Longfei Tan

Multifunctional gold nanoshells on silica nanorattles: a platform for the combination of photothermal therapy and chemotherapy with low systemic toxicity.

Plasmonic nanomaterials, especially those that can convert near-infrared (NIR) light into heat, have been developed as photothermal agents for localized hyperthermia cancer therapy. After Halas s research group first applied a coating of gold nanoshells on solid silica spheres for tumor ablation, a series of NIR-light-absorbing plasmonic nanomaterials have been fabricated to kill tumorigenic cells without damaging normal cells, such as gold nanorods (GNRs), gold nanocages, AuxAg1 x dendrites, [4] gold nanoshells on polystyrene spheres, assembled gold nanoparticles, and many multifunctional nanocomposites. Based on the attractive photothermal property of these plasmonic nanomaterials to optimize cancer therapy and achieve enhanced antitumor efficacy, the combination of hyperthermia and chemotherapeutic agents is an encouraging approach, which can result in synergistic effects that are greater than the two treatments alone. GNRs were reported as producing heat to augment the toxicity of chemotherapeutic agents. But by simply mixing GNRs and chemotherapeutic agents, the synergistic effects of thermo-chemotherapy are difficult to realize in vivo because co-delivery of chemotherapeutic agents together with precious GNRinduced hyperthermia sources to the target tissues is still challenging. Importantly, even though different multifunctional systems based on NIR-absorbing nanomaterials have been designed, many parameters of these systems were only assessed in vitro in cellular systems, while no in vivo study of the thermo-chemotherapy effect of plasmonic nanomaterials based on gold nanoshells has been carried out. In vivo experiments on an applicable medicine system should be tested with emphasis on the antitumor effect and toxicity evaluation as they move closer to the clinical setting. In the work reported herein, we first explored the ablation of hepatocellular carcinomas both in vivo and in vitro by the combination of photothermal therapy and chemotherapy using a multifunctional gold nanoshell. Unlike the gold nanoshell employed in the study of Halas and co-workers, the gold nanoshell we use consists of a thin gold nanoshell and a monodispersed mesoporous silica nanorattle (SN) core. SNs, synthesized by our new reported method, endow gold nanoshells with many advantages through their unique structure with movable cores and mesoporous shells. They were considered as an intelligent drug-delivery system because of their high thermal, chemical, and mechanical stability, large specific surface volume, controllable mesoporous pores, and good biocompatibility. Their positively charged surface simplifies the gold nanoshell coating process by not requiring a modification step with silane coupling agents (e.g., 3-aminopropyltriethoxysilane) as in other reports. Based on these advantages, gold nanoshells on silica nanorattles (GSNs) have compact gold shells, controlled uniform size, tunable optical property as NIR-light-absorbing agents, and high-payload sustained drug release as a drugdelivery system. In vitro and in vivo studies prove that the synergistic effects of GSNs for the efficacious treatment of hepatocellular carcinomas are better than the chemotherapy or photothermal therapy alone. Systematic toxicity study indicates the good biocompatibility of this kind of multifunctional gold nanoshell. Additionally, organic dye molecules can be conjugated on the gold nanoshell for imaging, thus rendering the obtained GSNs an all-in-one processing system for photothermal therapy, drug delivery, and cell imaging with low systemic toxicity. Figure 1a shows the structure of SNs synthesized by our previous method. A drug-loaded structure comprising a PEGylated (PEG = polyethylene glycol) gold nanoshell on silica nanorattle spheres (termed pGSNs) is shown in Figure 1b. The products obtained after each synthetic step are shown in Figure 1c–f. SNs have a narrow size distribution with a hydrodynamic diameter of 120 nm (see Figure 1c, and Figure S1 and Table S1 in the Supporting Information) and a positively charged surface at about 36.5 eV (Figure S2 in the Supporting Information). X-ray photoelectron spectroscopy (XPS) proves the existence of free amino groups on the SNs surface (Figure 1g). By simply stirring for 2 hours, gold seed [*] Dr. H. Liu, Dr. L. Li, Dr. T. Liu, L. Tan, X. Wu, Prof. F. Tang Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry Chinese Academy of Sciences Beijing 100190 (P. R. China) Fax: (+ 86)108-254-3521 E-mail: tangfq@mail.ipc.ac.cn Homepage: http://nanocontrol.ipc.ac.cn

