Biofilm microenvironment activated supramolecular nanoparticles for enhanced photodynamic therapy of bacterial keratitis
Infectious keratitis caused by bacterial biofilms is one of the main causes of corneal blindness, presenting a serious threat to public health. In this study, matrix metalloproteinase (MMP)-sensitive supramolecular nanoparticles (denoted as MMP-S NPs) were constructed for enhancing photodynamic antibacterial effect against biofilm-associated bacterial keratitis. MMP-S NPs were prepared by host-guest self-assembly of chlorin e6 (Ce6) conjugated β-cyclodextrin (β-CD) prodrug (β-CD-Ce6) and MMP-9-sensitive peptides (YGRKKKRRQRRR-GPLGVRG-EEEEEE) terminated with adamantane (ad) (ad-MMP-S PEPs). MMP-S NPs with EEEEEE peptide shell had a negatively charged surface, preventing adhesion to the normal ocular surface or healthy corneal cells, thus enhancing tear retention time. After arriving at the infected lesions, the protective EEEEEE peptide shell of MMP-S NPs was removed, triggered by overexpressed MMP-9 in the keratitis microenvironment. The subsequently exposed cationic peptides helped the nanoparticles penetrate and accumulate in biofilms as well as bind to gram-negative bacteria Pseudomonas aeruginosa (P. aeruginosa), which eventually improved the photodynamic antibacterial effect. Furthermore, the P. aeruginosa keratitis model verified the high effectiveness of a topical eye drop formulation of MMP-S NPs in killing bacteria by destroying the bacterial membrane as a result of in situ photodynamic activation of reactive oxygen species (ROS) formation under light irradiation. Moreover, the inflammatory response in the cornea was inhibited to a great extent. As a result, further damage to the corneal tissue was completely suppressed. This research provides a viable antibacterial alternative to fight against bacterial keratitis through effective elimination of infectious bacteria and eradication of bacterial biofilms in the cornea
HAN, Haijie et al. Biofilm microenvironment activated supramolecular nanoparticles for enhanced photodynamic therapy of bacterial keratitis. Journal of Controlled Release, 2020.
Tannic acid-functionalized boron nitride nanosheets for theranostics
Here, we report a tannic acid-Fe3+ coordination complex coating that confers magnetic resonance imaging (MRI) theranostic properties to inert nanomaterials. Boron nitride nanosheets (BNS), which lack magnetic field and light responsiveness, were used as a model nonfunctional nanomaterial. Among various catechol derivatives tested (i.e., dopamine, 3,4-dihydroxyphenylacetic acid, gallic acid, and tannic acid), a coating of tannic acid-Fe3+ coordination complex provided the highest magnetic field relaxivity and near infrared (NIR) laser light responsiveness. An in vitro study showed that KB tumor cells treated with tannic acid-Fe3+ coordination complex adsorbed on BNS (TA-Fe/BNS) exhibited higher T1-weighted magnetic resonance contrast compared with plain BNS, and BNS coated with tannic acid or Fe alone. NIR irradiation at 808 nm caused a significant increase in KB tumor cell death after treatment with TA-Fe/BNS compared with other treatments. In vivo MRI imaging revealed tumor accumulation of intravenously administered TA-Fe/BNS. Guided by MRI information, application of focused laser irradiation onto tumor tissues resulted in complete tumor ablation. These results support the potential of TA-Fe/BNS for MRI theranostics. Moreover, this study suggests the wide applicability of TA-Fe noncovalent coating as biocompatible and facile tool for converting nonfunctional early-generation nanomaterials into functional new nanomaterials, opening new opportunities for their use in translational biomedical applications such as MRI theranostics.
GAYONG, Shim et al. Tannic acid-functionalized boron nitride nanosheets for theranostics. Journal of Controlled Release, 2020.
Implant-based direction of magnetic nanoporous silica nanoparticles - influence of macrophage depletion and infection
Implant associated infections are still key problem in surgery. In the present study, the combination of a magnetic implant with administered magnetic nanoporous silica nanoparticles as potential drug carriers was examined in mice in dependence of local infection and macrophages as influencing factors. Four groups of mice (with and without implant infection and with and without macrophage depletion) received a magnet on the left and a titanium control on the right hind leg. Then, fluorescent nanoparticles were administered and particle accumulations at implant surfaces and in inner organs as well as local tissue reactions were analyzed. Magnetic nanoparticles could be found at the surfaces of magnetic implants in different amounts depending on the treatment groups and only rarely at titanium surfaces. Different interactions of magnetic implants, particles, infection and surrounding tissues occurred. The general principle of targeted accumulation of magnetic nanoparticles could be proven.
