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ACS Nano Jun 2023The vaccine effect of radiation therapy (RT) has been shown to be limited in both preclinical and clinical settings, possibly due to the inadequacy of RT alone to...
The vaccine effect of radiation therapy (RT) has been shown to be limited in both preclinical and clinical settings, possibly due to the inadequacy of RT alone to stimulate vaccination in immunologically "cold" tumor microenvironments (TMEs) and the mixed effects of RT in promoting tumor infiltration of both effector and suppressor immune cells. To address these limitations, we combined intratumoral injection of the radiated site with IL2 and a multifunctional nanoparticle (PIC). The local injection of these agents produced a cooperative effect that favorably immunomodulated the irradiated TME, enhancing the activation of tumor-infiltrating T cells and improving systemic anti-tumor T cell immunity. In syngeneic murine tumor models, the PIC+IL2+RT combination significantly improved the tumor response, surpassing the single or dual combinations of these treatments. Furthermore, this treatment led to the activation of tumor-specific immune memory and improved abscopal effects. Our findings suggest that this strategy can be used to augment the vaccine effect of RT in clinical settings.
Topics: Humans; Animals; Mice; Interleukin-2; Polylysine; Injections, Intralesional; Neoplasms; CD8-Positive T-Lymphocytes; Antibodies; Vaccination; Nanoparticles; Cell Line, Tumor; Tumor Microenvironment
PubMed: 37216491
DOI: 10.1021/acsnano.3c00418 -
BioMed Research International 2022The study is aimed at investigating the effect of the FLOT2 gene on invasion and metastasis of colorectal cancer (CRC) cells and the corresponding molecular mechanism by...
The study is aimed at investigating the effect of the FLOT2 gene on invasion and metastasis of colorectal cancer (CRC) cells and the corresponding molecular mechanism by preparing polylysine-silicon nanoparticles. Specifically, polylysine was used to modify the silica nanoparticles prepared by the emulsification method to obtain polylysine-silicon nanoparticles. The characterization of polylysine-silicon nanoparticles was completed by nanoparticle size analyzer, laser particle size potentiometer, and transmission microscope. The influence of polylysine-silicon nanoparticles on the survival rate of CRC cell line HT-29 was detected using the method of 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). The FLOT2-siRNA expression vector was constructed and transfected with HT-29. The HT-29 transfected with empty plasmid was used as the negative control (NC). Western Blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect expression levels of FLOT2 gene and epithelial-mesenchymal transition- (EMT-) related genes. Transwell invasion assay, Transwell migration assay, and CCK8 assay were used to detect the cell invasion, migration, and proliferation. The results showed that the average particle size of polylysine-silicon nanoparticles was 30 nm, the potential was 19.65 mV, the particle size was 65.8 nm, and the dispersion coefficient was 0.103. At the same concentration, the toxicity of silicon nanoparticles to HT-29 was significantly lower than that of liposome reagent, and the transfection efficiency was 60%, higher than that of liposome reagent (40%). The mRNA level and protein expression of the FLOT2 gene in the FLOT2-siRNA group were significantly lower than those in the NC group ( < 0.01). The optical density (OD) value of the NC group and the blank control (CK) group were significantly higher than that of FLOT2-siRNA cells ( < 0.01). The OD value of FLOT2-siRNA cells was lower than that of NC cells at 48 h, 72 h, and 96 h ( < 0.01). The mRNA levels and protein expressions of MMP2 and vimentin in the FLOT2-siRNA group were significantly lower than those in the NC group and CK group ( < 0.01). The mRNA level and protein expression of the E-cadherin gene in the FLOT2-siRNA group were significantly higher than those in the NC group and CK group ( < 0.01). In conclusion, an RNA interference plasmid with high transfection efficiency and low cytotoxicity was established based on nanotechnology. siRNA-mediated FLOT2 protein inhibits the invasion, migration, and proliferation of CRC cells by regulating the expression changes of EMT-related genes, which provides a scientific basis for clinical treatment of CRC.
