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1.
Plants (Basel) ; 13(2)2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38256791

ABSTRACT

A better understanding of the factors that reduce bundle-sheath cell leakage to CO2 (Փ), enhance 13C carbon isotope discrimination, and enhance the photosynthetic capacity of barley leaves will be useful to develop a nutrient- and water-saving strategy for dry-land farming systems. Therefore, barley plants were exposed to a novel nitrification inhibitor (NI) (3,4-dimethyl-1H-pyrazol-1-yl succinic acid) (DMPSA) and a urease inhibitor (UI) (N-butyl thiophosphorictriamide (NBPT)) with mulched drip fertigation treatments, which included HF (high-drip fertigation (370 mm) under a ridge furrow system), MF (75% of HF, moderate-drip fertigation under a ridge furrow system), LF (50% of HF, low-drip fertigation under a ridge furrow system), and TP (traditional planting with no inhibitors or drip fertigation strategies). The results indicated that the nitrification inhibitor combined with mulched drip fertigation significantly reduced bundle-sheath cell leakage to CO2 (Փ) as a result of increased soil water content; this was demonstrated by the light and CO2 response curves of the photosynthesis capacity (An), the apparent quantum efficiency (α), and the 13C-photosynthate distribution. In the inhibitor-based strategy, the use of the urease and nitrification inhibitors reduced Փ by 35% and 39% compared with TP. In the NI-HF strategy, it was found that barley could retain the maximum photosynthesis capacity by increasing the leaf area index (LAI), An, rubisco content, soluble protein, dry matter per plant, and productivity. The CO2 and light response curves were considerably improved in the NI-HF and NI-MF treatments due to a higher 13C carbon isotope (Δ‱), respiration rate (Rd), and Ci/Ca, therefore obtaining the minimum Փ value. With both inhibitors, there was a significant difference between HF and LF drip fertigation. The NI-MF treatment significantly increased the grain yield, total chlorophyll content, WUE, and NUE by 52%, 47%, 57%, and 45%, respectively. Collectively, the results suggest that the new nitrification inhibitor (DMPSA) with HF or MF mulched drip fertigation could be promoted in semi-arid regions in order to mitigate bundle-sheath cell leakage to CO2 (Փ), without negatively affecting barley production and leading to the nutrient and water use efficiency of barley.

2.
ACS Nano ; 17(22): 22901-22915, 2023 11 28.
Article in English | MEDLINE | ID: mdl-37939210

ABSTRACT

Intestinal epithelium undergoes regeneration after injuries, and the disruption of this process can lead to inflammatory bowel disease and tumorigenesis. Intestinal stem cells (ISCs) residing in the crypts are crucial for maintaining the intestinal epithelium's homeostasis and promoting regeneration upon injury. However, the precise role of DGCR8, a critical component in microRNA (miRNA) biogenesis, in intestinal regeneration remains poorly understood. In this study, we provide compelling evidence demonstrating the indispensable role of epithelial miRNAs in the regeneration of the intestine in mice subjected to 5-FU or irradiation-induced injury. Through a comprehensive pooled screen of miRNA function in Dgcr8-deficient organoids, we observe that the loss of the miR-200 family leads to the hyperactivation of the p53 pathway, thereby reducing ISCs and impairing epithelial regeneration. Notably, downregulation of the miR-200 family and hyperactivation of the p53 pathway are verified in colonic tissues from patients with active ulcerative colitis (UC). Most importantly, the transient supply of miR-200 through the oral delivery of lipid nanoparticles (LNPs) carrying miR-200 restores ISCs and promotes intestinal regeneration in mice following acute injury. Our study implies the miR-200/p53 pathway as a promising therapeutic target for active UC patients with diminished levels of the miR-200 family. Furthermore, our findings suggest that the clinical application of LNP-miRNAs could enhance the efficacy, safety, and acceptability of existing therapeutic modalities for intestinal diseases.


