Liqun Xu

Functionalized Mesoporous Silica Nanoparticles with Mucoadhesive and Sustained Drug Release Properties for Potential Bladder Cancer Therapy

The synthesis of a series of β-cyclodextrin modified mesoporous silica nanoparticles with hydroxyl, amino, and thiol groups was described. A comparison of their mucoadhesive properties and potential as a drug delivery system for superficial bladder cancer therapy was made. The thiol-functionalized nanoparticles exhibit significantly higher mucoadhesivity on the urothelium as compared to the hydroxyl- and amino-functionalized nanoparticles. This is attributed to the formation of disulfide bonds between the thiol-functionalized nanoparticles and cysteine-rich subdomains of mucus glycoproteins. An anticancer drug, doxorubicin, was loaded into the mesopores of the thiol-functionalized nanoparticles, and sustained drug release triggered by acidic pH was achieved. The present study demonstrates that thiol-functionalized mesoporous silica nanoparticles are promising as a mucoadhesive and sustained drug delivery system for superficial bladder cancer therapy.

Polymeric nanoparticles with encapsulated superparamagnetic iron oxide and conjugated cisplatin for potential bladder cancer therapy.

Amphiphilic poly(ε-caprolactone)-b-poly(propargyl methacrylate-click-mercaptosuccinic acid-co-poly(ethylene glycol) methyl ether methacrylate) (PCL-b-P(PMA-click-MSA-co-PEGMA)) were synthesized by a combination of ring-opening polymerization, reversible addition-fragmentation chain transfer (RAFT) polymerization, and thiol-yne click reaction. The hydrophobic PCL core can be used to load superparamagnetic iron oxide nanoparticles (SPIONs), while the pendant dicarboxylic groups in the hydrophilic shell are used to coordinate cisplatin. These SPIONs-loaded, cisplatin-conjugated polymeric nanoparticles (Pt-Fe-PNs) are superparamagnetic at room temperature and are mucoadhesive. Release of cisplatin from Pt-Fe-PNs in artificial urine at 37 °C was characterized by an initial burst release with a release of ∼30% of the cisplatin in the first 4 h followed by a slow sustained release over 4 days. The cisplatin release can be further enhanced by increasing the temperature. These Pt-Fe-PNs can effectively induce cytotoxicity against UMUC3 bladder cancer cells with IC(50) of 32.3 μM. These results indicate that Pt-Fe-PNs is potentially a promising cisplatin delivery vehicle which can be combined with SPIONs-induced hyperthermia for bladder cancer therapy.

Smart nanofibers with a photoresponsive surface for controlled release.

A novel photocontrolled ON-OFF release system for the alpha-cyclodextrin-5-fluorouracial (alpha-CD-5FU) prodrug, based on host-guest interaction on the photoresponsive and cross-linked nanofiber surface, was demonstrated. The nanofibers with a stimuli-responsive surface were electrospun from the block copolymer prepared via controlled radical polymerization, followed by surface modification via Click Chemistry, and loading of the prodrug via host-guest interaction.

Interpenetrating Network Hydrogels via Simultaneous Click Chemistry and Atom Transfer Radical Polymerization

Simultaneous interpenetrating polymer networks (sIPNs) from concurrent copper(I)-catalyzed azide-alkyne cycloaddition click chemistry and atom transfer radical polymerization (ATRP) are described. Semi-sIPN of poly(ethylene glycol)/poly(2-hydroxyethyl methacrylate) (semi-PEG/PHEMA-sIPN) was first prepared via simultaneous click chemistry and ATRP from a mixture of poly(ethylene glycol)-diazide (N3-PEG-N3, Mn=4000 g/mol), tetrakis(2-propynyloxymethyl)methane (TPOM), ethyl-2-bromobutyrate (EBB), CuBr, pentamethyldiethylenetriamine (PMDETA), and 2-hydroxyethyl methacrylate (HEMA) in dimethylformamide (DMF). Full sIPN of PEG/PHEMA (full-PEG/PHEMA-sIPN) was then prepared via simultaneous click chemistry and ATRP from a mixture of N3-PEG-N3 (Mn=4000 g/mol), TPOM, EBB, CuBr, PMDETA, HEMA, and poly(ethylene glycol) diacrylate) (PEGDA, Mn=575) in DMF. Both the semi- and full-sIPNs exhibit a fast gelation rate and high gel yield. The sIPNs also exhibit high swelling ratios and good mechanical and antifouling properties. The morphology and thermal behavior of the sIPNs were studied by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). These sIPNs could find applications as biomaterials for contact lenses, biomedical materials, artificial organs, and drug delivery systems.

In Situ Synthesis and Nonvolatile Rewritable‐Memory Effect of Polyaniline‐Functionalized Graphene Oxide

A new polyaniline (PANI)-functionalized graphene oxide (GO-PANI) was prepared by using an in situ oxidative graft polymerization of aniline on the surface of GO. Its highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), ionization potential (IP), and electron affinity (EA) values experimentally estimated by the onset of the redox potentials were -5.33, -3.57, 5.59, and 3.83u2005eV, respectively. A bistable electrical-switching effect was observed in electronic device with the GO-PANI film sandwiched between the indium tin oxide (ITO) and Al electrodes. This device exhibited two accessible conductivity states, that is, the low-conductivity (OFF) state and the high-conductivity (ON) state, and can be switched to the ON state under a negative electrical sweep, and can also be reset to the initial OFF state by a reverse (positive) electrical sweep. The ON state is nonvolatile and can withstand a constant voltage stress of -1u2005V for 3u2005h and 10(8) read cycles at -1u2005V under ambient conditions. The nonvolatile nature of the ON state and the ability to write, read, and erase the electrical states, fulfill the functionality of a rewritable memory. An ON/OFF current ratio of more than 10(4) at -1u2005V achieved in this memory device is high enough to promise a low misreading rate through the precise control of the ON and OFF states. The mechanism associated with the memory effects was elucidated from molecular simulation results.