Topics: Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Liposomes; Nanotechnology; Polylysine; RNA Interference; RNA, Messenger; RNA, Small Interfering; Silicon
PubMed: 35419458
DOI: 10.1155/2022/2897338 -
JAMA Network Open May 2020Allergy to β-lactam antibiotics is one of the most frequently reported drug reactions, but epidemiological data in Chinese populations are lacking. Ethnic- and...
IMPORTANCE
Allergy to β-lactam antibiotics is one of the most frequently reported drug reactions, but epidemiological data in Chinese populations are lacking. Ethnic- and region-specific sensitization patterns of skin testing for β-lactam antibiotic allergy are also unknown.
OBJECTIVE
To identify the prevalence, 1-year incidence, and sensitization patterns of β-lactam antibiotic allergy in patients in Hong Kong.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study obtained territorywide, anonymized electronic patient data from the Clinical Management Systems of the Hospital Authority, the sole publicly funded health care system in Hong Kong with facilities in 7 regions (Hong Kong East, Hong Kong West, Kowloon Central, Kowloon East, Kowloon West, New Territories East, and New Territories West). All referrals to Queen Mary Hospital for β-lactam antibiotic allergy testing from January 1, 2018, to December 31, 2019, were also analyzed for sensitization patterns.
MAIN OUTCOMES AND MEASURES
Prevalence and cumulative incidence of β-lactam antibiotic allergy reported in Hong Kong, and sensitization patterns according to β-lactam antibiotic allergy skin testing.
RESULTS
Complete records of 7 184 271 unique patients were analyzed, with a men to women ratio of 1:1.2 and with a median age of 44 years. The prevalence of physician-reported β-lactam antibiotic allergy was 2.0%, and the cumulative incidence was 107 per 100 000 population. Of the 34 402 new drug allergies reported in 2018, 8032 (23.3%) were β-lactam antibiotic allergies. Three hundred fifty-five patients with reactions suggestive of β-lactam antibiotic allergy underwent skin testing, and only 49 (13.8%; 95% CI, 10.64%-17.90%) of them had positive test results. Of these 49 patients, 14 (28.6%; 95% CI, 18.35%-44.49%) had selective reaction and 35 (71.4%; 95% CI, 59.84%-85.27%) had nonselective reaction. The sensitization rate to either benzylpenicilloyl polylysine or a minor determinant (benzylpenicilloate) was 47.0% (n = 23; 95% CI, 34.85%-63.21%), with 10 patients monosensitized to benzylpenicilloyl polylysine only (20.4%; 95% CI, 11.74%-35.48%) and 5 to benzylpenicilloate only (10.2%; 95% CI, 4.45%-23.42%).
CONCLUSIONS AND RELEVANCE
Results of this study suggest that patients in Hong Kong with β-lactam antibiotic allergy had much higher rates of monosensitization to benzylpenicilloyl polylysine and benzylpenicilloate, making these reagents essential in β-lactam antibiotic skin tests. Such a finding warrants future studies into whether this sensitization is specific to ethnicity or region.
Topics: Adult; Anti-Bacterial Agents; Asian People; Cross-Sectional Studies; Demography; Drug Hypersensitivity; Female; Hong Kong; Humans; Incidence; Male; Prevalence; Skin Tests; beta-Lactams
PubMed: 32374398
DOI: 10.1001/jamanetworkopen.2020.4199 -
Pharmaceutics Dec 2020Physiological wound healing process can be delayed in the presence of certain pathologies, such as diabetes or cancer. In this perspective, the aim of this study was to...
Physiological wound healing process can be delayed in the presence of certain pathologies, such as diabetes or cancer. In this perspective, the aim of this study was to design a new nanogel platform of hyaluronan, poly-L-lysine and berberine suitable for wound treatment. Two different nanogel formulations were selected after a first formulation screening. They were prepared by adding dropwise 2 mg/mL hyaluronan aqueous solution (200 or 700 kDa) to 1.25 mg/mL poly-L-lysine aqueous solution. Blank nanogels formulated with 200 kDa HA resulted stable after freeze-drying with dimensions, polydispersity index and zeta potential of 263.6 ± 13.1 nm, 0.323 ± 0.029 and 32.7 ± 3.5 mV, respectively. Both blank and berberine-loaded nanogels showed rounded-shape structures. Loaded nanogels released nearly 50% of loaded berberine within 45 min, whereas the remaining 50% was released up to 24 h in vitro. Both, blank and berberine-loaded nanogels were able to completely close the fibroblasts gap in 42 h.