Subject(s)
Colitis, Ulcerative , MicroRNAs , Humans , Animals , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Tumor Suppressor Protein p53/metabolism , Regeneration , RNA-Binding Proteins , Intestines , Intestinal Mucosa , Colitis, Ulcerative/metabolism
3.
Front Cardiovasc Med ; 10: 1247434, 2023.
Article in English | MEDLINE | ID: mdl-37840954

ABSTRACT

Vascular diseases are the leading cause of morbidity and mortality worldwide and are urgently in need of diagnostic biomarkers and therapeutic strategies. Circular RNAs (circRNAs) represent a unique class of RNAs characterized by a circular loop configuration and have recently been identified to possess a wide variety of biological functions. CircRNAs exhibit exceptional stability, tissue specificity, and are detectable in body fluids, thus holding promise as potential biomarkers. Their encoding function and stable gene expression also position circRNAs as an excellent alternative to gene therapy. Here, we briefly review the biogenesis, degradation, and functions of circRNAs. We summarize circRNAs discovered in major vascular diseases such as atherosclerosis and aneurysms, with a particular focus on molecular mechanisms of circRNAs identified in vascular endothelial cells and smooth muscle cells, in the hope to reveal new directions for mechanism, prognosis and therapeutic targets of vascular diseases.

4.
Environ Sci Pollut Res Int ; 30(43): 97195-97208, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37589843

ABSTRACT

Lincomycin (LC) is an extensively applied broad-spectrum antibiotic, and its considerable residues in wastewater have caused a series of environmental problems, which makes degradation of LC wastewater extremely urgent. In this work, we have constructed a novel boron nitride (BN) and samarium (Sm) co-modified Ti/PbO2 as anode for high-performance degradation of LC wastewater. Compared with Ti/PbO2, Ti/PbO2-Sm, and Ti/PbO2-BN electrodes, Ti/PbO2-BN-Sm electrode with smaller pyramidal particles possesses higher oxygen evolution potential (2.32 V), excellent accelerated service life (103 h), and outstanding electrocatalytic activity. The single-factor experiments demonstrate that under optimized conditions (current density of 20 mA.cm-2, 6.0 g L-1 Na2SO4, pH 9, and temperature of 30°C), removal rate and COD degradation rate of LC at 3 h have reached 92.85% and 89.11%, respectively. At the same time, degradation of LC is in accordance with the primary kinetic model. Based on the analysis of high-performance liquid chromatography-mass spectrometry (HPLC-MS), four possible degradation pathways are hypothesized. Therefore, efficient electrochemical degradation of LC by using an extremely long-life Ti/PbO2 electrode with high catalytic activity may be a promising method.


Subject(s)
Lincomycin , Samarium , Wastewater , Electroplating , Titanium , Electrodes
5.
Front Oncol ; 13: 1110751, 2023.
Article in English | MEDLINE | ID: mdl-37020877

ABSTRACT

Purpose: This study aimed to explore the possibility of utilizing hepatitis B core protein (HBc) virus-like particles (VLPs) encapsulate doxorubicin (Dox) to reduce the adverse effect caused by its off-target and toxic side effect. Methods: Here, a triple-negative breast cancer (TNBC) tumor-targeting GE11-HBc VLP was constructed through genetic engineering. The GE11 peptide, a 12-amino-acid peptide targeting epidermal growth factor receptor (EGFR), was inserted into the surface protein loops of VLPs. The Dox was loaded into HBc VLPs by a thermal-triggered encapsulation strategy. The in vitro release, cytotoxicity, and cellular uptake of TNBC tumor-targeting GE11-HBc VLPs was then evaluated. Results: These VLPs possessed excellent stability, DOX loading efficiency, and preferentially released drug payload at high GSH levels. The insertion of GE11 targeting peptide caused improved cellular uptake and enhanced cell viability inhibitory in EGFR high-expressed TNBC cells. Conclusion: Together, these results highlight DOX-loaded, EGFR-targeted VLPs as a potentially useful therapeutic choice for EGFR-overexpressing TNBC.

