Chung Yen Ang

Polymer-Coated Hollow Mesoporous Silica Nanoparticles for Triple-Responsive Drug Delivery.

In this study, pH, reduction and light triple-responsive nanocarriers based on hollow mesoporous silica nanoparticles (HMSNs) modified with poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) were developed via surface-initiated atom transfer radical polymerization. Both reduction-cleavable disulfide bond and light-cleavable o-nitrobenzyl ester were used as the linkages between HMSNs and pH-sensitive PDEAEMA polymer caps. A series of characterization techniques were applied to characterize and confirm the structures of the intermediates and final nanocarriers. Doxorubicin (DOX) was easily encapsulated into the nanocarriers with a high loading capacity, and quickly released in response to the stimuli of reducing agent, acid environment or UV light irradiation. In addition, flow cytometry analysis, confocal laser scanning microscopy observations and cytotoxicity studies indicated that the nanocarriers were efficiently internalized by HeLa cancer cells, exhibiting (i) enhanced release of DOX into the cytoplasm under external UV light irradiation, (ii) better cytotoxicity against HeLa cells, and (iii) superior control over drug delivery and release. Thus, the triple-responsive nanocarriers present highly promising potentials as a drug delivery platform for cancer therapy.

Functional Silica Nanoparticles for Redox-Triggered Drug/ssDNA Co-delivery

A mesoporous silica nanoparticle (MSNP) based co-delivery system is developed in order to deliver simultaneously drug and single strand DNA (ssDNA) in a controlled manner. Negatively charged ssDNA as a model gene is immobilized onto the surface of positively charged ammonium-functionalized MSNPs through electrostatic interaction, effectively blocking the loaded drugs within the mesopores of MSNPs. When the pre-installed disulfide bond on the ammonium unit is broken by the addition of the reducing agent such as dithiothreitol or glutathione, the ssDNA network on the surface is freed, leading to the release of the loaded drug molecules from the mesopores. The cell investigations indicate that the functional nanoparticles have a very low cytotoxicity under the concentrations measured. The doxorubicin-loaded and ssDNA-coated nanoparticles show an enhanced cellular internalization, leading to a successful drug/ssDNA co-delivery in vitro for significant apoptosis of Hela cancer cells as compared with that of free doxorubicin. The obtained experimental results indicate promising applications of the functional nanoparticles in cancer treatment.

Clicked Isoreticular Metal–Organic Frameworks and Their High Performance in the Selective Capture and Separation of Large Organic Molecules

Three highly porous metal-organic frameworks (MOFs) with a uniform rht-type topological network but hierarchical pores were successfully constructed by the assembly of triazole-containing dendritic hexacarboxylate ligands with Zn(II) ions. These transparent MOF crystals present gradually increasing pore sizes upon extension of the length of the organic backbone, as clearly identified by structural analysis and gas-adsorption experiments. The inherent accessibility of the pores to large molecules endows these materials with unique properties for the uptake of large guest molecules. The visible selective adsorption of dye molecules makes these MOFs highly promising porous materials for pore-size-dependent large-molecule capture and separation.

Luminescent Color Conversion on Cyanostilbene‐Functionalized Quantum Dots via In‐situ Photo‐Tuning

Photo-responsive CdSe quantum dots functionalized with the cyanostilbene unit are synthesized. The as-prepared quantum dot hybrid reveals a photo-tunable dual fluorescent characteristic. White light emission can be generated in situ from the hybrid through photoirradiation to adjust the relative intensities of the two complementary emissions. Luminescent color conversion through yellow, white, and blue can be realized by varying the photoirradiation time.

Photoswitchable supramolecular catalysis by interparticle host-guest competitive binding.

On and off: ester hydrolysis catalyzed by a Zn(II) -coordinated β-cyclodextrin dimer can be switched on and off using light in the presence of gold nanoparticles with azobenzene units attached to their surfaces. Under visible light, the azobenzene units are trans and bind tightly to the dimer, thus leading to reduced catalysis. Under UV light, the azobenzene units are cis and bind loosely to the dimer, thus allowing substrates to bind and hydrolysis to occur.

Supramolecular nanoparticle carriers self-assembled from cyclodextrin- and adamantane-functionalized polyacrylates for tumor-targeted drug delivery

The advancement of nanobiotechnology has led to the development of various techniques for addressing target-specific drug delivery issues. In this article, we successfully developed a supramolecular self-assembly approach for the fabrication of polyacrylate-based nanoparticles with simultaneous loading of the anticancer drug doxorubicin (DOX) for targeted delivery towards cancer treatment in vitro and in vivo. Two types of polyacrylates functionalized with adamantane and β-cyclodextrin respectively could self-assemble to form supramolecular nanoparticles through strong host-guest complexation between adamantane and β-cyclodextrin. Folic acid was incorporated within the supramolecular nanoparticles in order to impart the targeting specificity towards selected cancerous cell lines, namely MDA-MB231 and B16-F10. The as-synthesized supramolecular nanoparticles were fully characterized by several techniques, revealing an average nanoparticle size of 35 nm in diameter, which is small enough for excellent blood circulation. The cytotoxicity studies indicate that the supramolecular nanoparticles without drug loading were non-cytotoxic under the concentrations measured, while DOX-loaded supramolecular nanoparticles showed significant cytotoxicity. In order to investigate the targeting specificity of DOX-loaded supramolecular nanoparticles towards the cancerous cells, a healthy cell line model HEK293 was employed for carrying out the comparison studies. Due to the presence of the targeting ligand, experimental results demonstrate that the supramolecular nanoparticles were highly specific for targeting the cancerous cells, but not for HEK293 cells. After the in vitro investigations, the in vivo drug delivery study using DOX-loaded supramolecular nanoparticles was performed. Tumor-bearing nude mice were treated with DOX-loaded supramolecular nanoparticles, and the analysis results indicate that DOX-loaded supramolecular nanoparticles have the capability to enhance the therapeutic effects of DOX for effectively inhibiting the tumor growth. Thus, the self-assembled polymeric nanoparticles exhibit a highly promising potential to serve as drug carriers for targeted drug delivery towards improved cancer treatment.