PubMed: 33379303
DOI: 10.3390/pharmaceutics13010034 -
Langmuir : the ACS Journal of Surfaces... Sep 2022The DNA origami technique allows the precise synthesis of complex, biocompatible nanomaterials containing small molecules, biomolecules, and inorganic nanoparticles. The...
The DNA origami technique allows the precise synthesis of complex, biocompatible nanomaterials containing small molecules, biomolecules, and inorganic nanoparticles. The negatively charged phosphates in the backbone make DNA highly water-soluble and require salts to shield its electrostatic repulsion. DNA origamis are therefore not soluble in most organic solvents. While this is not problematic for applications in biochemistry, biophysics, or nanomedicine, other potential applications, processes, and substrates are incompatible with saline solutions, which include the synthesis of many nanomaterials, and reactions in templated synthesis, the operation of nanoelectronic devices, or semiconductor fabrication. To overcome this limitation, we coated DNA origami with amphiphilic poly(ethylene glycol) polylysine block copolymers and transferred them into various organic solvents including chloroform, dichloromethane, acetone, or 1-propanol. Our approach maintains the shape of the nanostructures and protects functional elements bound to the structure, such as fluorophores, gold nanoparticles, or proteins. The DNA origami polyplex micellization (DOPM) strategy hence enables solubilization or a phase transfer of complex structures into various organic solvents, which significantly expands the use of DNA origami for a range of potential applications and technical processes.
Topics: 1-Propanol; Acetone; Chloroform; DNA; Gold; Metal Nanoparticles; Methylene Chloride; Nanostructures; Phosphates; Polyethylene Glycols; Polylysine; Polymers; Salts; Solubility; Solvents; Water
PubMed: 36103620
DOI: 10.1021/acs.langmuir.2c01508 -
BMJ Open Quality Jul 2022Patients with self-reported antibiotic allergies have a higher cost of care, more frequent infections with resistant bacteria and worse health outcomes than patients...
BACKGROUND
Patients with self-reported antibiotic allergies have a higher cost of care, more frequent infections with resistant bacteria and worse health outcomes than patients without antibiotic allergies. Ultimately, less than 5% of patients who report a penicillin allergy have a clinically significant immune-mediated hypersensitivity reaction when tested. As 10%-30% of the population of pregnant patients are colonised for group B (GBS) and guidelines recommend penicillin as the treatment of choice for GBS, current recommendations support penicillin allergy testing in pregnant patients who report an allergy.
METHODS AND INTERVENTION
In this quality improvement project, nursing staff used an algorithm outlining inclusion and exclusion criteria to determine which patients were eligible to have penicillin allergy testing completed. Penicillin allergy testing consisted of a skin test using benzylpenicilloyl polylysine (Pre-Pen), penicillin G potassium, amoxicillin and alkaline hydrolysis mix (penicilloate) as a prick skin test, followed by intradermal skin test and finally an oral challenge with either amoxicillin or penicillin. Patient outcomes were analysed to evaluate the impact of the intervention.
RESULTS
Of the 1266 patients receiving prenatal care during the intervention, 236 (19%) reported a history of penicillin allergy, and 212 if these were eligible for testing. 150 of the eligible patients were offered penicillin allergy testing. 101 patients (67%) completed testing and 49 (33%) declined testing. Seven patients (7%) had positive penicillin allergy testing, while 94 patients (93%) had negative penicillin allergy testing and were immediately de-labelled as penicillin allergic. Seventeen of the de-labelled patients subsequently tested positive for GBS colonisation, and all received intrapartum penicillin without adverse events.