6.
Biochem Biophys Res Commun ; 558: 107-113, 2021 06 18.
Article in English | MEDLINE | ID: mdl-33906109

ABSTRACT

MicroRNAs play an irreplaceable role in gene expression regulation. Upregulation of several miRNAs increases the risk of invasion and metastasis of breast cancer cells. An oncogenic miRNA, miR-21, is highly expressed in triple-negative breast cancer (TNBC) and is associated with tumor proliferation, invasion, carcinogenesis, prognosis, and therapeutic resistance. However, targeted delivery of therapeutic anti-miRNAs into cancer cells remains challenging, especially for TNBC. In this study, we report the application of an RNA nanotechnology-based platform for the targeted delivery of anti-miR-21 by epidermal growth factor receptor (EGFR) aptamer in vitro to TNBC and chemical-resistant breast cancer cells. RNA nanoparticles reduced cell viability and sensitized breast cancer cells to doxorubicin (DOX) treatment in vitro. Inhibition of miR-21 by RNA nanoparticles suppressed TNBC cell invasion, migration, and colony formation. The results indicate the potential application of nanotechnology-based delivery platforms in clinical anti-cancer therapeutics.


Subject(s)
Aptamers, Nucleotide/genetics , Aptamers, Nucleotide/therapeutic use , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/therapy , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Apoptosis/genetics , Aptamers, Nucleotide/administration & dosage , Cell Cycle/drug effects , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/genetics , Cell Survival/drug effects , Cell Survival/genetics , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Female , Gene Knockdown Techniques , Humans , Molecular Targeted Therapy/methods , Nanoparticles/administration & dosage , Nanoparticles/therapeutic use , Nanotechnology , Neoplasm Invasiveness/genetics , Triple Negative Breast Neoplasms/pathology , Tumor Stem Cell Assay
7.
Medicine (Baltimore) ; 100(4): e24441, 2021 Jan 29.
Article in English | MEDLINE | ID: mdl-33530248

ABSTRACT

ABSTRACT: To develop a useful score for predicting the prognosis of severe corona virus disease 2019 (COVID-19) patients.We retrospectively analyzed patients with severe COVID-19 who were admitted from February 10, 2020 to April 5, 2020. First, all patients were randomly assigned to a training cohort or a validation cohort. By univariate analysis of the training cohort, we developed combination scores and screened the superior score for predicting the prognosis. Subsequently, we identified the independent factors influencing prognosis. Finally, we demonstrated the predictive efficiency of the score in validation cohort.A total of 145 patients were enrolled. In the training cohort, nonsurvivors had higher levels of lactic dehydrogenase than survivors. Among the 7 combination scores that were developed, lactic dehydrogenase-lymphocyte ratio (LLR) had the highest area under the curve (AUC) value for predicting prognosis, and it was associated with the incidence of liver injury, renal injury, and higher disseminated intravascular coagulation (DIC) score on admission. Univariate logistic regression analysis revealed that C-reactive protein, DIC score ≥2 and LLR >345 were the factors associated with prognosis. Multivariate analysis showed that only LLR >345 was an independent risk factor for prognosis (odds ratio [OR] = 9.176, 95% confidence interval [CI]: 2.674-31.487, P < .001). Lastly, we confirmed that LLR was also an independent risk factor for prognosis in severe COVID-19 patients in the validation cohort where the AUC was 0.857 (95% CI: 0.718-0.997).LLR is an accurate predictive score for poor prognosis of severe COVID-19 patients.


Subject(s)
COVID-19/blood , L-Lactate Dehydrogenase/blood , Lymphocyte Count , Aged , COVID-19/mortality , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index
8.
Environ Sci Pollut Res Int ; 28(14): 17290-17305, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33394438

ABSTRACT

The efficient separation of low-concentration radionuclides by the eco-friendly adsorbent is a compelling requirement in the development of nuclear industry. Hence, a novel composite consisted of one-dimensional palygorskite (Pal) and three-dimensional pomelo peel (PP) is prepared by self-assembly approach (PP/Pal) and coupling agent approach (PP/KPal) for removing uranium (U(VI)) from aqueous solution. Moreover, the mass ratio (PP/Pal), adsorbent dosage, pH, contact time, temperature, and ionic strength are investigated. Two adsorption kinetic models and isotherm models are used to investigate the kinetic behaviors and adsorption capacity, respectively. The maximum adsorption capacities were 370.5 mg·g-1 on PP/Pal and 357.3 mg·g-1 on PP/KPal at pH 6.0, contact time 150 min and 25 °C. Meanwhile, the composite can be easily separated from water via a simple filtering. Furthermore, thermodynamic parameters indicate that adsorption is an endothermic and spontaneous process. And the surface complexation, ion exchange, and electrostatic attraction play a vital role. This work shows that the PP/Pal composite with high efficiency, low cost, and green has a further application in the treatment of wastewater containing U(VI).