REIFENRATH, Janin et al. Implant-based direction of magnetic nanoporous silica nanoparticles-influence of macrophage depletion and infection. Nanomedicine: Nanotechnology, Biology and Medicine, p. 102289, 2020.
Cloxacillin nanostructured formulation for the treatment of bovine keratoconjunctivitis
Infectious bovine keratoconjunctivitis (IBK) is a widespread, contagious ocular disease that affects cattle, especially dairy breeds. The disease is caused by Gram-negative bacteria mainly Moraxella bovis, and its treatment consists of parenteral or topic antibiotic therapy. The topic treatment approach is used more commonly in lactating cows, to avoid milk disposal. However, treatment failures are common, because the antibiotic is removed during lacrimation. This study aimed to evaluate the susceptibility of commercial cloxacillin and evaluate the efficacy of nanostructured cloxacillin in clinical cases of IBK by Moraxella. The minimum inhibitory concentration (MIC) of nanoparticle cloxacillin nanocoated, the nanoparticle without the antibiotic and the commercial cloxacillin were determined in vitro with field samples of Moraxella ovis (5) and Moraxella bovis (5). The efficiency of nanoparticles was tested in three cows naturally infected that were treated with 1.0 mL (with 0.32 mg of nanostructured cloxacillin) for the ocular route. Moraxella bovis was isolated and identified by biochemical and molecular methods before the treatment. The animals were treated every 12 h for six days. The cure was considered by the absence of clinical symptoms and bacteria after treatment. The mucoadhesive nanoparticle-based formulation promoted clinical cure with a low number of doses of antibiotics, probably due to the maintenance of the MIC in the ocular mucosa for longer due to the mucoadhesive characteristics of the nanoparticle. The results indicate that the use of nanocoated cloxacillin is possible to control infectious bovine keratoconjunctivitis.
FONSECA, Miriam das Dores Mendes et al. Cloxacillin nanostructured formulation for the treatment of bovine keratoconjunctivitis. Veterinary and Animal Science, v. 9, p. 100089, 2020.
Using chitosan microparticles to treat metritis in lactating dairy cows
The main objective of this study was to evaluate the efficacy of intrauterine administration of chitosan microparticles (CM) in curing metritis in dairy cows. A secondary objective was to evaluate the effects of metritis treatments on milk yield, survival, and reproductive performance. Cows with a fetid, watery, red-brownish vaginal discharge were diagnosed with metritis. Holstein cows (n = 826) with metritis from 3 dairies located in northern Florida were blocked by parity (primiparous or multiparous) and, within each block, randomly assigned to one of 3 treatments: CM (n = 276) = intrauterine infusion of 24 g of CM dissolved in 40 mL of sterile distilled water at the time of metritis diagnosis (d 0), 2 (d 2), and 4 (d 4) d later; ceftiofur (CEF; n = 275) = subcutaneous injection of 6.6 mg/kg ceftiofur crystalline-free acid in the base of the ear at d 0 and d 3; Control (CON; n = 275) = no treatment applied at metritis diagnosis. All groups could receive escape therapy if condition worsened. Cure was considered when vaginal discharge became mucoid and not fetid. A group of nonmetritic (NMET; n = 2,436) cows was used for comparison. Data were analyzed by generalized linear mixed and Cox's proportional hazard models. Cows in CM and CON had lesser risk of metritis cure on d 12 than cows in CEF (58.6 ± 5.0 vs. 61.9 ± 4.9% vs. 77.9 ± 3.9, respectively). The proportion of cows culled within 60 days in milk (DIM) was greater for cows in CM than for cows in CEF and CON (21.5 ± 2.7 vs. 9.7 ± 1.9 vs. 11.3 ± 2.0%, respectively). Treatment did not affect rectal temperature or plasma nonesterified fatty acids, β-hydroxybutyrate, and haptoglobin concentrations. Milk yield in the first 60 DIM differed for all treatments, and it was lowest for CM (35.8 ± 0.3 kg/d), followed by CON (36.8 ± 0.3 kg/d) and CEF (37.9 ± 0.3 kg/d). The hazard of pregnancy up to 300 DIM was lesser for CM than CEF (hazard ratio = 0.62; 95% CI: 0.50–0.76), for CM than CON (hazard ratio = 0.77; 95% CI: 0.62–0.95) and for CON than CEF (hazard ratio = 0.80; 95% CI: 0.65–0.99). Culling was greater, and milk yield and fertility were lesser for CEF than NMET. In summary, CM did not improve the cure of metritis, and was detrimental to milk yield, survival, and fertility compared with CON. In contrast, CEF increased the cure of metritis, milk yield, and fertility compared with CM and CON. Finally, the negative effects of metritis on milk yield culling and fertility could not be completely reversed by CEF.
