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1.
J Mater Chem B ; 12(20): 4759-4784, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38682294

RESUMO

The liver, a complex and vital organ in the human body, is susceptible to various diseases, including metabolic disorders, acute hepatitis, cirrhosis, and hepatocellular carcinoma. In recent decades, these diseases have significantly contributed to global morbidity and mortality. Currently, liver transplantation remains the most effective treatment for hepatic disorders. Nucleic acid therapeutics offer a selective approach to disease treatment through diverse mechanisms, enabling the regulation of relevant genes and providing a novel therapeutic avenue for hepatic disorders. It is expected that nucleic acid drugs will emerge as the third generation of pharmaceuticals, succeeding small molecule drugs and antibody drugs. Lipid nanoparticles (LNPs) represent a crucial technology in the field of drug delivery and constitute a significant advancement in gene therapies. Nucleic acids encapsulated in LNPs are shielded from the degradation of enzymes and effectively delivered to cells, where they are released and regulate specific genes. This paper provides a comprehensive review of the structure, composition, and applications of LNPs in the treatment of hepatic disorders and offers insights into prospects and challenges in the future development of LNPs.


Assuntos
Portadores de Fármacos , Lipídeos , Hepatopatias , Nanopartículas , Humanos , Nanopartículas/química , Portadores de Fármacos/química , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Hepatopatias/terapia , Lipídeos/química , Animais , Sistemas de Liberação de Medicamentos
2.
Food Chem ; 444: 138634, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38330608

RESUMO

Quercetin, an essential flavonoid compound, exhibits diverse biological activities including anti-inflammatory and antioxidant effects. Nevertheless, due to its inadequate solubility in water and vulnerability to degradation, pure quercetin is constrainedly utilized in pharmaceutical formulations and functional foods. Considering the existing scarcity of nanoparticles consisted of zein and hydrophobic biopolymers, this study developed a quercetin-loaded nanoencapsulation based on zein, shellac, and chitosan (QZSC). When the mass ratio of zein to chitosan was 4:1, the encapsulation efficiency of QZSC reached 74.95%. The ability of QZSC for scavenging DPPH radicals and ABTS radicals increased from 59.2% to 75.4% and from 47.0% to 70.2%, respectively, compared to Quercetin. For QZSC, the maximum release amount of quercetin reached 59.62% in simulated gastric fluid and 81.64% in simulated intestinal fluid, achieving controlled and regulated release in vitro. In summary, this study offers a highly promising encapsulation strategy for hydrophobic bioactive substances that are prone to instability.


Assuntos
Quitosana , Nanopartículas , Resinas Vegetais , Zeína , Quercetina/química , Zeína/química , Quitosana/química , Preparações de Ação Retardada/química , Nanopartículas/química , Tamanho da Partícula
3.
Sci Total Environ ; 915: 170125, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38242469

RESUMO

Bacterial infections pose a seriously threat to the safety of the environment and human health. In particular, the emergence of drug-resistant pathogens as a result of antibiotic abuse and high trauma risk has rendered conventional therapeutic techniques insufficient for treating infections by these so-called "superbugs". Therefore, there is an urgent need to develop highly efficient and environmentally-friendly antimicrobial agents. Bismuth-based nanomaterials with unique structures and physicochemical characteristics have attracted considerable attention as promising antimicrobial candidates, with many demonstratingoutstanding antibacterial effects upon being triggered by broad-spectrum light. These nanomaterials have also exhibited satisfactory energy band gaps and electronic density distribution with improved photonic properties for extensive and comprehensive applications after being modified through various engineering methods. This review summarizes the latest research progress made on bismuth-based nanomaterials with different morphologies, structures and compositions as well as the different methods used for their synthesis to meet their rapidly increasing demand, especially for antibacterial applications. Moreover, the future prospects and challenges regarding the application of these nanomaterials are discussed. The aim of this review is to stimulate interest in the development and experimental transformation of novel bismuth-based nanomaterials to expand the arsenal of effective antimicrobials.