Subject(s)
Magnesium Compounds , Silicon Compounds , Adsorption , Hydrogen-Ion Concentration , Kinetics , Water
9.
J Nanobiotechnology ; 19(1): 13, 2021 Jan 07.
Article in English | MEDLINE | ID: mdl-33413427

ABSTRACT

BACKGROUND: To date, triple-negative breast cancer (TNBC) treatment options are limited because of the loss of target receptors and, as a result, are only managed with chemotherapy. What is worse is that TNBC is frequently developing resistance to chemotherapy. By using small interfering RNA (siRNA)-based therapeutics, our recent work demonstrated X-box-binding protein 1 (XBP1) was linked to human epidermal growth factor receptor 2 positive (HER2+) breast cancer development and chemoresistance. Given the instability, off-target effects, net negative charge, and hydrophobicity of siRNA in vivo utilization and clinical transformation, its use in treatment is hampered. Thus, the development of a siRNA-based drug delivery system (DDS) with ultra-stability and specificity is necessary to address the predicament of siRNA delivery. RESULTS: Here, we assembled RNase resistant RNA nanoparticles (NPs) based on the 3WJ structure from Phi29 DNA packaging motor. To improved targeted therapy and sensitize TNBC to chemotherapy, the RNA NPs were equipped with an epidermal growth factor receptor (EGFR) targeting aptamer and XBP1 siRNA. We found our RNA NPs could deplete XBP1 expression and suppress tumor growth after intravenous administration. Meanwhile, RNA NPs treatment could promote sensitization to chemotherapy and impede angiogenesis in vivo. CONCLUSIONS: The results further demonstrate that our RNA NPs could serve as an effective and promising platform not only for siRNA delivery but also for chemotherapy-resistant TNBC therapy.


Subject(s)
Bacteriophages/genetics , Drug Delivery Systems/methods , RNA, Small Interfering/pharmacology , Triple Negative Breast Neoplasms/drug therapy , Animals , Apoptosis , Cell Cycle , Cell Line, Tumor , Cell Survival , ErbB Receptors/metabolism , Female , Gene Knockdown Techniques , Humans , Mice , Mice, Nude , X-Box Binding Protein 1/genetics , X-Box Binding Protein 1/metabolism , Xenograft Model Antitumor Assays
10.
Environ Sci Pollut Res Int ; 28(2): 1919-1932, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32862342

ABSTRACT

Removing Co(II) from wastewater is urgent due to the threat to the environment and human health. In the work, the nanocomposite of graphene oxide-modified palygorskite (mPal-GO) is synthesized by cross-linking one-dimensional palygorskite (Pal) with two-dimensional material graphene oxide (GO), and used to remove Co(II) from wastewater. Its structure is characterized by Fourier transformed infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Brunauer-Emmett-Teller (BET) surface area measurement. The parameters, such as mass ratio (GO:mPal), temperature, pH, and contact time, are carefully investigated. The results indicate that pseudo-second-order equation and Langmuir isotherm model are the best fitting one in the adsorption process of Co(II) onto mPal-GO. The maximum adsorption capacity achieves 16.9 mg/g at pH = 6.0 and T = 298 K according to the Langmuir model analysis. Furthermore, mPal-GO can be reused more than 5 times with a slight decrease according to the adsorption-desorption cycle experiments. Finally, mPal-GO with the low-cost and easy separation is a promising candidate for removing of Co(II) from wastewater.


