Si Yu Tan

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.

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.

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.

Synergistic Effect of Mesoporous Co3O4 Nanowires Confined by N‐Doped Graphene Aerogel for Enhanced Lithium Storage

A one-step multipurpose strategy is developed to realize a sophisticated design that simultaneously integrates three desirable components of nitrogen dopant, 3D graphene, and 1D mesoporous metal oxide nanowires into one hybrid material. This facile synthetic strategy includes a one-step hydrothermal reaction followed by topotactic calcination. The utilization of urea as the starting reagent enables the precipitation of precursor nanowires and concurrent doping of nitrogen heteroatoms on graphene during hydrothermal reaction, while at the same time the graphene nanosheets are self-assembled to afford a 3D scaffold. Detailed characterizations on the final calcined product are conducted to confirm the phase purity, porosity, nitrogen composition, and morphology. The integration of two building blocks, i.e., flexible graphene nanosheets and Co3 O4 nanowires, enables various intertwining behaviors such as seaming, bridging, hooping, bundling, and sandwiching, of which synergistic effect substantially enhances electrical and electrochemical properties of the resultant hybrid. For lithium ion battery application of the hybrid, a remarkably high capacity more than 1200 mA h g(-1) (at 100 mA g(-1) ) is stabilized over 100 cycles with coulombic efficiency higher than 97%. Even during rapid discharge/charge processes (1000 mA g(-1) ), a reversible charge capacity of 812 mA h g(-1) is still retained after 230 cycles.

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.

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.

Redox and pH Dual Responsive Polymer Based Nanoparticles for In Vivo Drug Delivery

Responsive nanomaterials have emerged as promising candidates as drug delivery vehicles in order to address biomedical diseases such as cancer. In this work, polymer-based responsive nanoparticles prepared by a supramolecular approach are loaded with doxorubicin (DOX) for the cancer therapy. The nanoparticles contain disulfide bonds within the polymer network, allowing the release of the DOX payload in a reducing environment within the endoplasm of cancer cells. In addition, the loaded drug can also be released under acidic environment. In vitro anticancer studies using redox and pH dual responsive nanoparticles show excellent performance in inducing cell death and apoptosis. Zebrafish larvae treated with DOX-loaded nanoparticles exhibit an improved viability as compared with the cases treated with free DOX by the end of a 3 d treatment. Confocal imaging is utilized to provide the daily assessment of tumor size on zebrafish larva models treated with DOX-loaded nanoparticles, presenting sustainable reduction of tumor. This work demonstrates the development of functional nanoparticles with dual responsive properties for both in vitro and in vivo drug delivery in the cancer therapy.

A dual responsive “turn-on” fluorophore for orthogonal selective sensing of biological thiols and hydrogen peroxide

Both thiols and hydrogen peroxide (H2O2) have great correlations with cancer and other diseases, and hence detection probes for sensing these agents may serve as early diagnostic tools. In this article, we report the development of a dual responsive probe that has the ability to generate two different responses upon reacting with thiols and H2O2 in a highly selective manner. The probe (FLB2SSCou) consists of a coumarin unit and a diboron xanthene spiro isobenzofuran group bridged by a disulfide bond. The detection experiments show that the probe could selectively respond to thiols and H2O2 when screening a substrate library containing 20 amino acids, homocysteine, glutathione, dithiothreitol and H2O2. The initial off state of the probe was a result of photo-induced electron transfer (PET) from the coumarin group to the non-fluorescing diboron xanthene spiro isobenzofuran group bridged by a disulfide bond. Reductive cleavage of the disulfide bond leads to the termination of this PET process, thus switching on the fluorescence of the probe. On the other hand, the oxidation of the diboron group by H2O2 converts the non-fluorescing group into a highly fluorescing fluorescein group. Time-dependent density functional theory calculations were then performed to explain the PET process, and the obtained results indicate that the PET process occurs from the second excited state (S2) into the first excited state (S1). Finally, imaging and detection experiments of the probe on HeLa cancer cells were conducted by means of the fluorescence microscopy and flow cytometry technique. It was observed that the fluorescence of the FLB2SSCou probe could be switched on by endogenous thiols and exogenous H2O2, demonstrating the applicability of this probe in both extracellular and intracellular environments. The present work exhibits the novel development of a dual responsive probe in contrast to commonly reported single responsive fluorescent probes, which may inspire the future design of multiple responsive fluorescent probes.