Fangqiong Tang

Mesoporous Silica Nanoparticles: Synthesis, Biocompatibility and Drug Delivery

In the past decade, mesoporous silica nanoparticles (MSNs) have attracted more and more attention for their potential biomedical applications. With their tailored mesoporous structure and high surface area, MSNs as drug delivery systems (DDSs) show significant advantages over traditional drug nanocarriers. In this review, we overview the recent progress in the synthesis of MSNs for drug delivery applications. First, we provide an overview of synthesis strategies for fabricating ordered MSNs and hollow/rattle-type MSNs. Then, the in vitro and in vivo biocompatibility and biotranslocation of MSNs are discussed in relation to their chemophysical properties including particle size, surface properties, shape, and structure. The review also highlights the significant achievements in drug delivery using mesoporous silica nanoparticles and their multifunctional counterparts as drug carriers. In particular, the biological barriers for nano-based targeted cancer therapy and MSN-based targeting strategies are discussed. We conclude with our personal perspectives on the directions in which future work in this field might be focused.

The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function

The interaction between nanoparticles (NPs) and cells has been studied extensively, but the effect of particle shape on cell behavior has received little attention. Herein three different shaped monodisperse mesoporous silica nanoparticles (MSNs) of similar particle diameter, chemical composition and surface charge but with different aspect ratios (ARs, 1, 2, 4) were specially designed. Then the effects of particle shape of these three different shaped particles on cellular uptake and behavior were studied. The results indicated that these different shaped particles were readily internalized in A375 human melanoma (A375) cells by nonspecific cellular uptake. Particles with larger ARs were taken up in larger amounts and had faster internalization rates. Likewise, it was also found that particles with larger ARs had a greater impact on different aspects of cellular function including cell proliferation, apoptosis, cytoskeleton formation, adhesion and migration. These results show that nanoparticles should no longer be viewed as simple carriers for biomedical applications, but can also play an active role in mediating biological effects. Therefore, our findings may provide useful information for the development of new strategies for the design of efficient drug delivery nanocarriers and therapeutic systems and provide insights into nanotoxicity.

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

In vivo delivery of silica nanorattle encapsulated docetaxel for liver cancer therapy with low toxicity and high efficacy.

Mesoporous silica nanomaterial is one of the most promising candidates as drug carrier for cancer therapy. Herein, in vitro and in vivo study of silica nanorattle (SN) with mesoporous and rattle-type structure as a drug delivery system was first reported. Hydrophobic antitumor drug docetaxel (Dtxl) was loaded into the PEGylated silica nanorattle (SN-PEG) with a diameter of 125 nm via electrostatic absorption. In human liver cancer cell Hep-G2, the half-maximum inhibiting concentration (IC(50)) of silica nanorattle encapsulated docetaxel (SN-PEG-Dtxl) was only 7% of that of free Dtxl at 72 h. In vivo toxicity assessment showed that both nanocarrier of silica nanorattle (40 mg/kg, single dose) and SN-PEG-Dtxl (20 mg/kg of Dtxl, three doses) had low systematic toxicity in healthy ICR mice. The SN-PEG-Dtxl (20 mg/kg, intravenously) showed greater antitumor activity with about 15% enhanced tumor inhibition rate compared with Taxotere on the marine hepatocarcinoma 22 subcutaneous model. The results prove that the SN-PEG-Dtxl has low toxicity and high therapy efficacy, which provides convincing evidence for the silica nanorattle as a promising candidate for a drug delivery system.

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 ]

Silica nanorattle-doxorubicin-anchored mesenchymal stem cells for tumor-tropic therapy.