DE OLIVEIRA, E. B. et al. Using chitosan microparticles to treat metritis in lactating dairy cows. Journal of Dairy Science, 2020.
Topical siRNA delivery to anterior eye using novel hybrid silicon-lipid nanoparticle delivery system
The major unmet need and crucial challenge hampering the exciting potential of RNAi therapeutics in ophthalmology is to find an effective, safe and non-invasive means of delivering siRNA to the cornea. Although all tissues of the eye are accessible by injection, topical application is preferable for the frequent treatment regimen that would be necessary for siRNA-induced gene silencing. However, the ocular surface is one of the more complex biological barriers for drug delivery due to the combined effect of short contact time, tear dilution and poor corneal cell penetration. Using nanotechnology to overcome the challenges, we developed a unique silicon-based delivery platform for ocular delivery of siRNA. This biocompatible hybrid of porous silicon nanoparticles and lipids has demonstrated an ability to bind nucleic acid and deliver functional siRNA to corneal cells both in vitro and in vivo. Potent transfection of human corneal epithelial cells with siRNA-ProSilic® formulation was followed by a successful downregulation of reporter protein expression. Moreover, siRNA complexed with this silicon-based hybrid and applied in vivo topically to mice eyes penetrated across all cornea layers and resulted in a significant reduction of the targeted protein expression in corneal epithelium. In terms of siRNA loading capacity, system versatility, and potency of action, ProSilic provides unique attributes as a biodegradable delivery platform for therapeutic oligonucleotides.
BARAN-RACHWALSKA, Paulina et al. Topical siRNA delivery to anterior eye using novel hybrid silicon-lipid nanoparticle delivery system. Journal of Controlled Release, 2020.
Co-delivery of Peptide Neoantigens and Stimulator of Interferon Genes Agonists Enhances Response to Cancer Vaccines
Cancer vaccines targeting patient-specific neoantigens have emerged as a promising strategy for improving responses to immune checkpoint blockade. However, neoantigenic peptides are poorly immunogenic and inept at stimulating CD8+ T cell responses, motivating a need for new vaccine technologies that enhance their immunogenicity. The stimulator of interferon genes (STING) pathway is an endogenous mechanism by which the innate immune system generates an immunological context for priming and mobilizing neoantigen-specific T cells. Owing to this critical role in tumor immune surveillance, a synthetic cancer nanovaccine platform (nanoSTING-vax) was developed that mimics immunogenic cancer cells in its capacity to efficiently promote co-delivery of peptide antigens and the STING agonist, cGAMP. The co-loading of cGAMP and peptides into pH-responsive, endosomolytic polymersomes promoted the coordinated delivery of both cGAMP and peptide antigens to the cytosol, thereby eliciting inflammatory cytokine production, co-stimulatory marker expression, and antigen cross-presentation. Consequently, nanoSTING-vax significantly enhanced CD8+ T cell responses to a range of peptide antigens. Therapeutic immunization with nanoSTING-vax, in combination with immune checkpoint blockade, inhibited tumor growth in multiple murine tumor models, even leading to complete tumor rejection and generation of durable antitumor immune memory. Collectively, this work establishes nanoSTING-vax as a versatile platform for enhancing immune responses to neoantigen-targeted cancer vaccines.
SHAE, Daniel et al. Co-Delivery of Peptide Neoantigens and Stimulator of Interferon Genes (STING) Agonists Enhances Response to Cancer Vaccines. ACS nano, 2020.