Subject(s)
Graphite , Nanocomposites , Water Pollutants, Chemical , Adsorption , Humans , Kinetics , Magnesium Compounds , Silicon Compounds , Spectroscopy, Fourier Transform Infrared , Wastewater , Water Pollutants, Chemical/analysis
11.
ACS Appl Mater Interfaces ; 12(29): 32360-32371, 2020 Jul 22.
Article in English | MEDLINE | ID: mdl-32613835

ABSTRACT

siRNA therapeutics as an emerging class of drug development is successfully coming to clinical utilization. The RNA-based therapy is widely utilized to explore the mechanism and cure a variety of gene-specific diseases. Tumor is an oncogene-driven disease; many genes are related to tumor progression and chemoresistance. Although human epidermal growth factor receptor 2 (HER2)-targeted monoclonal antibody therapy has dramatically improved the survival rate, chemotherapy remains essential to HER2-positive (HER2+) breast cancer patients. Recently, X-box binding protein 1 (XBP1) has been involved in triple-negative breast cancer (TNBC) chemoresistance and progression, but its function in HER2+ breast cancer is poorly explored. Here, we silenced XBP1 expression using RNase-resistant RNA nanoparticles (NPs). Intravenous injection of RNA NPs with HER2-specific aptamers resulted in strong binding to tumors but not to healthy tissues. XBP1 deletion by RNA NPs impaired angiogenesis and inhibited cell proliferation, significantly suppressed breast cancer growth, and promoted the sensitization of chemotherapy in an HER2+ breast cancer mouse model. Overall, these results reveal the function of XBP1 in HER2+ breast cancer development and chemoresistance and imply that targeting XBP1 by RNA NPs may offer an easy and promising strategy for a combination treatment of breast cancer in the future.


Subject(s)
Aptamers, Nucleotide/chemistry , Nanoparticles/chemistry , RNA, Small Interfering/metabolism , Receptor, ErbB-2/metabolism , Triple Negative Breast Neoplasms/metabolism , X-Box Binding Protein 1/metabolism , Animals , Aptamers, Nucleotide/administration & dosage , Cell Proliferation , Female , Humans , Injections, Intravenous , Mammary Neoplasms, Experimental/metabolism , Mammary Neoplasms, Experimental/pathology , Mice , Nanoparticles/administration & dosage , Particle Size , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/chemistry , Surface Properties , Triple Negative Breast Neoplasms/pathology , X-Box Binding Protein 1/chemistry , X-Box Binding Protein 1/genetics
12.
Bioconjug Chem ; 31(8): 1917-1927, 2020 08 19.
Article in English | MEDLINE | ID: mdl-32639141

ABSTRACT

Utilizing nanoparticles to deliver subunit vaccine is considered to be a promising strategy to improve immune response. However, currently reported systems suffered from one or more points, for example, delicate design on molecular structures and elaborate synthesis process, low antigen and/or adjuvant encapsulation efficiency, involvement of toxic materials, and denaturing of bioactivity of antigen and/or adjuvant. To address these issues, here, for the first time, we developed a one-pot method to produce a subunit vaccine by using hexa-histidine metal assembly (HmA) to codeliver tumor-associated antigens (GP100, a peptide KTWGQYWQV) and adjuvant (CpG). The generation of subunit vaccines was detailedly characterized by various techniques, including dynamic scatter, scanning electron microscopy, transmission electron microscopy, UV-visible spectroscopy, agarose gel electrophoresis, etc. HmA displayed high efficiency on encapsulating both subunits (GP100 and CpG) under mild conditions, and the generated subunit vaccine showed a pH-dependent release profile of loaded subunits. In the cellular tests, these subunit vaccines behaved with a quick endocytosis into immune cells and a fast endo/lysosomes escape, inducing maturation of antigen presentative cells and stimulating a potent cellular immune response. These results suggested that HmA is a robust platform for fabricating subunit vaccine, with immense potential for the immunotherapy of various diseases.


Subject(s)
Metals/chemistry , Organometallic Compounds/chemistry , Vaccines/immunology , Animals , Cell Line , Cytokines/genetics , Cytokines/metabolism , Drug Delivery Systems , Gene Expression Regulation , Immunity, Cellular , Mice , Nanoparticles , Protein Subunits , Vaccines, Synthetic/immunology
13.
Mol Pharm ; 17(7): 2487-2498, 2020 07 06.
Article in English | MEDLINE | ID: mdl-32469222

ABSTRACT

Fully effective vaccines must induce both potent humoral and cellular immunities. Nanoparticles coencapsulating antigens and adjuvants have shown promising advantages as subunit vaccines in many aspects. However, the low loading efficiency and complicated synthesis process of these nanomaterials need to be improved. Here, we utilized hexahistidine (His6)-metal assembly (HmA) particles as carriers to codeliver ovalbumin peptides and cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs). We found that antigen/adjuvant-carrying HmA can efficiently enter into antigen-presenting cells and help the antigens escape from lysosomes to induce the maturation of these cells in vitro, characterized by increasing expression levels of costimulatory molecules and cytokines. More importantly, the vaccines with high biocompatibility can elicit strong humoral and cellular immunities by improving secretion of specific antibodies and cytokines, enhancing activation of DCs and T cells in vivo. Our results suggest that HmA provides a new approach for subunit vaccines by codelivery of antigens and adjuvants.


