Zhiqiang Cao

Water-soluble and phosphorus-containing carbon dots with strong green fluorescence for cell labeling

Water-soluble phosphorus-containing carbon dots (PCDs) with strong green fluorescence were synthesized through a facile one-step microwave assisted approach using phosphorus-rich phytic acid as a carbon source. Owing to their strong green fluorescence and low cytotoxicity, the PCDs are promising as bio-imaging agents.

Polycation-b-polyzwitterion copolymer grafted luminescent carbon dots as a multifunctional platform for serum-resistant gene delivery and bioimaging.

Nanomaterials that integrate functions of imaging and gene delivery have been of great interest due to their potential use in simultaneous diagnosis and therapy. Herein, polycation-b-polysulfobetaine block copolymer, poly[2-(dimethylamino) ethyl methacrylate]-b-poly[N-(3-(methacryloylamino) propyl)-N,N-dimethyl-N-(3-sulfopropyl) ammonium hydroxide] (PDMAEMA-b-PMPDSAH) grafted luminescent carbon dots (CDs) were prepared via surface-initiated atom transfer radical polymerization (ATRP) and investigated as a multifunctional gene delivery system (denoted as CD-PDMA-PMPD) in which the CD cores acted as good multicolor cell imaging probes, the cationic PDMAEMA acted as a DNA condensing agent, and the outer shell of zwitterionic PMPDSAH block protected the vector against nonspecific interactions with serum components. As revealed by the fluorescent spectrum study, the photoluminescent attributes, especially the tunable emission property, were well inherited from the parent CDs. The CD-PDMA-PMPD could condense plasmid DNA into nanospheres with sizes of approximate 50 nm at a proper complex ratio, posing little cytotoxicity at higher ratios. It was shown that the hybrid vector exhibited significantly suppressed BSA protein adsorption and superior hemocompatibility compared to those of the widely used PEI25k. In the in vitro transfection assay, an increased serum concentration from 10 to 50% caused a dramatic drop in PEI25k transfection performance, whereas the transfection efficiency of CD-PDMA-PMPD was well maintained; CD-PDMA80-PMPD40 showed 13 and 28 times higher transfection efficiencies than PEI25k at 30 and 50% serum concentration, respectively. Intriguingly, the carbon dots in the transfected cells displayed excitation-dependent fluorescent emissions, portending that this polycation-polyzwitterion modified CD will be a promising theranostic vector with excellent stealth performance.

Strategies on designing multifunctional surfaces to prevent biofilm formation

AbstractBacteria adhesion and biofilm formation have raised severe problems on public health, food industry and many other areas. A variety of reagents and surface coatings have been developed to kill bacteria and/or limit their interaction with surfaces. It has also attracted many efforts to integrate different bactericidal elements together and maximize antibacterial efficiency. Herein, we review mechanisms for both passive and active approaches to resist and kill bacteria respectively, and discuss integrated strategies based on these two approaches. We also offer perspective on future research direction.n

A High Strength Self-Healable Antibacterial and Anti-Inflammatory Supramolecular Polymer Hydrogel

There is a significant cost to mitigate the infection and inflammation associated with the implantable medical devices. The development of effective antibacterial and anti-inflammatory biomaterials with novel mechanism of action has become an urgent task. In this study, a supramolecular polymer hydrogel is synthesized by the copolymerization of N-acryloyl glycinamide and 1-vinyl-1,2,4-triazole in the absence of any chemical crosslinker. The hydrogel network is crosslinked through the hydrogen bond interactions between dual amide motifs in the side chain of N-acryloyl glycinamide. The prepared hydrogels demonstrate excellent mechanical properties-high tensile strength (≈1.2 MPa), large stretchability (≈1300%), and outstanding compressive strength (≈11 MPa) at swelling equilibrium state. A simulation study elaborates the changes of hydrogen bond interactions when 1-vinyl-1,2,4-triazole is introduced into the gel network. It is demonstrated that the introduction of 1-vinyl-1,2,4-triazole endowes the supramolecular hydrogels with self-repairability, thermoplasticity, and reprocessability over a lower temperature range for 3D printing of different shapes and patterns under simplified thermomelting extrusion condition. In addition, these hydrogels exhibit antimicrobial and anti-inflammatory activities, and in vitro cytotoxicity assay and histological staining following in vivo implantation confirm the biocompatibility of the hydrogel. These hydrogels with integrated multifunctions hold promising potential as an injectable biomaterial for treating degenerated soft supporting tissues.