Ionic liquid-mediated delivery of insulin to buccal mucosa
Buccal drug delivery offers a potential non-invasive means of delivering therapeutics to patients. Despite the promise, the feasibility of transporting proteins and peptides into systemic circulation from buccal administration remains a daunting challenge. Here, we report the fabrication of a biodegradable polymeric patch for buccal delivery of insulin using chitosan as the mucoadhesive matrix and ionic liquids (ILs)/deep eutectic solvent (DES) as the transport facilitator. Insulin is mixed with ILs/DES made from Choline and Geranic acid (CAGE) to form a viscoelastic CAGE gel and sandwiched between two layers of a biodegradable polymer. The rheological properties of the CAGE gel were dominated by the elastic modulus and suggested a solid-like viscoelastic behavior. CAGE induced a 7-fold increase in the cumulative insulin transport across the ex vivo porcine buccal tissue (~26% of loaded insulin) which was also confirmed by confocal microscopy. The CAGE/insulin patches placed in the rat buccal pouch in vivo lowered blood glucose levels in a dose-dependent manner (up to 50% drop recorded) with no obvious tissue damage at the application site. The pharmacokinetic performance of the delivered insulin indicated a sustained profile as serum insulin levels plateaued after 3 h for the duration of study. The safety and efficacy of the polymeric patch using insulin as a model drug holds significant promise as a platform technology to deliver injectables through the buccal route.
VAIDYA, A. and MITRAGOTRI, S. Ionic liquid-mediated delivery of insulin to buccal mucosa. Journal of Controlled Release, 2020.
Delivery of a model lipophilic membrane cargo to bone marrow via cell-derived microparticles
Bone marrow (BM) is the central immunological organ and the origin of hematological diseases. Efficient and specific drug delivery to the BM is an unmet need. We tested delivery of fluorescent indocarbocyanine lipids (ICLs, DiR, DiD, DiI) as a model lipophilic cargo. Systemically injected T-lymphocyte cell line Jurkat delivered ICLs to the BM more efficiently than erythrocytes, and more selectively than PEGylated liposomes. Near infrared imaging showed that the delivery was restricted to the BM, lungs, liver and spleen, with no accumulation in the kidneys, brain, heart, intestines, fat tissue and pancreas. Following systemic injection of ICL-labeled cells in immunodeficient or immunocompetent mice, few cells arrived in the BM intact. However, between 5 and 10% of BM cells were ICL-positive. Confocal microscopy of intact BM confirmed that ICLs are delivered independently of the injected cells. Flow cytometry analysis showed that the lipid accumulated in both CD11b + and CD11b- cells, and in hematopoietic progenitors. In a xenograft model of acute myeloid leukemia, a single injection of 10 million Jurkat cells delivered DiD to ~15% of the tumor cells. ICL-labeled cells disappeared from blood almost immediately post-intravenous injection, but numerous cell-derived microparticles continued to circulate in blood. The microparticle particle formation was not due to the ICL labeling or complement attack and was observed after injection of both syngeneic and xenogeneic cells. Injection of microparticles produced in vitro from Jurkat cells resulted in a similar ICL delivery as the injection of intact Jurkat cells. Our results demonstrate a novel delivery paradigm wherein systemically injected cells release microparticles that accumulate in the BM. In addition, the results have important implications for studies involving systemically administered cell therapies.
YANG, Chunyan et al. Delivery of a model lipophilic membrane cargo to bone marrow via cell-derived microparticles. Journal of Controlled Release, 2020.
Cold plasma combined with liposomal ethanolic coconut husk extract: A potential hurdle technology for shelf-life extension of Asian sea bass slices packaged under modified atmosphere
The influence of cold plasma (CP) generated using the mixed gases (oxygen, carbon dioxide argon: 10: 60:30) for 5 min in combination with ethanolic coconut husk extract (ECHE) in either free or liposomal encapsulated form (LE-ECHE) at a concentration of 400 ppm on shelf-life of refrigerated Asian sea bass slices (ASBS) packaged under modified atmosphere was studied.