CONCLUSIONS
Pursuing penicillin allergy testing for pregnant patients with reported penicillin allergy is a safe and feasible approach, allowing for allergy de-labelling and safe, guideline-driven antimicrobial therapy during subsequent labour and delivery hospitalisations. Cost-effectiveness of the allergy testing and impact on later episodes of care should be further investigated.
Topics: Amoxicillin; Anti-Bacterial Agents; Drug Hypersensitivity; Female; Humans; Penicillins; Pregnancy; Skin Tests
PubMed: 35906008
DOI: 10.1136/bmjoq-2022-001859 -
Frontiers in Bioengineering and... 2022Cellulose-based functional composite films can be a good substitute for conventional plastic packaging to ensure food safety. In this study, the semi-transparent,...
Cellulose-based functional composite films can be a good substitute for conventional plastic packaging to ensure food safety. In this study, the semi-transparent, mechanical strengthened, UV-shielding, antibacterial and biocompatible films were developed from hydroxyethyl cellulose Polyvinyl alcohol (PVA) and ε-polylysine (ε-PL) were respectively used as reinforcing agent and antibacterial agent, and chemical cross-linking among these three components were constructed using epichlorohydrin The maximum tensile strength and elongation at break were 95.9 ± 4.1 MPa and 148.8 ± 2.6%, respectively. TG-FTIR and XRD analyses indicated that chemical structure of the composite films could be well controlled by varying component proportion. From UV-Vis analysis, the optimum values of the percentage of blocking from UV-A and UV-B and ultraviolet protection factor values were 98.35%, 99.99% and 60.25, respectively. Additionally, the composite films exhibited good water vapor permeability, swelling behavior, antibacterial activity and biocompatibility. In terms of these properties, the shelf life of grapes could be extended to 6 days after packing with the composite film.
PubMed: 36246371
DOI: 10.3389/fbioe.2022.989893 -
Frontiers in Nutrition 2024This study investigated the effects of nisin combined with ε-polylysine on microorganisms and the refrigerated quality of fresh-cut jackfruit. After being treated with...
This study investigated the effects of nisin combined with ε-polylysine on microorganisms and the refrigerated quality of fresh-cut jackfruit. After being treated with distilled water (control), nisin (0.5 g/L), ε-polylysine (0.5 g/L), and the combination of nisin (0.1 g/L) and ε-polylysine (0.4 g/L), microporous modified atmosphere packaging (MMAP) was carried out and stored at 10 ± 1°C for 8 days. The microorganisms and physicochemical indexes were measured every 2 days during storage. The results indicated that combined treatment (0.1 g/L nisin, 0.4 g/L ε-polylysine) had the best preservation on fresh-cut jackfruit. Compared with the control, combined treatment inhibited microbial growth (total bacterial count, mold and yeast), reduced the weight loss rate, respiratory intensity, polyphenol oxidase and peroxidase activities, and maintained higher sugar acid content, firmness, and color. Furthermore, it preserved higher levels of antioxidant compounds, reduced the accumulation of malondialdehyde and hydrogen peroxide, thereby reducing oxidative damage and maintaining high nutritional and sensory qualities. As a safe application of natural preservatives, nisin combined with ε-polylysine treatment has great application potential in the fresh-cut jackfruit industry.
PubMed: 38419851
DOI: 10.3389/fnut.2024.1299810 -
Theranostics 2020Both spatial accuracy and temporal persistence are crucial in drug delivery, especially for anti-tumor intravenous nanomedicines, which have limited persistence due to...