Plasmonic Copper Sulfide Nanocrystals Exhibiting Near-Infrared Photothermal and Photodynamic Therapeutic Effects

Recently, plasmonic copper sulfide (Cu2-xS) nanocrystals (NCs) have attracted much attention as materials for photothermal therapy (PTT). Previous reports have correlated photoinduced cell death to the photothermal heat mechanism of these NCs, and no evidence of their photodynamic properties has been reported yet. Herein we have prepared physiologically stable near-infrared (NIR) plasmonic copper sulfide NCs and analyzed their photothermal and photodynamic properties, including therapeutic potential in cultured melanoma cells and a murine melanoma model. Interestingly, we observe that, besides a high PTT efficacy, these copper sulfide NCs additionally possess intrinsic NIR induced photodynamic activity, whereupon they generate high levels of reactive oxygen species. Furthermore, in vitro and in vivo acute toxic responses of copper sulfide NCs were also elicited. This study highlights a mechanism of NIR light induced cancer therapy, which could pave the way toward more effective nanotherapeutics.

A Silica Nanorattle with a Mesoporous Shell: An Ideal Nanoreactor for the Preparation of Tunable Gold Cores

www.MaterialsViews.com C O M M A Silica Nanorattle with a Mesoporous Shell: An Ideal Nanoreactor for the Preparation of Tunable Gold Cores U N IC By Longfei Tan , Dong Chen , Huiyu Liu , and Fangqiong Tang * A IO N Recently, hollow nanospheres with mesoporous shells and metal cores, so-called yolk-shell or rattle-type nanoparticles, have been paid much attention, owing to their unique optical and electrical properties and great potential in imaging and catalysis applications. [ 1–6 ] One important role of the encapsulation of metal core in mesoporous shell is to hinder the interaction between metal core nanoparticles and keep these active metal cores stable even under hash conditions, while allowing the diffusion of small active molecules in and out of the nanospheres. [ 7 , 8 ]

Targeting Gold Nanoshells on Silica Nanorattles: a Drug Cocktail to Fight Breast Tumors via a Single Irradiation with Near-Infrared Laser Light

One of the current challenges in biomedicine is to develop safe and effective nanomedicines for selective tumor therapy.[1] Recently, near-infrared (NIR) light absorbing plasmonic nanomaterials have attracted intensive attention for their hyperthemia therapy to kill tumorigenic cells without damaging normal cells, such as gold nanorods,[2] gold nanocages,[3] AuxAg1-x dendrites,[4] gold nanoshells on polystyrene spheres,[5] assembled gold nanoparticles[6] and many multifunctional nanocomposites.[7] Our previous study reported a novel material of gold nanoshells on drug-loaded silica nanorattles which can combine the hyperthermia with chemotherapy to optimize cancer therapy whose synergistic effects are greater than the two individual treatments alone.[8] Despite the successful application of many gold-based NIR absorbing materials in cancer therapy, most studies of them rely on the passive targeting effect (the so-called enhanced permeability and retention, EPR effect) to direct nanocarriers at tumor sites through the enhanced permeability of tumor vasculature and the decreased draining efficacy of tumor lymphatics.[9,10] The lack of cell specific interactions may decrease the therapeutic efficacy and thus need a relatively long NIR light irradiation time (30 min in vitro, e.g.),[11] a high NIR laser light irradiation intensity (35 W cm-2 in vitro, e.g.),[12] or repeated injections and NIR laser light irradiations[8] as the previous reports. Furthermore, not all tumors exhibit EPR effect which can enhance the preferential accumulation of nanoparticles in the tumor.[13,14] For clinical applications, a more effective drug delivery strategy should be developed to promote the binding and internalization of nanocarrier through their specific interactions with the receptors expressed on the cell surface of interest.[15]

