Aifei Wang

pH-Triggered Controlled Drug Release from Mesoporous Silica Nanoparticles via Intracelluar Dissolution of ZnO Nanolids

Acid-decomposable, luminescent ZnO quantum dots (QDs) have been employed to seal the nanopores of mesoporous silica nanoparticles (MSNs) in order to inhibit premature drug (doxorubicin) release. After internalization into HeLa cells, the ZnO QD lids are rapidly dissolved in the acidic intracellular compartments, and as a result, the loaded drug is released into the cytosol from the MSNs. The ZnO QDs behave as a dual-purpose entity that not only acts as a lid but also has a synergistic antitumor effect on cancer cells. We anticipate that these nanoparticles may prove to be a significant step toward the development of a pH-sensitive drug delivery system that minimizes drug toxicity.

Intracellular antioxidants dissolve man-made antioxidant nanoparticles: using redox vulnerability of nanoceria to develop a responsive drug delivery system.

Regeneratable antioxidant property of nanoceria has widely been explored to minimize the deleterious influences of reactive oxygen species. Limited information is, however, available regarding the biological interactions and subsequent fate of nanoceria in body fluids. This study demonstrates a surprising dissolution of stable and ultrasmall (4 nm) cerium oxide nanoparticles (CeO2 NPs) in response to biologically prevalent antioxidant molecules (glutathione, vitamin C). Such a redox sensitive behavior of CeO2 NPs is subsequently exploited to design a redox responsive drug delivery system for transporting anticancer drug (camptothecin). Upon exposing the CeO2 capped and drug loaded nanoconstruct to vitamin c or glutathione, dissolution-accompanied aggregation of CeO2 nanolids unleashes the drug molecules from porous silica to achieve a significant anticancer activity. Besides stimuli responsive drug delivery, immobilization of nanoceria onto the surface of mesoporous silica also facilitates us to gain a basic insight into the biotransformation of CeO2 in physiological mediums.

pH dictates the release of hydrophobic drug cocktail from mesoporous nanoarchitecture.

Combination therapy has been a norm in clinical practice to effectively treat cancer. Besides polytherapy, nowadays, smart and nanobased drug carriers are extensively being explored to deliver drugs according to pathophysiological environment of diseases. In this regard, herein we designed intelligent mesoporous architecture, incorporating both combinational therapy with smart nanotechnology, to simultaneously deliver two highly hydrophobic chemotherapeutic drugs in response to extracellular and/or intracellular acidic environ of tumor. Novelty of the system lies in the employment of acid responsive ZnO QDs to clog not only the nanochannels of mesoporous silica, encapsulating one hydrophobic drug, but also exploitation of chelate forming propensity of another hydrophobic drug (curcumin) to load a significant quantity onto the surface of ZnO nanolids. Cell viability results revealed an extraordinarily high cytotoxic efficiency of that lethal drug cocktail even at a concentration as low as 3 μg/mL nanocarrier. We envision that this sophisticated nanocarrier, which utilizes both interior pore and exterior surface of nanolids for loading different hydrophobic guest molecules and their subsequent acid responsive release, will undoubtedly, illustrates its remarkable potential in targeted chemotherapy.

Robust tri(4-ethynylphenyl)amine-based porous aromatic frameworks for carbon dioxide capture

We report here the synthesis and carbon dioxide capture of a series of porous aromatic framework (PAF) materials assembled using tri(4-ethynylphenyl)amine and various aryl halides via Sonogashira–Hagihara coupling reactions. These PAF materials show moderate surface areas ranging from 370 m2 g−1 to 953 m2 g−1. The functional groups, such as –COOH, –NH2 and –OH, are incorporated into the backbone of the PAF materials. The isosteric heats of CO2 and CO2/N2 selectivities for these PAFs are calculated based on the CO2 and N2 adsorption isotherms measured at 273 and 298 K. It is found that the –NH2 functionalized network shows the highest isosteric heat of CO2 and CO2/N2 selectivity. In addition, the –COOH functionalized network displays the highest CO2 uptake in terms of per unit areas (4.37 μmol m−2, 273 K). The results indicate the incorporation of functional groups is effective for synthesizing CO2-philic PAF networks with enhanced interaction with CO2 molecules.

Lethal drug combination: arsenic loaded multiple drug mesoporous silica for theranostic applications.

Simultaneous delivery of multiple therapeutic agents is of great importance for effective chemotherapy due of its well-known drug synergism and suppression to chemoresistance. We report a new theranostic nanoformulation to shuttle multiple chemotherapeutic agents for successfully exterminating cancer cells. This strategy is based on the fabrication of magnetite doped mesoporous silica nanoparticles (MSNs) in which both internal porous and external surface of MSN are respectively exploited to load two different kinds of cytotoxic cargoes. Notably, an exceptionally high quantity (29%) of poorly hydrophobic drug camptothecin (CPT) is loaded into the nanopores of MSNs; however, in previous reports less than 1% loading efficiency is reported. Following CPT loading in the pores of MSNs, another unconventional but FDA approved arsenic trioxide (ATO) is conjugated onto the surface of nanocomposite via exploiting the thiophilic nature of ATO. Cell inhibition performance of dual drug nanoformulation is significantly higher than single drug formulation, possibly due to additional or synergistic effect, as low as 3 μg/ml of double drug nanocarrier were found effective to exterminate cancer cells. Besides drug delivery, the presence of superparamagnetic magnetite nanocrystals additionally empowers this system to be used as a contrast agent in magnetic resonance (MR) imaging for either monitoring diseased tissues or feedback of chemotherapy. We anticipate that the integration of combination therapy with nanotechnology coupled with versatile magnetic manipulation feature may prove a significant step forward toward the development of effective theranostic agents.