Both spatial accuracy and temporal persistence are crucial in drug delivery, especially for anti-tumor intravenous nanomedicines, which have limited persistence due to their small particle sizes and easy removal from tumors. The present study takes advantage of morphological transformation strategy to regulate intravenous nanomedicines to display different sizes in different areas, achieving high efficient enrichment and long retention in lesions. We designed and synthesized functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) consisting of self-assembled doxorubicin-peptide conjugates (DPCs) and an acidic-responsive shielding layer named the functional polylysine graft (FPG), which can regulate the assembly morphology of the DPCs from spherical DPC nanoparticles (DPC-NPs) to DPC-nanofibers (DPC-NFs) by preventing the assembly force from π-π stacking and hydrogen bond between the DPC-NPs. The morphology transformation and particle changes of FDPC-NPs in different environments were determined with DLS, TEM and SEM. We used FRET to explore the enhanced retention effect of FDPC-NPs in tumor site . HPLC-MS/MS analytical method was established to analyze the biodistribution of FDPC-NPs in H22 hepatoma xenograft mouse model. Finally, the antitumor effect and safety of FDPC-NPs was evaluated. The FDPC-NPs were stable in blood circulation and responsively self-assembled into DPC-NFs when the FDPC-NPs underwent the acid-sensitive separation of the shielding layer in a mildly acidic microenvironment. The FDPC-NPs maintained a uniform spherical size of 80 nm and exhibited good morphological stability in neutral aqueous solution (pH 7.4) but aggregated into a long necklace-like chain structure or a crosslinked fiber structure over time in a weakly acidic solution (pH 6.5). These acidity-triggered transformable FDPC-NPs prolonged the accumulation in tumor tissue for more than 5 days after a single injection and improved the relative uptake rate of doxorubicin in tumors 31-fold. As a result, FDPC-NPs exhibited a preferable anti-tumor efficacy and a reduced side effect compared with free DOX solution and DOX liposomes. Morphology-transformable FDPC-NPs represent a promising therapeutic approach for prolonging the residence time of drugs at the target site to reduce side effect and enhance therapeutic efficacy. Our studies provide a new and simple idea for the design of long-term delivery systems for intravenous chemotherapeutic drugs.
Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Doxorubicin; Drug Carriers; Drug Liberation; Drug Stability; Humans; Hydrogen-Ion Concentration; Mice; Nanoparticles; Neoplasms; Particle Size; Peptides; Polylysine; Tandem Mass Spectrometry; Tissue Distribution
PubMed: 32724464
DOI: 10.7150/thno.45088 -
Journal of Controlled Release :... Dec 2023Adipose-derived mesenchymal stem cell-derived small extracellular vesicles (Ad-MSC-sEVs/AMEs) combined with scaffold materials are used in tissue-engineered bladders;...
Negatively charged bladder acellular matrix loaded with positively charged adipose-derived mesenchymal stem cell-derived small extracellular vesicles for bladder tissue engineering.
Adipose-derived mesenchymal stem cell-derived small extracellular vesicles (Ad-MSC-sEVs/AMEs) combined with scaffold materials are used in tissue-engineered bladders; however, the lack of retention leads to limited distribution of AMEs in the scaffold areas and low bioavailability of AMEs after bladder reconstruction. To improve retention of AMEs, we developed a novel strategy that modifies the surface charge of the bladder acellular matrix (BAM) via oxidative self-polymerization of dopamine-reducing graphene oxide (GO) and AMEs using ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD). We evaluated two BAM surface modification methods and evaluated the biocompatibility of materials and PPD and electrostatic adherence effects between PPD-modified AMEs and rGO-PDA/BAM in vivo and in vitro. Surface modification increased retention of AMEs, enhanced regeneration of bladder structures, and increased electrical conductivity of rGO-PDA/BAM, thereby improving bladder function recovery. RNA-sequencing revealed 543 miRNAs in human AMEs and 514 miRNAs in rat AMEs. A Venn diagram was used to show target genes of miRNA with the highest proportion predicted by the four databases; related biological processes and pathways were predicted by KEGG and GO analyses. We report a strategy for improving bioavailability of AMEs for bladder reconstruction and reveal that enriched miR-21-5p targets PIK3R1 and activates the PI3K/Akt pathway to promote cell proliferation and migration.
Topics: Rats; Humans; Animals; Tissue Engineering; Urinary Bladder; Phosphatidylinositol 3-Kinases; Extracellular Matrix; Mesenchymal Stem Cells; MicroRNAs; Extracellular Vesicles
PubMed: 37944669
DOI: 10.1016/j.jconrel.2023.10.048