LE-ECHE was prepared using 60 μmol/ml lipid phase containing soybean phosphatidylcholine/cholesterol mixture (4:1, mol ratio) and 1% ECHE. ECHE or LE-ECHE were dissolved in a minimum volume of water and mixed with Asian seabass slices to obtain the final concentration of 400 ppm. Total viable mesophilic bacteria count in CP treated ASBS, particularly those enriched with ECHE or LE-ECHE (EC400-CP and LEC400-CP, respectively) were at least 1 log CFU/g lower than that of the control. Protein and lipid oxidation were lower in EC400-CP and LEC400-CP as compared to those treated with CP only. Discoloration of slices mediated by ECHE was solved by encapsulating ECHE in liposome. Therefore, CP combined with LE-ECHE, was an effective hurdle approach for shelf-life extension of ASBS for more than 18 days at 4 °C.
OLATUNDE, Oladipupo Odunayo; BENJAKUL, Soottawat; VONGKAMJAN, Kitiya. Cold plasma combined with liposomal ethanolic coconut husk extract: A potential hurdle technology for shelf-life extension of Asian sea bass slices packaged under modified atmosphere. Innovative Food Science & Emerging Technologies, p. 102448, 2020.
Carbon dots from dragonfruit peels as growth-enhancer on ipomoea aquatica vegetable cultivation
C-dots have been successfully synthesised from the dragon fruit peels and were applied as growth-enhancer for Ipomoea aquatica vegetable cultivation. C-dots were obtained from the extract of dragon fruit peels via microwave radiation for 5 to 30 min. Two typical peaks of betalains in the dragon fruit peel extract experienced alteration. When increasing the microwave radiation time, typical peak intensity at 543 nm is decreased and peak intensity at 393 nm is increased. C-dots from dragon fruit peels have particle size in range of 8–25 nm. The optimum C-dots have been produced from 20-min microwave radiation with power of 230 watt. The emission of C-dots appeared at wavelength of 450 nm. The obtained C-dots are capable of binding nitrogen-phosphor-potassium (NPK) fertiliser and act as nutrients carrier. C-dots were then directly supplemented to Ipomoea aquatica vegetable to figure out their influence on plant growth. The supplementation of C-dots was varied by their volume fraction. The effect of C-dots was analysed by measuring the growth rate of plant. This study confirmed that the supplementation of C-dots could enhance the growth of Ipomoea aquatica vegetable. This study denoted that C-dots from dragon fruit peel extracts successfully act as a growth enhancer to increase vegetable yields.
AJI, Mahardika Prasetya et al. Carbon dots from dragonfruit peels as growth-enhancer on ipomoea aquatica vegetable cultivation. Advances in Natural Sciences: Nanoscience and Nanotechnology, v. 11, n. 3, p. 035005, 2020.
Polyethylenimine-functionalized polyacrylonitrile anion exchange fiber as a novel adsorbent for rapid removal of nitrate from wastewater
The development of an adsorbent with high adsorption ability and favorable cyclic regeneration performance for the removal of nitrate residues from wastewater is a task of vital importance. To this end, polyacrylonitrile fiber (PANF) was modified with polyethyleneimine (PEI), and alkyl groups were then introduced around the active amine groups to prepare three polymer-based anion exchange fibers (PAN-PEI-3C, PAN-PEI-5C, and PAN-PEI-8C). The novel fibers were characterized using techniques such as scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The adsorption isotherms of the fibers were best fitted by the Langmuir model, and PAN-PEI-5C exhibited a higher adsorption amount of nitrate (31.32 mg/g) than the other adsorbents. The equilibrium was reached expeditiously (within 10 min), and both pseudo-first-order and pseudo-second-order models could well describe the adsorption kinetics. More attractively, the saturated PAN-PEI-5C could be eluted using a low-concentration (0.3 M) NaCl solution, without any sharp loss of adsorption amount for five consecutive cycles in the presence of dissolved organic matter (DOM). Furthermore, PAN-PEI-5C could effectively adsorb low-concentration nitrate from real secondary effluents in a fixed-bed column experiment. Our work provides a promising and low-cost material for the removal of nitrate residues in practical applications.
SUN, Yue; ZHENG, Weisheng. Polyethylenimine-functionalized polyacrylonitrile anion exchange fiber as a novel adsorbent for rapid removal of nitrate from wastewater. Chemosphere, p. 127373, 2020.