Assuntos
Anti-Infecciosos , Infecções Bacterianas , Nanocompostos , Humanos , Bismuto/química , Antibacterianos/química
4.
ACS Nano ; 18(5): 4140-4158, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38134247

RESUMO

Ischemic stroke is one of the major causes of death and disability worldwide, and an effective and timely treatment of ischemic stroke has been a challenge because of the narrow therapeutic window and the poor affinity with thrombus of the thrombolytic agent. In this study, rPZDCu, a multifunctional nanoparticle (NP) with the effects of thrombolysis, reactive oxygen species (ROS) scavenging, and neuroprotection, was synthesized based on an ultrasmall Cu4.6O NP, the thrombolytic agent rt-PA, and docosahexaenoic acid (DHA), which is a major component of the neuronal membrane. rPZDCu showed strong thrombus-targeting ability, which was achieved by the platelet cell membrane coating on the NP surface, and a good thrombolytic effect in both the common carotid artery clot model and embolic middle cerebral artery occlusion (MCAO) model of rats. Furthermore, rPZDCu exhibited a good escape from the phagocytosis of macrophages, effective promotion of the polarization of microglia, and efficient recovery of neurobiological and behavioral functions in the embolic MCAO model of rats. This is a heuristic report of (1) the Cu0/Cu+ NP for the treatments of brain diseases, (2) the integration of DHA and ROS scavengers for central nervous system therapies, and (3) diselenide-based ROS-responsive NPs for ischemic stroke treatments. This study also offers an example of cell membrane-camouflaged stimuli-responsive nanomedicine for brain-targeting drug delivery.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Nanopartículas , Acidente Vascular Cerebral , Trombose , Ratos , Animais , Fibrinolíticos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Trombose/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico
5.
Adv Mater ; 36(11): e2307695, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38150667

RESUMO

Treatment of diabetic wounds is a significant clinical challenge due to the massive infections caused by bacteria. In this study, multifunctional glycol chitosan and polydopamine-coated BiO1-x I (GPBO) nanoparticles (NPs) with near-infrared (NIR) photothermal and photocatalytic abilities are prepared. When infection occurs, the local microenvironment becomes acidic, and the pH-switchable GPBO can target the bacteria of the wound site. The NIR-assisted GPBO treatment exhibits anti-bacterial effects with fast response, high efficiency, and long duration to Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. GPBO achieves excellent photothermal imaging and CT imaging of the mouse subcutaneous abscess model. With the assistance of NIR irradiation, the GPBO promotes the healing of the diabetic wound model with the effects of anti-bacteria, anti-inflammation, the M2 polarization promotion of macrophages, and angiogenesis. This is the first-time report of nano-sized BiO1-x I. The synthesis and selected application for the imaging and targeted therapy of diabetic wounds are presented. This study offers an example of the NP-assisted precise diagnosis and therapy of bacterial infection diseases.


Assuntos
Quitosana , Diabetes Mellitus , Indóis , Nanopartículas , Polímeros , Camundongos , Animais , Bismuto , Oxigênio/farmacologia , Nanopartículas/uso terapêutico , Bactérias , Escherichia coli
6.
ACS Nano ; 17(5): 4414-4432, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36688425

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease characterized by the death of dopaminergic (DA) neurons and currently cannot be cured. One selected antisense oligonucleotide (ASO) is reported to be effective for the treatment of PD. However, ASO is usually intrathecally administered by lumbar puncture into the cerebral spinal fluid, through which the risks of highly invasive neurosurgery are the major concerns. In this study, ZAAM, an ASO-loaded, aptamer Apt 19S-conjugated, neural stem cell membrane (NSCM)-coated nanoparticle (NP), was developed for the targeted treatment of PD. NSCM facilitated the blood-brain barrier (BBB) penetration of NPs, and both NSCM and Apt 19S promoted the recruitment of the neural stem cells (NSCs) toward the PD site for DA neuron regeneration. The behavioral tests demonstrated that ZAAM highly improved the efficacy of ASO on PD by the targeted delivery of ASO and the recruitment of NSCs. This work is a heuristic report of (1) nonchemoattractant induced endogenous NSC recruitment, (2) NSCM-coated nanoparticles for the treatment of neurodegenerative diseases, and (3) systemic delivery of ASO for the treatment of PD. These findings provide insights into the development of biomimetic BBB penetrable drug carriers for precise diagnosis and therapy of central nervous system diseases.


