Mn-doped Ti-based MOFs for magnetic resonance imaging-guided synergistic microwave thermal and microwave dynamic therapy of liver cancer.

Currently, precise ablation of tumors without damaging the surrounding normal tissue is still an urgent problem for clinical microwave therapy of liver cancer. Herein, we synthesized Mn-doped Ti MOFs (Mn-Ti MOFs) nanosheets by in-situ doping method and applied them for microwave therapy. Infrared thermal imaging results indicate Mn-Ti MOFs can rapidly increase the temperature of normal saline, attributing to the porous structure improving microwave-induced ion collision frequency. Moreover, Mn-Ti MOFs show higher 1O2 output than Ti MOFs under 2 W of low-power microwave irradiation due to the narrower band-gap after Mn doping. At the same time, Mn endows the MOFs with a desirable T1 contrast of magnetic resonance imaging (r2/r1 = 2.315). Further, results on HepG2 tumor-bearing mice prove that microwave-triggered Mn-Ti MOFs nearly eradicate the tumors after 14 days of treatment. Our study offers a promising sensitizer for synergistic microwave thermal and microwave dynamic therapy of liver cancer.

Synthesis and biological evaluation of stilbene-based peptoid mimics against the phytopathogenic bacterium Xanthomonas citri pv. citri.

BACKGROUND: The emergence of drug-resistant phytopathogenic bacteria and the need for new types of biological disease-control agents have accelerated efforts toward searching for alternative candidates with a low propensity for resistance development. In this study, a new series of stilbene-based peptoid mimics were synthesized, and their biological activities were evaluated against citrus pathogenic bacteria in vitro and in vivo. RESULTS: Antibacterial bioassay results showed that the dicationic peptoid mimics 9a and 9b displayed excellent bioactivity against Xanthomonas citri pv. citri, with the minimum inhibitory concentration values of 25 µM, which were superior to those of commercial copper biocides Delite (200 µM) and Kasumin Bordeaux (100 µM). In vivo bioassay further confirmed their control efficacy against plant bacterial diseases. In addition, the antibacterial mechanism of action elucidated their membrane-disruption effects resulting in the leakage of the bacterial membranes, which was similar to that of antimicrobial peptides. Moreover, the inhibition effect on biofilm formation of peptoid mimics has also been demonstrated. CONCLUSION: Stilbene-based peptoid mimics synthesized in this study showed promising antibacterial activity with a potent membrane-disruptive mechanism. The results suggested that stilbene-based peptoid mimics have the potential as a candidate new type of bactericide for citrus disease protection.

Self-Assembled Nanoparticles of Symmetrical Cationic Peptide Against Citrus Pathogenic Bacteria.

The increasing drug resistance of phytopathogenic bacteria to conventional bactericides has driven the necessity for exploring new alternatives with a lower tendency to develop bacterial resistance. Here, we report a novel cationic symmetrical peptide P5VP5 (Ac- R+ LI R+ K+ V K+ R+ IL R+ -NH2 that enables self-assembly to form nanoparticles with excellent thermal stability. An in vitro assay showed that P5VP5 nanoparticles exhibited excellent antibacterial activity against Xanthomonas axonopodis pv citri with a MIC value of 20 µM. Meanwhile, under an in planta condition, treatment with peptide nanoparticles demonstrated the highest ability to reduce the development of citrus canker lesions in leaves. Moreover, the nanoparticles could destroy the biofilm formation, damage the cell membranes, and affect the cell membrane permeability, ultimately leading to the death of bacteria. Taken together, these nanoparticles are a promising antibacterial agent that can be used to control citrus canker and other plant diseases caused by bacteria.

Development of self-stratified antibacterial polymers via click chemistry.

An azide-modified long perfluorinated tail quaternary ammonium methacrylate compound (M2) was designed and synthesized. The fluorine containing polyurethane (PU-F) with strong antibacterial properties was prepared via click reaction of M2 and a clickable polymer (PU-Al), which exhibited surface segregation. The PU-F film showed a total kill against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) at an M2 content around 1 wt%. A disk diffusion test confirmed that the ligation efficiency of the antibacterial agents and polymer chains via click chemistry was excellent, and covalent conjugation of the QACs to the polymers prevented leaching.

Click chemistry improved wet adhesion strength of mussel-inspired citrate-based antimicrobial bioadhesives.