Subject(s)
Adjuvants, Immunologic/chemistry , Histidine/chemistry , Metal Nanoparticles/chemistry , Oligodeoxyribonucleotides/immunology , Oligopeptides/chemistry , Ovalbumin/immunology , Vaccines, Subunit/chemistry , Animals , Antibodies/immunology , Cell Survival/drug effects , Cytokines/metabolism , Dendritic Cells/drug effects , Dendritic Cells/immunology , Female , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Macrophages/drug effects , Macrophages/immunology , Metal Nanoparticles/toxicity , Metal Nanoparticles/ultrastructure , Mice , Mice, Inbred C57BL , Microscopy, Electron, Scanning , Oligodeoxyribonucleotides/administration & dosage , Ovalbumin/administration & dosage , RAW 264.7 Cells , T-Lymphocytes/drug effects , T-Lymphocytes/immunology
14.
ACS Appl Bio Mater ; 3(8): 5331-5341, 2020 Aug 17.
Article in English | MEDLINE | ID: mdl-35021707

ABSTRACT

Triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer, is difficult to be targeted therapeutically due to negative expression of the bioreceptor, which leads to the poorest overall four-year survival rate among all cancer subtypes. We proposed that the nanomedicine featuring high payload and pH-responsive release of the loaded drugs could assist the TNBC treatment. In the present study, the His6-metal assemblies (HmA) were employed to encapsulate the doxorubicin (Dox), and the effect of HmA loaded with Dox (HmA@Dox) on treating TNBC was evaluated in vitro and in vivo. We found that the participation of Dox in the formation of HmA leads to high loading efficiency (99.4% for concentration ≤ 1 mg/mL) and the loading capacity (50.7% for concentration ≥ 10 mg/mL) of Dox encapsulated into HmA. HmA@Dox exhibited a narrow size distribution on the nanoscale, a pH-responsive release of loaded Dox, a quick endocytosis process, and fast lysosome escape. Most importantly, the HmA@Dox showed high efficacy in killing various breast cancer cells (MCF-7, MDA-MB-231, and MDA-MB-453) in vitro and depressing the development of TNBC in vivo. Our results demonstrated that such a strategy for designing a nanomedicine with high payload and responsive release of drugs to the environment around the tumor was of great importance to treat TNBC.

15.
ACS Appl Mater Interfaces ; 11(42): 39209-39218, 2019 Oct 23.
Article in English | MEDLINE | ID: mdl-31553877

ABSTRACT

Proteins are considered to be one of the most important highly reproducible and monodisperse building blocks with specific functions in life sciences and material science. Protein capsules and their hybrids composed of protein-polymer conjugates have been intensively explored in drug delivery, catalysis, and cell-mimicking functions. Herein, we present a facile, universal, and efficient method to fabricate the diverse protein capsules, independent of the molecular weight (Mw), isoelectric points (IEP), wettability, amino acid sequence, and functional domains of enumerated proteins. The protein capsules were well characterized by various techniques. Furthermore, their ability to store the original protein functionality was demonstrated, which was mainly embodied in their enzyme responsiveness and good biocompatibility in vitro and in vivo. We believe that these protein capsules have multiple potential applications such as in drug delivery, tissue engineering, catalysis, and other application fields.