Water-soluble highly fluorescent poly[poly(ethylene glycol) methyl ether methacrylate] for cell labeling

A novel fluorescent brush-like poly[poly(ethylene glycol) methyl ether methacrylate] (P(PEGMA)) has been synthesized via facile atom transfer radical polymerization using perylene-3,4,9,10-tetracarboxylic acid bisimide (PBI) as the initiator. The PBI–P(PEGMA) polymer has strong fluorescence in water and will be an effective bio-dye for cell labeling.

A well-defined amphiphilic polymer co-network from precise control of the end-functional groups of linear RAFT polymers

Linear polystyrene (PS) with well-defined molecular structure and accurate numbers of bromo groups on both ends were synthesized via multiple-step alternative RAFT polymerization of N-bromopropyl maleimide and β-pinene monomers. The bromo end groups were transformed into the azido moieties via nucleophilic substitution. The reaction of as-synthesized linear PS having a named number of azide groups on ends ((N3)x–PS–(N3)x) with mono- and dialkynyl-terminated PEG (dA-PEG) via copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) leads to the formation of the well-defined PS–PEG amphiphilic copolymers and polymeric co-networks (APCNs). The as-prepared APCNs exhibit unique ordered separated hydrophilic and hydrophobic phases, and a variable swelling capacity both in polar and non-polar solvents.

Tannic acid anchored layer-by-layer covalent deposition of parasin I peptide for antifouling and antimicrobial coatings

Tannic acid can serve as an initiator anchor for surface functionalization. Parasin I is an antimicrobial peptide derived from histone. Multilayer coatings on stainless steel were prepared by alternative deposition of these two materials via the Michael addition/Schiff base reaction-enabled layer-by-layer (LBL) deposition technique. The as-prepared multilayer coating exhibits good resistance to Gram-negative bacteria (Pseudomonas sp. and E. coli), Gram-positive bacteria (S. aureus and S. epidermidis) and microalgae (Amphora coffeaeformis). The antifouling and antimicrobial efficacy increase with an increasing number of the assembled multilayers. The stability and durability of multilayer coatings were also ascertained by prolonged exposure to seawater. The LBL covalently deposited multilayer coatings are thus potentially useful as effective and environmental benign coatings to combat biofouling in marine and aqueous environments.

Preparation of Fluorescent Organometallic Porphyrin Complex Nanogels of Controlled Molecular Structure via Reverse-Emulsion Click Chemistry

Here, we are the first to report a novel approach to preparing well-defined poly(ethylene glycol) (PEG) fluorescent nanogels, with well-defined molecular structures and desired functionalities via reverse (mini)emulsion copper(I)-catalyzed azide-alkyne cycloaddition (REM-CuAAC). Nanogels with hydroxyl groups and Ga-porphyrin complex (Ga-porphyrin-OH nanogels), as well as with Ga-porphyrin complex and folate functional groups (Ga-porphyrin-FA), are successfully prepared. Nanogels of 30 and 120 nm in diameter are obtained and they exhibit an emission maxima within the wavelength range 700-800 nm. The nanogels could find uses in near infrared (NIR) imaging attributable to their fluorescence and their functionality for cell affinity.

Co-delivery of peptide-modified cisplatin and doxorubicin via mucoadhesive nanocapsules for potential synergistic intravesical chemotherapy of non-muscle-invasive bladder cancer.

Synergistic effect against UMUC3 bladder cancer cells was demonstrated via a two-in-one combination of doxorubicin (Dox) and peptide-modified cisplatin (Pt-ALy) loaded in positively charged mucoadhesive chitosan-polymethacrylic acid (CM) nanocapsules. The in vitro killing efficacy of the dual drug-loaded nanocapsules (CM-Dox-PtALy) against UMUC3 cells after 4h- and 72h-treatment is much higher (with 5-16 times lower IC50) than either Dox- or Pt-ALy-loaded nanocapsules, resulting in combination indexes of much less than 1 (i.e. obvious synergism) at fractions of affected cells ranging from 0.2 to 0.8. The dose reduction index of Pt-ALy for 72h-treatment is higher than for 4h-treatment, suggesting that Dox in CM-Dox-PtALy played a more significant role in the synergy in the former. The drug-loaded CM nanocapsules are readily taken in by the cells as shown by flow cytometry, confocal laser scanning microscopy and inductively coupled plasma mass spectrometry. Microscopy observations indicate that CM nanocapsules attach strongly on the luminal surface of the bladder with no obvious damage of the urothelium, supporting our objective of prolonging the dwell time of the drug-loaded nanocapsules for intravesical applications. Our study indicates that the mucoadhesive CM-Dox-PtALy nanocapsules have a high drug loading and a sustained release profile, and thus, are promising for synergistic intravesical chemotherapy of non-muscle-invasive bladder cancers.