Simple Protein Modification Using Zwitterionic Polymer to Mitigate the Bioactivity Loss of Conjugated Insulin

Polymer-protein conjugation has been extensively explored toward a better protein drug with improved pharmacokinetics. However, a major problem with polymer-protein conjugation is that the polymers drastically reduce the bioactivity of the modified protein. There is no perfect solution to prevent the bioactivity loss, no matter the polymer is conjugated in a non-site specific way, or a more complex site-specific procedure. Here the authors report for the first time that when zwitterionic carboxybetaine polymer (PCB) is conjugated to insulin through simple conventional coupling chemistry. The resulting PCB-insulin does not show a significant reduction of in vitro bioactivity. The obtained PCB-insulin shows two significant advantages as a novel pharmaceutical agent. First, its therapeutic performance is remarkable. For PCB-insulin, there is a 24% increase of in vivo pharmacological activity of lowering blood glucose compared with native insulin. Such uncommonly seen increase has rarely been reported and is expected to be due to both the improved pharmacokinetics and retained bioactivity of PCB-insulin. Second, the production is simple from manufacturing standpoints. Conjugation procedure involves only one-step coupling reaction without complex site-specific linkage technique. The synthesized PCB-insulin conjugates do not require chromatographic separation to purify and obtain particular isoforms.

Superdurable Coating Fabricated from a Double-Sided Tape with Long Term “Zero” Bacterial Adhesion

There is no coating technology currently available to prevent the notorious biofilm formation issue. Here, a potential solution to fully address this tough issue is reported by developing a super-antifouling coating. The use of zwitterionic hydrogel (a double-sided tape) and commercial superglue is combined and a durable and ultrarobust antifouling zwitterionic (DURA-Z) coating is created that can be easily and universally applied on common substrates. Commercial superglue mostly for binding hydrophobic materials is used to strongly immobilize the superhydrophilic DURA-Z coating through interpenetration. DURA-Z coating effectively solves several key challenges preventing the current antifouling coatings from practical use, including difficult fabrication, low efficacy, poor toughness, and durability. The fabricated DURA-Z coating retains antifouling property after 90 d of immersion in water, 50 d of buffer shearing, and 30 d of water flushing, and after repeated knife scratch and sandpaper abrasion under 570 kPa. The DURA-Z coating achieves a rarely reported long-term biofilm resistance to both Gram-positive and Gram-negative bacteria and fungi: it remains almost zero microbe adhesion after continuously challenged by more than 109 cells mL-1 culture medium for 30 d.

Micelles with ultralow critical micelle concentration as carriers for drug delivery

Conventional micellar carriers disassemble into free surfactants when diluted at concentrations below the critical micelle concentration (CMC). This limits the bioavailability in vivo of injected hydrophobic drugs encapsulated in micellar systems. Here, we show that a micelle comprising a superhydrophilic zwitterionic polymer domain and a superhydrophobic lipid domain has an undetectable CMC below 10−6u2009mM—a value that is orders of magnitude lower than the CMCs (>10−3u2009mM) of typical micellar systems. We also show that zwitterionic moieties or zwitterionic polymers added to a micelle solution stabilize the micelles at concentrations below their inherent CMC. In a mouse model of melanoma, ultralow-CMC micelles encapsulating docetaxel led to the complete eradication of tumours, whereas conventional docetaxel micellar formulations did not reverse tumour growth. Ultralow-CMC micelles might become next-generation carriers for drug delivery.Polymer–lipid micelles with an ultralow undetectable critical micelle concentration make ultrastable drug carriers that significantly enhance therapeutic outcomes in a mouse model of melanoma.

Strategies to improve micelle stability for drug delivery

Micelles have been studied as drug delivery carriers for decades. Their use can potentially result in high drug accumulation at the target site through the enhanced permeability and retention effect. Nevertheless, the lack of stability of micelles in the physiological environment limits their efficacy as a drug carrier. In particular, micelles tend to disassociate and prematurely release the encapsulated drugs, lowering delivery efficacy and creating toxicity concerns. Many efforts to enhance the stability of micelles have focused mainly on decreasing the critical micelle forming concentration and improving blood circulation. Herein, we review different strategies including crosslinking and non-crosslinking approaches designed to stabilize micelles and offer perspectives on future research directions.

L-Carnitine derived zwitterionic betaine materials

An L-carnitine derived zwitterionic betaine material was developed. The synthesized L-carnitineMA was the first zwitterionic betaine monomer from natural feedstocks. In the models of Surface coating and hydrogel, the L-carnitineMA material was able to achieve superior anti-fouling performance as good as state-of-the-art zwitterionic betaine materials.