Assuntos
Nanopartículas , Células-Tronco Neurais , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Barreira Hematoencefálica/metabolismo , Oligonucleotídeos Antissenso , Doenças Neurodegenerativas/metabolismo , Células-Tronco Neurais/metabolismo , Oligonucleotídeos , Neurônios Dopaminérgicos/metabolismo
7.
J Food Sci Technol ; 60(1): 92-102, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36618050

RESUMO

Riboflavin (RF) is one kind of vitamin B, which has low bioavailability due to the low water solubility and the high photosensitivity during food processing and storage. The anti-solvent precipitation method was applied to fabricate a zein-sodium alginate (SA) binary complexes delivery system with the loading of RF, which was aimed to enhance the delivery efficiency, stability, and controlled release of RF in the gastrointestinal (GI) tract. The formation mechanism, physicochemical properties as well as the digestion behaviors were investigated. The incorporation of SA significantly increased the diameter and decreased the surface positive charge of the nanoparticles. The surface morphology of the nanoparticles was characterized using the scanning electron microscope. The FTIR analysis revealed that the electrostatic attraction was the dominant binding force in the formation of the zein-SA binary complexes nanoparticles. In addition, the study on the in vitro release process showed that the zein-SA nanoparticles could delay the release of the RF under the simulated GI tract conditions, which improved their oral bioavailability. In summary, the zein-SA nanoparticle is an effective vehicle for the oral delivery of RF as well as other vitamins and bioactives in the applications of food and nutrition.

8.
Food Chem ; 404(Pt B): 134754, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36332578

RESUMO

Intelligent packaging not only protects food from environmental hazards but intuitively monitors the changes of food quality and safety. A novel intelligent packaging film with pH sensitivity and antibacterial and antioxidant effects was developed based on the highly cross-linked zein. The composite film with 0.05 g/g crosslinking agent had the best mechanical properties. The tensile strength (TS) and elongation-at-break (EBA) were 2.42 and 1.53 times of that of zein film, respectively. Moreover, the intelligent packaging showed longstanding antimicrobial and antioxidant effects because of the addition of the tea tree essential oil (TTEO)-loaded mesoporous silica nanoparticles (MSNs). The blueberry anthocyanin as colorimetric indicator was added in the packaging film to monitor the safety of meat products using a mobile phone. The color of the composite film as the packaging of the pork products changed from colorless to brown after 9-day storage to show the spoilage of the pork. To the best of our knowledge, this is the first-time report of 1) the application of TTEO-loaded MSNs for food packing, 2) the addition of TTEO as the antimicrobial agent for zein film, and 3) using the applications of mobile phone to measure the RBG value of the zein-based film. This study offers an example of the highly promising biodegradable intelligent packaging with multi-functions for the enhancement of food safety.


Assuntos
Carne de Porco , Carne Vermelha , Zeína , Animais , Suínos , Zeína/química , Carne Vermelha/análise , Antioxidantes , Embalagem de Alimentos , Antocianinas/química , Antibacterianos/farmacologia , Antibacterianos/química , Concentração de Íons de Hidrogênio
9.
Int J Mol Sci ; 23(10)2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35628131

RESUMO

For developing an effective interventional approach and treatment modality for PM2.5, the effects of omega-3 fatty acids on alleviating inflammation and attenuating lung injury induced by inhalation exposure of PM2.5 were assessed in murine models. We found that daily oral administration of the active components of omega-3 fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) effectively alleviated lung parenchymal lesions, restored normal inflammatory cytokine levels and oxidative stress levels in treating mice exposed to PM2.5 (20 mg/kg) every 3 days for 5 times over a 14-day period. Especially, CT images and the pathological analysis suggested protective effects of DHA and EPA on lung injury. The key molecular mechanism is that DHA and EPA can inhibit the entry and deposition of PM2.5, and block the PM2.5-mediated cytotoxicity, oxidative stress, and inflammation.


Assuntos
Ácidos Graxos Ômega-3 , Lesão Pulmonar , Administração Oral , Animais , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/uso terapêutico , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Inflamação/tratamento farmacológico , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Camundongos , Material Particulado/toxicidade
10.
Sci Adv ; 8(10): eabm7077, 2022 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-35263137

RESUMO

Glioma is the most common malignant primary brain tumor, and the accurate diagnosis of glioma has always been a challenge. Moreover, cerebellar glioma, which is difficult to be detected by magnetic resonance imaging, is not usually diagnosed until after the appearance of clinical symptoms. In this study, TRZD, a near-infrared (NIR) persistent luminescence (PL) nanoparticle with a dual function of imaging and therapy, was synthesized based on ZnGa2O4:Cr3+,Sn4+. TRZD showed excellent rechargeable NIR PL for more than 30 hours in vivo with good tissue penetration for long-term autofluorescence-free imaging. The tumor growth of both the subcutaneous and orthotropic glioma models was significantly inhibited by TRZD. This is the first-time approach using NIR PL nanoprobes for both diagnosis and therapy of glioma. This is also the first-time report of nanotechnology-based diagnosis and therapy of cerebellar gliomas. This study offers a highly promising multifunctional nanoparticle for theranostics of a wide range of brain diseases.