Doxorubicin loaded silica nanorattles actively seek tumors with improved anti-tumor effects

Silica nanorattles (SNs) have proven to be promising vehicles for drug delivery. In order to further enhance efficacy and minimize adverse effects, active targeted delivery to tumors is necessary. In this work, SNs modified with a tumor specific targeting ligand, folic acid (FA), was used as carrier of doxorubicin (DOX) (DOX-FA-SNs). Drug loading, cytotoxicity and cellular uptake of DOX-FA-SNs in vitro in human cervical carcinoma cells (HeLa cells) were evaluated. DOX-FA-SNs showed a higher cytotoxicity in human cervical carcinoma cells (HeLa cells) than DOX loaded carboxyl (-COOH) and poly(ethylene glycol) (PEG) modified SNs (DOX-COOH-SNs and DOX-PEG-SNs, respectively). However, DOX-FA-SNs showed lower cytotoxicity in folate receptor negative normal mouse fibroblast cells (L929 cells) compared with free DOX. In vivo tumor-targeted fluorescence imaging indicated specific tumor targeting and uptake of FA-SNs in nude mice bearing subcutaneous HeLa cell-derived xenograft tumors. In vivo anti-tumor experiments demonstrated that DOX-FA-SNs (10 mg kg(-1) of DOX) significantly regressed the tumor growth and reduced toxicity compared with free DOX. These results have great significance in developing and optimizing SNs as effective intracellular delivery and specific tumor targeting vehicles.

Biodistribution, excretion, and toxicity of mesoporous silica nanoparticles after oral administration depend on their shape

UNLABELLED Mesoporous silica nanoparticles (MSNs) have been proven to be effective drug carriers for oral delivery. However, little attention has been paid to their in vivo biodistribution and toxicity after oral administration. The effect of particle shape on their in vivo behavior is also unknown. In this study, we systematically studied the acute toxicity and biodistribution of three types of MSNs with aspect ratios (ARs) of 1, 1.75 and 5 after oral administration. The effect of particle shape as a key physicochemical parameter of MSNs was discussed. With the increase of AR, MSNs showed decreased in vivo biodegradation, systematic absorption and excretion, especially decreased liver distribution and urinal excretion. During the period of urinal excretion, MSNs induced a shape-dependent renal damage including hemorrhage, vascular congestion and renal tubular necrosis. These findings will enrich the knowledge to rationally engineer bionanomaterials, and bring new insights into nanotoxicity. FROM THE CLINICAL EDITOR Advances in nanotechnology have resulted in improvement in drug delivery, of which mesoporous silica nanoparticles have been used as carriers for oral drugs. Nonetheless, studies on their absorption, distribution, metabolism, excretion (ADME) and toxicity still need to be performed. In this article, authors evaluated the effects of particle size and shape on in vivo behavior. The findings would shine light on future design of future drug delivery systems.

Fabricating Superhydrophilic Wool Fabrics

A simple method for fabricating environmentally stable superhydrophilic wool fabrics is reported here. An ultrathin silica layer coated on the wool altered both the surface roughness and the surface energy of the fiber and endowed the wool fabrics with excellent water absorption. The process of coating silica sols was dependent on an acid solution of low pH, which influenced the electrostatic interactions between nanoparticles and wool fibers. The morphology and composition of silica-sol-coated wool fabrics were characterized by a combination of SEM, TEM, EDX, FTIR, and XPS measurements. The possible mechanism and size effect of silica nanoparticles on the hydrophilic property of wool fabric were discussed. The washing fastness of the superhydrophilic wool fabrics in perchlorethylene and water was also evaluated. This study shows that wool fabrics modified by optical transparence, chemical stability, and nontoxic silica sols are promising in constructing smart textiles.