Polymeric Prodrug Grafted Hollow Mesoporous Silica Nanoparticles Encapsulating Near-Infrared Absorbing Dye for Potent Combined Photothermal-Chemotherapy.

In this study, polymeric prodrug coated hollow mesoporous silica nanoparticles (HMSNs) with encapsulated near-infrared (NIR) absorbing dye were prepared and explored for combined photothermal-chemotherapy. A copolymer integrated with tert-butoxycarbonyl protected hydrazide groups and oligoethylene glycols was initially grafted on the surface of HMSNs via reversible addition-fragmentation chain-transfer (RAFT) polymerization followed by the deprotection to reactivate the hydrazide groups for the conjugation of anticancer drug doxorubicin (DOX). DOX was covalently bound onto the polymer substrate by acid-labile hydrazone bond and released quickly in weak acidic environment for chemotherapy. The hollow cavity of HMSNs was loaded with an NIR absorbing dye IR825 to form the final multifunctional hybrid denoted as HMSNs-DOX/IR825. The hybrid exhibited good dispersity and stability as well as high light-to-heat conversion efficiency. As revealed by confocal microscopy and flow cytometry analysis, the hybrid was efficiently taken up by cancer cells, and the conjugated DOX could be released under the cellular environment. In vitro cytotoxicity study demonstrated that anticancer activity of HMSNs-DOX/IR825 could be significantly improved by the NIR irradiation, which led to a satisfactory therapeutic efficacy through the combination treatment. Thus, the developed hybrid could be a promising candidate for the combined photothermal-chemotherapy of cancer.

In Situ Integration of Anisotropic SnO2 Heterostructures inside Three-Dimensional Graphene Aerogel for Enhanced Lithium Storage

Three-dimensional (3D) graphene aerogel (GA) has emerged as an outstanding support for metal oxides to enhance the overall energy-storage performance of the resulting hybrid materials. In the current stage of the studies, metals/metal oxides inside GA are in uncrafted geometries. Introducing structure-controlled metal oxides into GA may further push electrochemical properties of metal oxide-GA hybrids. Using rutile SnO2 as an example, we demonstrated here a facile hydrothermal strategy combined with a preconditioning technique named vacuum-assisted impregnation for in situ construction of controlled anisotropic SnO2 heterostructures inside GA. The obtained hybrid material was fully characterized in detail, and its formation mechanism was investigated by monitoring the phase-transformation process. Rational integration of the two advanced structures, anisotropic SnO2 and 3D GA, synergistically led to enhanced lithium-storage properties (1176 mAh/g for the first cycle and 872 mAh/g for the 50th cycle at 100 mA/g) as compared with its two counterparts, namely, rough nanoparticles@3D GA and anisotropic SnO2@2D graphene sheets (618 and 751 mAh/g for the 50th cycle at 100 mA/g, respectively). It was also well-demonstrated that this hybrid material was capable of delivering high specific capacity at rapid charge/discharge cycles (1044 mAh/g at 100 mA/g, 847 mAh/g at 200 mA/g, 698 mAh/g at 500 mA/g, and 584 mAh/g at 1000 mA/g). The in situ integration strategy along with vacuum-assisted impregnation technique presented here shows great potential as a versatile tool for accessing a variety of sophisticated smart structures in the form of anisotropic metals/metal oxides within 3D GA toward useful applications.

Drug encapsulation and release by mesoporous silica nanoparticles : the effect of surface functional groups

Mesoporous silica nanoparticles (MSNPs) have been widely used as drug carriers for stimuli-responsive drug delivery. Herein, a catalysis screening technique was adopted for analyzing the effects of chain length, terminal group, and density of disulfide-appended functional ligands on the surface of MSNPs on drug-loading capacity and glutathione-triggered drug-release kinetics. The ligand with an intermediate length (5 carbon atoms) and a bulky terminal group (cyclohexyl) that complexes with theβ-cyclodextrin ring showed the highest drug loading capacity as well as good release kinetics. In addition, decreasing the surface coverage of the functional ligands led to an enhancement in drug release. In vitro drug-delivery experiments on a melanoma cell line (B16-F10) by using the functionalized MSNPs further supported the conclusion. The results obtained may serve as a general guide for developing more effective MSNP systems for drug delivery.

“Turn-on” fluorescence probe integrated polymer nanoparticles for sensing biological thiol molecules

A “turn-on” thiol-responsive fluorescence probe was synthesized and integrated into polymeric nanoparticles for sensing intracellular thiols. There is a photo-induced electron transfer process in the off state of the probe, and this process is terminated upon the reaction with thiol compounds. Configuration interaction singles (CIS) calculation was performed to confirm the mechanism of this process. A series of sensing studies were carried out, showing that the probe-integrated nanoparticles were highly selective towards biological thiol compounds over non-thiolated amino acids. Kinetic studies were also performed to investigate the relative reaction rate between the probe and the thiolated amino acids. Subsequently, the Gibbs free energy of the reactions was explored by means of the electrochemical method. Finally, the detection system was employed for sensing intracellular thiols in cancer cells, and the sensing selectivity could be further enhanced with the use of a cancer cell-targeting ligand in the nanoparticles. This development paves a path for the sensing and detection of biological thiols, serving as a potential diagnostic tool in the future.