Assuntos
Glioma , Nanopartículas , Biomimética , Glioma/diagnóstico por imagem , Glioma/terapia , Humanos , Luminescência , Nanopartículas/uso terapêutico , Imagem Óptica/métodos
11.
J Nanosci Nanotechnol ; 21(12): 6041-6047, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34229802

RESUMO

Nano-particulate matters (NPM) induced the lung injury in mice were evaluated using quantitative micro-computed tomography in the present article. It is an important negative effect of health problems that NPM exposure provokes changes in the lung injury. The micro-computed tomography (CT) to assess lung injury in mouse models has been investigated. The dynamic structural changes in a NPM-induced lung injury mouse mode were monitored. Adults female BALB/C mice were repeatedly exposed to NPM, and micro-CT scans were performed at day 0, 3, 5 and 9. Lung samples were also collected for histological analysis at each time point. The total lung volume, the injured lung volume, and the normal lung volume were defined and calculated volume during the phase of NPM-exposure on the mice. The total and injured lung volumes of NPM-exposed mice were significantly larger than those of the mice at day 5 and 9. The data from micro-CT was consistent with alveolar enlargement and destruction by histological quantification from pathological section. The study for NPM-induced lung injury model by micro-CT may extend our understanding of the distinct pathophysiology of NPM induced lung injury in mice.


Assuntos
Lesão Pulmonar , Material Particulado , Animais , Modelos Animais de Doenças , Feminino , Pulmão/diagnóstico por imagem , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/diagnóstico por imagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Material Particulado/toxicidade , Microtomografia por Raio-X
12.
J Nanosci Nanotechnol ; 21(10): 5352-5362, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33875129

RESUMO

Fullerenol nanoparticles were found to significantly modulate the gut microbiota and selectively enrich the short-chain fatty acids (SCFAs) production by adjusting the gut microbacteria in mice models. In this research, we screened the C. butyricum from seven strains and investigated the interactions and mechanism between the C. butyricum and fullerenol NPs in vitro fermentation. The results shows that fullerenol NPs increased the amounts of acetate and butyrate of C. butyricum without significant bacteria growth in the complete medium. The activities of the butyryl-CoA: acetate CoA transferase (BUT), which are the main pathway to produce butyrate, were reduced while the activities of the butyrate kinase (BUK) were enhanced simultaneously. Surprisingly, fullerenol NPs promoted the growth of C. butyricum and L. lactis in low glucose medium, but they could not be direct carbon source in the culture. Moreover, when cocultured with C. butyricum and the bifidobacterial strains in fullerenols, the biomass and acetate production of C. butyricum were markedly increased while butyrate was decreased significantly.


Assuntos
Ácidos Graxos Voláteis , Microbacterium , Animais , Butiratos , Fermentação , Fulerenos , Camundongos
13.
Artigo em Inglês | MEDLINE | ID: mdl-32486636

RESUMO

Helicobacter pylori (H. pylori) eradication by antibiotics and proton pump inhibitor treatment is limited by the low pH microenvironment in the stomach and can lead to antibiotic resistance. We fabricated fullerenol nanoparticles (FNPs) with varied chemical structures responding to a pinacol rearrangement of vicinal hydroxyl to form carbonyls in low pH environments. An obvious increase in C═O/C-O was induced in low pH and was positively correlated with a peroxidase-like activity. The FNPs exerted an excellent effect on H. pylori eradication in vitro and in vivo because of their peroxidase-like activity. FNP treatment of a H. pylori biofilm revealed that FNPs broke down polysaccharides in cell wall components, resulting in collapse of the bacteria. The cycles of FNPs combining and dissociating with the peroxidase substrate were detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and confirmed that FNPs enhance peroxidase-like activity. Further, the isothermal titration calorimetry results showed that FNPs with more C═O/C-O had greater affinity to bind the peroxidase substrates. Therefore, we suggest that varied C═O/C-O serves as a switch to respond to low pH in the stomach to kill H. pylori by inducing a peroxidase-like activity. FNPs can also overcome the challenge of antibiotic resistance to achieve H. pylori eradication in the stomach.