Synthesis of Oxidant Prone Nanosilver To Develop H2O2 Responsive Drug Delivery System

Our immune system uses toxicity of hydrogen peroxide to kill off bacterial invaders. In this contribution, we intended to integrate ROS producing capability of immune system with oxidant-sensitive nature of antibacterial silver nanoparticles (Ag NPs) to develop an oxidant drug delivery system. Prior to execute this strategy, we have developed an efficient one-pot synthetic protocol to produce ultrasmall (5 nm), water-stable, and oxidant-prone Ag NPs. Notably, the yield of as-synthesized Ag NPs is 10-fold higher than standard citrate reduction route. The resulting therapeutically active and well-dispersed Ag NPs are used as nanolids to cap the drug loaded nanochannels of porous silica. Upon exposing to H2O2, dissolution-accompanied aggregation of Ag nanolids unleashes the encapsulated therapeutic entities from channels of nanocarrier. Combination of antibacterial and anti-inflammatory drugs in single nanocarriers can potentially augment the effectiveness of various therapies.

Generation of bimodal porosity via self-extra porogenes in nanoporous carbons for supercapacitor application

In the present study, a facile strategy is proposed for generating bimodal porosity in porous carbons by using a sacrificed metal–organic framework (ZIF-8) as the precursor and additional silica colloids as extra porogenes via further self-assembly. Details in the formation of hierarchical structures are studied by time-dependent XRD and TEM characterizations. As-synthesized hierarchical porous carbons possess micropores (1.0 nm) and mesopores (3–20 nm) that are verified by TEM and N2-sorption measurements. Specific information on carbon structures is supplied by XRD and Raman data. Electrochemical properties have been briefly investigated by cyclic voltammetry and impedance spectroscopy. A highest capacitance of 181 F g−1 and lowest resistance of 0.21 Ω cm2 are obtained between series of ZIF-8 derivative carbons, both of which, along with high electro-stability, show promising applications for these nanoporous carbons in supercapacitors.

Using oxidant susceptibility of thiol stabilized nanoparticles to develop an inflammation triggered drug release system

Inflammation is a complex and dynamic defensive cellular approach to safeguard against deleterious agents; however, an overexpression of such responses frequently results in the development of a number of devastating diseases, such as atherosclerosis, cancer, inflammatory bowel, Alzheimers and Parkinsons diseases. At the site of the inflammation, excessive amount of reactive oxygen species (ROS) are produced, and therefore researchers are now earnestly trying to exploit ROS pathological signals to design oxidative triggered drug release systems. In this study, we report a straightforward strategy to develop an oxidative stress responsive drug release systems. Newly developed, ultra-small, and thiol stabilized zinc sulfide quantum dots (ZnS QDs) are used as nanocaps to regulate the release of anticancer drug (camptothecin) from mesoporous silica nanoparticles (MSNs) in response to oxidative environment. The exposure of capped nanocarrier to a higher concentration of H2O2 fails to open the drug loaded nanochannels; however, an addition of a minute amount of divalent iron, the most abundant transition-metal in the body, readily unseals the nanochannels at considerably lower H2O2 concentrations due to the generation of highly reactive hydroxyl radicals (˙OH). Thiol groups, which stabilize the ZnS nanolids, are actually oxidized by ˙OH and as a result unleash the loaded drug molecules from the channels of silica. In addition to the inflammation-induced drug delivery, this study also provides basic insight into the fate of thiol stabilized nanoparticles upon interaction with hydroxyl radicals.

Acid-induced release of curcumin from calcium containing nanotheranostic excipient.

Poor water solubility is believed one of the most critical problems of numerous promising pharmaceutical ingredients in their successful clinical utilization. Nanomedicine holds considerable promise to address this challenge, because it extends the therapeutic window of hydrophobic drugs through nanonization approach. Recently, the integration of diagnostic agents with smart therapeutic nanocarriers is also an emerging research arena to simultaneously visualize diseased tissues, achieve site specific drug release and track the impact of therapy. In this study, we have developed a biocompatible smart theranostic nanosystem which transports a highly promising hydrophobic drug (curcumin) in response to mildly acidic environment. As calcium is a main constituent of human body, hence we exploited the reversible calcium chelate formation tendency of divalent calcium to load and unload curcumin molecules. Moreover, an emerging T1 contrast agent is also tethered onto the surface of nanocarrier to realize MRI diagnosis application. In-vitro cell experiments revealed a significantly high chemotherapeutic efficiency of curcumin nanoformulation (IC50; 1.67 μg/mL), whereas free curcumin was found ineffective at the corresponding concentration (IC50; 29.72 μg/mL). MR imaging test also validated the performance of resulting system. Our strategy can be extended for the targeted delivery of other hydrophobic pharmaceutical ingredients.

Magnesium hydroxide nanoplates: a pH-responsive platform for hydrophobic anticancer drug delivery

The cost of conventional chemotherapeutic drugs is substantially high, and biomedical researchers are constantly hunting for cheap and effective chemotherapeutic alternatives. Recently, curcumin has emerged as a cost effective anticancer remedy, however, the low bioavailability of curcumin has been a major impediment to its successful utilization for disease management. In this work, we developed a highly biocompatible magnesium hydroxide as an intelligent nanocarrier for delivering curcumin into cancer cells. Curcumin was loaded onto magnesium hydroxide nanoplates via a complexation strategy. Furthermore, these drug conjugated nanoparticles not only achieve efficient loading of a highly hydrophobic drug, but also exhibit pH responsive release in extracellular or intracellular acid environments, validated by in vitro drug release, confocal microscopy and MTT assay. These biocompatible nanoplates can be promising candidates for the further development of smart drug delivery nanodevices.