16.
Mol Pharm ; 16(7): 2902-2911, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31184906

ABSTRACT

The physical properties of nanoparticles (NPs), such as size, surface chemistry, elasticity, and shape, have exerted a profound influence on tumor penetration. However, the effect of shape on cellular uptake and tumor penetration is still unclear because of the different chemical compositions and shapes of tested particles and the use of inapposite cellular models. To discover the effect of NP shapes on cellular uptake and tumor penetration and bridge the gap between models in vivo and in vitro, elongated polystyrene (PS) NPs with a fixed volume, an identical chemical composition, and the same zeta potential, but with different aspect ratios (ARs), were generated. The physical properties, cellular uptake, tumor penetration, and corresponding mechanisms of these NPs were thoroughly investigated. We discovered that the elongated PS particles with higher ARs had lower uptake rates in the 2-dimensional cell monolayer culture model in vitro, but they showed optimal ARs in the evaluated three-dimensional spheroid model. Although the elongated PS particles had a similar tumor penetration mechanism (mainly through extracellular pathways), the percentage of penetration using these mechanisms was strongly dependent on the ARs. As an alternative model for studies in vivo, spheroids were used instead of the cell monolayer for the development of drug delivery systems. In addition, the physicochemical properties of NPs must be delicately balanced and adjusted to achieve the best therapeutic outcomes.


Subject(s)
Drug Delivery Systems/methods , Nanoparticles/chemistry , Polypropylenes/chemistry , Spheroids, Cellular/drug effects , Uterine Cervical Neoplasms/metabolism , Cell Membrane Permeability/drug effects , Cell Survival/drug effects , Extracellular Fluid/drug effects , Extracellular Matrix/drug effects , Female , HeLa Cells , Humans , Polystyrenes/chemistry , Tumor Microenvironment/drug effects
17.
Colloids Surf B Biointerfaces ; 181: 549-560, 2019 Sep 01.
Article in English | MEDLINE | ID: mdl-31185447

ABSTRACT

Bone related implants have huge potential market in global. Improving the implant outcomes and probability of implant success are highly pursued to relieve the pain of patients and burden on native healthy system. There are growing evidence to support reactive oxygen species (ROS) directly involved in bone diseases and failure of implants. Taking advantage of the antioxidant property of tannic acid (TA) and biocompatibility of gelatin (Gel), the TA/Gel multilayer film was fabricated by layer by layer method, and the growing process of this film was monitored by QCM-D. The physical properties of TA/Gel film were further well characterized and modulated. In cellular test, TA/Gel multilayer film displayed good antioxidant properties under ROS stress environment (after H2O2 treatment flourscence intensity increased 38.9-fold for glasses, only ˜6-fold for (TA/Gel)8), facilitating cell attachment, fastening spreading at early stage and accelerating proliferation in beginning 2 day. Area per cell on (TA/ Gel)4-0.15 M is 1.5-fold higher than that on glass at 2 h, while it became 2.3-fold higher at 4 h. Moreover, these films performed both enhanced osteogenesis in vitro test and bone formation in vivo in the animal bone implanting model. Our results supported discovered the antioxidant coating played the critical role one the success of bone related implants, which could be particularly noted in the future implant design. And the strategy applied here, utilizing the interactions between polyphenol and proteins to construct multilayer film, will pave the way to fabricating an antioxidant coating.


Subject(s)
Antioxidants/chemistry , Gelatin/chemistry , Polyphenols/chemistry , 3T3 Cells , Animals , Cells, Cultured , Mice , Particle Size , Surface Properties
18.
Acta Biomater ; 90: 441-452, 2019 05.
Article in English | MEDLINE | ID: mdl-30953803

ABSTRACT

It is of considerable interest to construct an ideal drug delivery system (i.e., high drug payload, minimal cytotoxicity, rapid endocytosis, and lysosomal escape) under mild conditions for disease treatment, tissue engineering, bioimaging, etc. Inspired by the coordinative interactions between histidine and metal ions, we present the facile synthesis of hexahistidine (His6)-metal assembly (HmA) particles under mild conditions for the first time. The HmA particles presented a high loading capacity, a wide variety of loadable drugs, minimal cytotoxicity, quick internalization, the ability to bypass the lysosomes, and rapid intracellular drug release. In addition, HmA encapsulation largely improved the antitumor ability of camptothecin (CPT) relative to free CPT. By capitalizing on these promising features in drug delivery, HmA will have great potential in various biomedical fields. STATEMENT OF SIGNIFICANCE: It is of considerable interest to construct an ideal drug delivery system (i.e., high drug payload, minimal cytotoxicity, rapid endocytosis, and lysosomal escape) under mild conditions. Inspired by the coordinative interactions between histidine and metal ions, we present for the first time the facile synthesis of Hexahistidine (His6)-metal assembly (HmA) particles under mild conditions. The HmA particles exhibited a high loading capacity, a wide variety of loadable drugs, minimal cytotoxicity, quick internalization, the ability to bypass the lysosomes, and rapid intracellular drug release. By capitalizing on these promising features in drug delivery, HmA will have great potential in various biomedical fields.