14.
Nanoscale ; 12(22): 12174-12176, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32478778

RESUMO

Correction for 'Modulated podosome patterning in osteoclasts by fullerenol nanoparticles disturbs the bone resorption for osteoporosis treatment' by Kui Chen et al., Nanoscale, 2020, 12, 9359-9365, DOI: 10.1039/D0NR01625J.

15.
Nanoscale ; 12(17): 9359-9365, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32315013

RESUMO

Overactivation and excessive differentiation of osteoclasts (OCs) has been implicated in the course of bone metabolism-related diseases. Although fullerenol nanoparticles (fNPs) have been suggested to inhibit OC differentiation and OC function in our previous work, systemic studies on the effect of fNPs on bone diseases, e.g., osteoporosis (OP), in vivo remain elusive. Herein, it is demonstrated that fNPs significantly suppress the differentiation of OCs that derived from the murine bone marrow monocytes and inhibit the formation of the sealing zone by blocking the formation and patterning of podosomes in OCs spatiotemporally. In vivo, fNPs are supposed to be an efficient inhibitor of the overactivation of OCs in a LPS-induced bone erosion mouse model. The therapeutic effect of fNPs on osteoporosis is also investigated in an ovariectomy-induced osteoporosis rat model. The well-organized trabecular bone, the reduction in the number of TRAP positive cells, the improvement of bone-associated parameters, and the mechanical properties all demonstrate that fNPs, similar to diphosphonates, can be a promising candidate for the effective treatment of osteoporosis.


Assuntos
Reabsorção Óssea/prevenção & controle , Fulerenos/uso terapêutico , Nanopartículas/uso terapêutico , Osteoclastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Podossomos/efeitos dos fármacos , Animais , Osso Esponjoso/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Fêmur/efeitos dos fármacos , Fulerenos/química , Fulerenos/farmacologia , Camundongos , Proteínas dos Microfilamentos/metabolismo , Nanopartículas/química , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteogênese/efeitos dos fármacos , Osteoporose/patologia , Osteoporose/fisiopatologia , Podossomos/metabolismo , Podossomos/patologia , Ratos , Fosfatase Ácida Resistente a Tartarato/metabolismo
16.
ACS Appl Mater Interfaces ; 12(13): 14958-14970, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32142246

RESUMO

We report the construction of blood cell membrane cloaked mesoporous silica nanoparticles for delivery of nanoparticles [fullerenols (Fols)] with fibrinolysis activity which endows the active Fol with successful thrombolysis effect in vivo. In vitro, Fols present excellent fibrinolysis activity, and the Fol with the best fibrinolysis activity is screened based on the correlation between Fols' structure and their fibrinolysis activity. However, the thrombolytic effect in vivo is not satisfactory. To rectify the unsatisfactory situation and avoid the exogenous stimuli, a natural blood cell membrane cloaking strategy with loading the active Fol is chosen to explore as a novel thrombolysis drug. After cloaking, the therapeutic platform prolongs blood circulation time and enhances the targeting effect. Interestingly, compared with platelet membrane cloaking, red blood cell (RBC) membrane cloaking demonstrates stronger affinity with fibrin and more enrichment at the thrombus site. The Fol with RBC cloaking shows quick and efficient thrombolysis efficacy in vivo with less bleeding risk, more excellent blood compatibility, and better biosafety when compared with the clinical drug urokinase (UK). These findings not only validate the blood cell membrane cloaking strategy as an effective platform for Fol delivery on thrombolysis treatment, but also hold a great promising solution for other active nanoparticle deliveries in vivo.


Assuntos
Portadores de Fármacos/química , Membrana Eritrocítica/metabolismo , Fulerenos/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Membrana Eritrocítica/efeitos dos fármacos , Fibrinólise/efeitos dos fármacos , Fluoresceína/química , Fulerenos/metabolismo , Fulerenos/farmacologia , Fulerenos/uso terapêutico , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Nanopartículas/química , Ratos , Dióxido de Silício/química , Trombose/induzido quimicamente , Trombose/tratamento farmacológico , Trombose/patologia , Distribuição Tecidual , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
17.
Molecules ; 25(4)2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32092877

RESUMO

The intestinal epithelium is a major barrier that limits the absorption of oral drugs. The integrity of the epithelial tissue is a very important factor for preventing intestinal diseases. However, destabilization of the epithelium can promote the transportation of nanocarriers and increase the absorption of oral drugs. In our research, three different gold nanoparticles (GNPs) of the same size but with differing negative surface charge were designed and constructed as a model to determine the surface properties crucial for promoting absorptivity and bioavailability of the nanocarriers. The higher the ratio of surface carboxyl groups on GNPs, the higher capacity to induce transepithelial electrical resistance change and cell monolayer tight junction opening with higher permeability. The half carboxyl and half methyl surfaced GNPs displayed unique zonal surface patterns exhibited the greater ability to pass through intestinal epithelial cell layer but had a relatively small influence on tight junction distribution.