Solvothermal synthesis of ZnO nanoparticles and anti-infection application in vivo.

Zinc oxide nanoparticles (ZnONPs) have been widely studied as the bacteriostatic reagents. However, synthesis of small ZnO nanoparticles with good monodispersion and stability in aqueous solution is still a challenge. Anti-infection research of ZnONPs used as antibacterial agent in vivo is rare. In this paper, a novel, sustainable, and simple method to synthesize ZnO nanoparticles with good monodispersion in aqueous low-temperature conditions and with a small molecule agent is reported. Inhibition zone test and the minimum inhibitory concentration test were performed to examine the antibacterial activity of ZnONPs against bacteria Staphylococcus aureus and Escherichia coli in vitro. For further application in vivo, low cytotoxicity and low acute toxicity in mice of ZnO were demonstrated. Finally, 4 nm ZnONPs combined with poly(vinyl alcohol) gel was used as antibacterial agent in rodent elytritis model, and significant anti-infection effect was proven. In one word, the present research would shed new light on the designing of antibacterial materials like ZnO with promising application in disinfection.

Facile synthesis of hierarchical MoS2–carbon microspheres as a robust anode for lithium ion batteries

Molybdenum disulfide (MoS2) may be a promising alternative for lithium ion batteries (LIBs) because it offers a unique layered crystal structure with a large and tunable distance between layers. This enables the anticipated excellent rate and cycling stability because they can promote the reversible lithium ion intercalation and de-intercalation without huge volume change which consequently prevents the pulverization of active materials during repeated charge and discharge processes. Herein, we prepared hierarchical MoS2–carbon (MoS2–C) microspheres via a continuous and scalable ultrasonic nebulization assisted route. The structure, composition, and electrochemical properties are investigated in detail. The MoS2–C microspheres consist of few-layer MoS2 nanosheets bridged by carbon, which separates the exfoliated MoS2 layers and prevents their aggregation and restacking, thus leading to improved kinetic, enhanced conductivity and structural integrity. The novel architecture offers additional merits such as overall large size and high packing density, which promotes their practical applications. The MoS2–C microspheres have been demonstrated with excellent electrochemical performances in terms of low resistance, high capacity even at large current density, stable cycling performance, etc. The electrodes exhibited 800 mA h g−1 at 1000 mA g−1 over 170 cycles. At a higher current density of 3200 mA g−1, a capacity of 730 mA h g−1 can be also maintained. The MoS2–C microspheres are practically applicable not only because of the continuous and large scale synthesis via the current strategy, but also the possess a robust and integrated architecture which ensures the excellent electrochemical properties.

Size dependent cellular uptake, in vivo fate and light–heat conversion efficiency of gold nanoshells on silica nanorattles

Despite advances in photothermal therapy of gold nanoshells, reliable evaluations of their size dependence on the relative biological effects are needed. We report the size effects of PEGylated gold nanoshells on silica nanorattles (pGSNs) on their cellular uptake, in vivo fate and light-heat conversion efficiency in this study. The results indicate that smaller pGSNs have enhanced cellular uptake by the MCF-7 cells. For in vivo biodistribution study, pGSNs of different particle sizes (84-315 nm) distribute mainly in the liver and spleen in MCF-7 tumor-bearing BALB/c nude mice. Smaller pGSNs have a longer blood-circulation lifetime and higher light-heat conversion efficiency both in vitro and in vivo compared with larger ones. All three sizes of pGSNs can be excreted from the mice body at a slow rate and do not cause tissue toxicity after intravenous injection at a dosage of 20 mg kg(-1) for three times. The data support the feasibility of optimizing the therapeutic process for photothermal cell killing by plasmonic gold nanoshells.