (a single-stranded DNA T15; ss-TLS1c) and TLS11a through a rigid linker (a double-stranded DNA T15/A15; ds-TLS11a). It is found that such ss-TLS1c/ds-TLS11a dual-modified GCEs show greatly improved sensitivity in comparison with those modified with a single type of aptamer alone or ds-TLS1c/ds-TLS11a with both rigid linkers, suggesting that our optimized, rationally designed electrode–aptamer biosensing interface may enable better recognition and...