Assuntos
Portadores de Fármacos , Enterócitos/metabolismo , Ouro , Nanopartículas Metálicas/química , Células CACO-2 , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Enterócitos/citologia , Ouro/química , Ouro/farmacocinética , Ouro/farmacologia , Humanos , Permeabilidade
18.
Nanoscale ; 12(6): 3871-3878, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-31996882

RESUMO

Hyperactive osteoclasts (OCs) are a fundamental reason for excessive bone resorption and consequent osteoporosis that lead to one-third of the patients sustaining a fracture. OCs, with the help of acidifying vesicles containing vacuolar-type H+-ATPase (V-ATPase), transport cytoplasmic protons into a resorptive pit and create an acidic microenvironment where proteolytic enzymes degrade the bone matrix. Here, we report a previously undescribed application of gold nanoparticles (AuNPs) to inhibit excessive bone resorption by regulating the acidic microenvironment in which OCs resorb bone. Internalized AuNPs, with relatively abundant carboxyl groups, eventually accumulate in the membrane of the intracellular vesicles and interact with the V0 domain of V-ATPase, which prevents it from recruiting the V1 domain. This destroys the acid-secretion function of OCs. The therapeutic effect of AuNPs on bone resorption was assessed in an established lipopolysaccharide-induced bone erosion mouse model. Micro-computed tomography, histology, and tartrate-resistant acid phosphatase staining showed that AuNPs significantly reduced bone erosion. In summary, AuNPs are promising nano-functional materials for repairing bone defects by regulating OC acid secretion.


Assuntos
Reabsorção Óssea/metabolismo , Microambiente Celular/efeitos dos fármacos , Ouro/farmacologia , Nanopartículas Metálicas/química , Osteoclastos/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Ouro/química , Ouro/toxicidade , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Osteoclastos/metabolismo , Células RAW 264.7
19.
RSC Adv ; 10(60): 36378-36385, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35517946

RESUMO

The effects of dangling bonds on the magnetic properties of graphene oxide (GO) were studied experimentally by creating nanoholes on GO nanosheets. GO with more nanoholes (MHGO) and less nanoholes (LHGO) on graphene oxide nanosheets were synthesized. Results showed that nanoholes brought new dangling bonds for GO and the increase of the dangling bonds on GO could be adjusted by the amounts of the nanoholes on GO. The magnetism of GO was enhanced with increased density of nanoholes on GO (MHGO > LHGO > GO). Furthermore, the increased dangling bonds induced magnetic coupling between the spin units and so converted paramagnetism GO to ferromagnetism (MHGO, LHGO). The easy generation and adjustment of GO dangling bonds by nanoholes on GO nanosheets will promote the applications of GO.

20.
ACS Appl Bio Mater ; 2(10): 4612-4621, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-35021420

RESUMO

Nanocrystallization can improve the dissolvability of insoluble medicines in water, making them easier to administer. In the present study, sirolimus (SRL) was nanocrystallized, and the transport mechanism and efficacy of both formulations were compared in vitro and in vivo. The results showed that the 120 nm sirolimus nanocrystals (SRL NCs) had better ability to pass through the Caco-2 cell monolayer. SRL NCs were uptaken by Caco-2 cells via multiple endocytosis pathways, and the endoplasmic reticulum (ER), Golgi apparatus, and microtubules were identified as vital organelles for expelling SRL NCs out of the cells. SRL NCs decreased CD4+/CD8+ in normal mice after 14 days of daily gavage administration. Furthermore, SRL NCs enhanced the immune tolerance in an ovalbumin (OVA)-sensitized mouse model. SRL NCs significantly increased the percentage of Tregs (CD25+Foxp3+) among CD4+T cells. Collectively, these findings demonstrate that nanocrystallization of SRL enhances oral bioavailability, transcytosis, and prolongs drug residence time in vivo, while also enhancing SRL efficacy.

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