Low targeting efficiency is one of the biggest limitations for nanoparticulate drug delivery system-based cancer therapy. In this study, an efficient approach for tumor-targeted drug delivery was developed with mesenchymal stem cells as the targeting vehicle and a silica nanorattle as the drug carrier. A silica nanorattle-doxorubicin drug delivery system was efficiently anchored to mesenchymal stem cells (MSCs) by specific antibody-antigen recognitions at the cytomembrane interface without any cell preconditioning. Up to 1500 nanoparticles were uploaded to each MSC cell with high cell viability and tumor-tropic ability. The intracellular retention time of the silica nanorattle was no less than 48 h, which is sufficient for cell-directed tumor-tropic delivery. In vivo experiments proved that the burdened MSCs can track down the U251 glioma tumor cells more efficiently and deliver doxorubicin with wider distribution and longer retention lifetime in tumor tissues compared with free DOX and silica nanorattle-encapsulated DOX. The increased and prolonged DOX intratumoral distribution further contributed to significantly enhanced tumor-cell apoptosis. This strategy has potential to be developed as a robust and generalizable method for targeted tumor therapy with high efficiency and low systematic toxicity.

A practical glucose biosensor based on Fe3O4 nanoparticles and chitosan/nafion composite film

A practical glucose biosensor was developed by combining the intrinsic peroxidase-like activity of Fe(3)O(4) nanoparticles (Fe(3)O(4) NPs) and the anti-interference ability of the nafion film. Glucose oxidase (GOD) was simply mixed with Fe(3)O(4) NPs and cross-linked on the Pt electrode with chitosan (Cs) medium by glutaraldehyde, and then covered with a thin nafion film. The biosensor showed high sensitivity (11.54 microAcm(-2)mM(-1)), low detection limit (6 x10(-6)M), and good storage stability. A linear calibration plot was obtained in the wide concentration range from 6 x10(-6) to 2.2 x10(-3)M. The modified electrode could virtually eliminate the interference during the detection of glucose. Furthermore, the biosensor was successfully applied to detect glucose in human serum sample. This fabrication of glucose biosensor was of considerable interest due to its promise for simple procedure and optimizing conditions in practical application.

The absorption, distribution, excretion and toxicity of mesoporous silica nanoparticles in mice following different exposure routes

Mesoporous silica nanoparticles (MSNs) are emerging as one of the promising nanomaterials for biomedical applications, but the nanomaterials-body interaction exposed by different administration routes remained poorly understood. In the present study, a systematic investigation of the absorption, distribution, excretion and toxicity of silica nanoparticles (SNs) with the average size of 110 nm after four different exposure routes including intravenous, hypodermic, intramuscular injection and oral administration to mice were achieved. The results showed that a fraction of the SNs administrated by the intramuscular and hypodermic injection could cross different biological barriers into the liver but with a low absorption rate. Exposing by oral administration, SNs were absorbed into the intestinal tract and persisted in the liver. And SNs administrated by intravenous injection were mainly present in the liver and spleen. In addition, SNs could cause inflammatory response around the injection sites after intramuscular and hypodermic injection. It was also found that SNs were mainly excreted through urine and feces after different exposure routes. This study will be helpful for selecting the appropriate exposed routes for the development of nanomaterials-based drug delivery system for biomedical applications.

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]

A simple and sensitive fluorescence biosensor for detection of organophosphorus pesticides using H2O2-sensitive quantum dots/bi-enzyme

In this paper, we have developed a simple, fast, convenient and sensitive method for determination of organophosphorus pesticides in real samples based on inhibition mechanism of acetylcholinesterase (AChE). The biosensor is composed of enzymes (AChE and ChOx (choline oxidase)), QDs and acetylcholine (ACh), without any complex process of assembly for biosensor. After the experimental conditions are optimized, the limit of detection (LOD) for dichlorvos (DDVP) is found to be 4.49nM. Two linear ranges allow a wide determination of DDVP concentration from 4.49nM to 6780nM. Furthermore, a possible mechanism is put forward to explain the fluorescence quenching of CdTe QDs in the presence of H2O2. More importantly, the obtained biosensor is proven to be suitable for the detection of residues of organophosphorus pesticides (OPs) in real examples. The excellent performance of this biosensor will facilitate future development of rapid and high-throughput detection of organophosphorus pesticides.