Subject(s)
Antineoplastic Agents , Camptothecin , Coordination Complexes , Histidine , Lysosomes/metabolism , Neoplasms , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Camptothecin/chemistry , Camptothecin/pharmacokinetics , Camptothecin/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/pharmacokinetics , Coordination Complexes/pharmacology , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/pharmacology , HeLa Cells , Histidine/chemistry , Histidine/pharmacokinetics , Histidine/pharmacology , Humans , Lysosomes/pathology , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology
19.
Chemosphere ; 224: 707-715, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30851522

ABSTRACT

In this work, dimensionally stable Ti/SnO2-RuO2 electrode is successfully prepared using thermal decomposition method for the electrocatalytic degradation of high-concentration industrial gallic acid (GA) effluent in detail. The surface morphology, crystal structure and element analysis of as-prepared Ti/SnO2-RuO2 electrode are characterized by scanning electron microscopy, X-ray diffraction and X-ray fluorescence spectrometer, respectively. In addition, cyclic voltammetry, polarization curve and accelerated life tests are exploited to investigate the electrocatalytic activity and stability of Ti/SnO2-RuO2 electrode. Orthogonal experiment shows that, among the factors (current density, temperature and initial pH), current density is pivotal parameter influencing the degradation efficiency of industrial GA effluent. COD removal and degradation efficiencies of GA effluent reach up to 76.9% and 80.1% after 6 h, respectively, at the optimal conditions (current density of 10 mA cm-2, pH 6 and 35 °C). The degradation of GA effluent follows pseudo-first-order reaction kinetics. This work provides an in-depth theoretical support and application of electrocatalytic technology to the treatment of high-concentration industrial GA effluent.


Subject(s)
Biological Oxygen Demand Analysis/methods , Gallic Acid/chemistry , Ruthenium Compounds/chemistry , Tin Compounds/chemistry , Titanium/chemistry , Water Pollutants, Chemical/chemistry , Water Purification/methods , Electrodes , X-Ray Diffraction
20.
Colloids Surf B Biointerfaces ; 177: 178-187, 2019 May 01.
Article in English | MEDLINE | ID: mdl-30738324

ABSTRACT

Constructing intracellular degradable drug delivery vehicles is critical to fully exert the function of loaded drugs. Considering the poly (amino acid) is sensitively degradable to acid and enzyme which indwell in the mature lysosome, we here presented the poly(amino acid) capsules constructed by the synthetic poly(amino acid), (poly-glutamic acid, PGA and poly-ornithine, POR). The fabrication of Dox loaded poly (amino acid) capsules was demonstrated, and was thoroughly characterized by various techniques, including Zetasizer, SEM, TEM, fluorescent microscopy, and confocal laser scan microscopy. By controlling fabrication process, we tuned the carriers with different physical properties (charges and stiffness). Then, we thoroughly investigated the effects of these properties on the intracellular uptake and anti-cancer abilities of various carriers@Dox. In addition, the degradability of poly(amino acid) capsules was studied to reveal the release profiles of the carriers with or without templates from the side aspect. We found the positively charged and stiffer carriers mainly contributed to the cellular uptake process and amount, while both the uptake amount and degradability of the endocytosed carriers@Dox played a critical role on the cytotoxicity. We believe the findings here could pave the way for designing poly(amino acid) capsules or other degradable polymers based on poly(amino acid) as the drug delivery vehicles.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Doxorubicin/pharmacology , Drug Delivery Systems , Peptides/chemistry , Polyglutamic Acid/chemistry , Antibiotics, Antineoplastic/chemistry , Capsules/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Doxorubicin/chemistry , Drug Carriers/chemistry , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Molecular Structure , Particle Size , Surface Properties , Tumor Cells, Cultured
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