For the first time, a convenient copper-catalyzed azide-alkyne cycloaddition (CuAAC, click chemistry) was successfully introduced into injectable citrate-based mussel-inspired bioadhesives (iCMBAs, iCs) to improve both cohesive and wet adhesive strengths and elongate the degradation time, providing numerous advantages in surgical applications. The major challenge in developing such adhesives was the mutual inhibition effect between the oxidant used for crosslinking catechol groups and the Cu(II) reductant used for CuAAC, which was successfully minimized by adding a biocompatible buffering agent typically used in cell culture, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), as a copper chelating agent. Among the investigated formulations, the highest adhesion strength achieved (223.11 ± 15.94 kPa) was around 13 times higher than that of a commercially available fibrin glue (15.4 ± 2.8 kPa). In addition, dual-crosslinked (i.e. click crosslinking and mussel-inspired crosslinking) iCMBAs still preserved considerable antibacterial and antifungal capabilities that are beneficial for the bioadhesives used as hemostatic adhesives or sealants for wound management.

Click Cross-Linking-Improved Waterborne Polymers for Environment-Friendly Coatings and Adhesives.

Waterborne polymers, including waterborne polyurethanes (WPU), polyester dispersions (PED), and polyacrylate emulsions (PAE), are employed as environmentally friendly water-based coatings and adhesives. An efficient, fast, stable, and safe cross-linking strategy is always desirable to impart waterborne polymers with improved mechanical properties and water/solvent/thermal and abrasion resistance. For the first time, click chemistry was introduced into waterborne polymer systems as a cross-linking strategy. Click cross-linking rendered waterborne polymer films with significantly improved tensile strength, hardness, adhesion strength, and water/solvent resistance compared to traditional waterborne polymer films. For example, click cross-linked WPU (WPU-click) has dramatically improved the mechanical strength (tensile strength increased from 0.43 to 6.47 MPa, and Young's modulus increased from 3 to 40 MPa), hardness (increased from 59 to 73.1 MPa), and water resistance (water absorption percentage dropped from 200% to less than 20%); click cross-linked PED (PED-click) film also possessed more than 3 times higher tensile strength (∼28 MPa) than that of normal PED (∼8 MPa). The adhesion strength of click cross-linked PAE (PAE-click) to polypropylene (PP) was also improved (from 3 to 5.5 MPa). In addition, extra click groups can be preserved after click cross-linking for further functionalization of the waterborne polymeric coatings/adhesives. In this work, we have demonstrated that click modification could serve as a convenient and powerful approach to significantly improve the performance of a variety of traditional coatings and adhesives.

Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives.

Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern.

Fluorescence imaging enabled poly(lactide-co-glycolide).

Fluorescent biomaterials have attracted significant research efforts in the past decades. Herein, we report a new series of biodegradable, fluorescence imaging-enabled copolymers, biodegradable photoluminescent poly(lactide-co-glycolide) (BPLP-co-PLGA). Photoluminescence characterization shows that BPLP-co-PLGA solutions, films and nanoparticles all exhibit strong, tunable and stable photoluminescence. By adjusting the molar ratios of L-lactide (LA)/glycolide (GA) and (LA+GA)/BPLP, full degradation of BPLP-co-PLGA can be achieved in 8-16 weeks. The fluorescence decay behavior of BPLP-co-PLGA can be used for non-invasive monitoring of material degradation. In vitro cytotoxicity and in vivo foreign body response evaluations demonstrate that BPLP-co-PLGA exhibits similar biocompatibility to poly(lactide-co-glycolide) (PLGA). The imaging-enabled BPLP-co-PLGA was fabricated into porous scaffolds whose degradation can be monitored through non-invasive imaging and nanoparticles that show theranostic potential demonstrated by fluorescent cellular labeling, imaging and sustained 5-fluorouracil delivery. The development of inherently fluorescent PLGA copolymers is expected to impact the use of already widely accepted PLGA polymers for applications where fluorescent properties are highly desired but limited by the conventional use of cytotoxic quantum dots and photobleaching organic dyes. STATEMENT OF SIGNIFICANCE: This manuscript describes a novel strategy of conferring intrinsic photoluminescence to the widely used biodegradable polymers, poly(lactide-co-glycolide) without introducing any cytotoxic quantum dots or photo-bleaching organic dyes, which may greatly expand the applications of these polymers in where fluorescent properties are highly desired. Given the already significant impact generated by the use of PLGA and alike, this work contributes to fluorescence chemistry and new functional biomaterial design and will potentially generate significant impact on many fields of applications such as tissue engineering, molecular imaging and labeling, and drug delivery.