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1.
Front Pharmacol ; 15: 1437515, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055490

RESUMO

Introduction: Icaritin (ICT), a promising anti-hepatocellular carcinoma (HCC) prenylated flavonoid, is hindered from being applied due to its low water solubility and high lipophilicity in poorly differentiated HCC which is associated with upregulation of CD44 isoforms. Thus, hyaluronic acid (HA), a natural polysaccharide with high binding ability to CD44 receptors, was used to formulate a modified liposome as a novel targeted ICT-delivery system for HCC treatment. Methods: The ICT-Liposomes (Lip-ICT) with and without HA were prepared by a combined method of thin-film dispersion and post-insertion. The particle size, polydispersity (PDI), zeta potential, encapsulation efficacy (%EE), drug loading content (%DLC), and in vitro drug release profiles were investigated for physicochemical properties, whereas MTT assay was used to assess cytotoxic effects on HCC cells, HepG2, and Huh7 cells. Tumor bearing nude mice were used to evaluate the inhibitory effect of HA-Lip-ICT and Lip-ICT in vivo. Results: Lip-ICT and HA-Lip-ICT had an average particle size of 171.2 ± 1.2 nm and 208.0 ± 3.2 nm, with a zeta potential of -13.9 ± 0.83 and -24.8 ± 0.36, respectively. The PDI resulted from Lip-ICT and HA-Lip-ICT was 0.28 ± 0.02 and 0.26 ± 0.02, respectively. HA-Lip-ICT demonstrated higher in vitro drug release when pH was dropped from 7.4 to 5.5, The 12-h release rate of ICT from liposomes increased from 30% at pH7.4 to more than 60% at pH5.5. HA-Lip-ICT displayed higher toxicity than Lip-ICT in both HCC cells, especially Huh7with an IC50 of 34.15 ± 2.11 µM. The in vivo tissue distribution and anti-tumor experiments carried on tumor bearing nude mice indicated that HA-Lip- ICT exhibited higher tumor accumulation and achieved a tumor growth inhibition rate of 63.4%. Discussion: The nano-sized Lip-ICT was able to prolong the drug release time and showed long-term killing HCC cells ability. Following conjugation with HA, HA-Lip-ICT exhibited higher cytotoxicity, stronger tumor targeting, and tumor suppression abilities than Lip-ICT attributed to HA-CD44 ligand-receptor interaction, increasing the potential of ICT to treat HCC.

2.
Plant J ; 119(4): 2001-2020, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38943614

RESUMO

While it is known that increased dissolved CO2 concentrations and rising sea surface temperature (ocean warming) can act interactively on marine phytoplankton, the ultimate molecular mechanisms underlying this interaction on a long-term evolutionary scale are relatively unexplored. Here, we performed transcriptomics and quantitative metabolomics analyses, along with a physiological trait analysis, on the marine diatom Thalassiosira weissflogii adapted for approximately 3.5 years to warming and/or high CO2 conditions. We show that long-term warming has more pronounced impacts than elevated CO2 on gene expression, resulting in a greater number of differentially expressed genes (DEGs). The largest number of DEGs was observed in populations adapted to warming + high CO2, indicating a potential synergistic interaction between these factors. We further identified the metabolic pathways in which the DEGs function and the metabolites with significantly changed abundances. We found that ribosome biosynthesis-related pathways were upregulated to meet the increased material and energy demands after warming or warming in combination with high CO2. This resulted in the upregulation of energy metabolism pathways such as glycolysis, photorespiration, the tricarboxylic acid cycle, and the oxidative pentose phosphate pathway, as well as the associated metabolites. These metabolic changes help compensate for reduced photochemical efficiency and photosynthesis. Our study emphasizes that the upregulation of ribosome biosynthesis plays an essential role in facilitating the adaptation of phytoplankton to global ocean changes and elucidates the interactive effects of warming and high CO2 on the adaptation of marine phytoplankton in the context of global change.


Assuntos
Dióxido de Carbono , Diatomáceas , Diatomáceas/metabolismo , Diatomáceas/genética , Diatomáceas/fisiologia , Dióxido de Carbono/metabolismo , Fitoplâncton/genética , Fitoplâncton/fisiologia , Fitoplâncton/metabolismo , Adaptação Fisiológica , Transcriptoma , Aquecimento Global , Fotossíntese , Metabolômica
3.
Adv Healthc Mater ; 13(18): e2304261, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38482944

RESUMO

Defects in autophagy contribute to neurological deficits and motor dysfunction after spinal cord injury. Here a nanosystem is developed to deliver autophagy-promoting, anti-inflammatory drugs to nerve cells in the injured spinal cord. Celastrol, metformin, and everolimus as the mTOR inhibitor are combined into the zein-based nanoparticles, aiming to solubilize the drugs and prolong their circulation. The nanoparticles are internalized by BV2 microglia and SH-SY5Y neuron-like cells in culture; they inhibit the secretion of inflammatory factors by BV2 cells after insult with lipopolysaccharide, and they protect SH-SY5Y cells from the toxicity of H2O2. In a rat model of spinal cord injury, the nanoparticles mitigate inflammation and promote spinal cord repair. In the in vitro and in vivo experiments, the complete nanoparticles function better than the free drugs or nanoparticles containing only one or two drugs. These results suggest that the triple-drug nanoparticles show promise for treating spinal cord injury.


Assuntos
Anti-Inflamatórios , Nanopartículas , Regeneração Nervosa , Traumatismos da Medula Espinal , Zeína , Animais , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Nanopartículas/química , Regeneração Nervosa/efeitos dos fármacos , Zeína/química , Ratos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Humanos , Ratos Sprague-Dawley , Metformina/farmacologia , Metformina/química , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/química , Camundongos , Linhagem Celular , Microglia/efeitos dos fármacos , Microglia/metabolismo , Autofagia/efeitos dos fármacos
4.
ACS Nano ; 18(12): 8934-8951, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38483284

RESUMO

Spinal cord injury is a disease that causes severe damage to the central nervous system. Currently, there is no cure for spinal cord injury. Azithromycin is commonly used as an antibiotic, but it can also exert anti-inflammatory effects by down-regulating M1-type macrophage genes and up-regulating M2-type macrophage genes, which may make it effective for treating spinal cord injury. Bone mesenchymal stem cells possess tissue regenerative capabilities that may help promote the repair of the injured spinal cord. In this study, our objective was to explore the potential of promoting repair in the injured spinal cord by delivering bone mesenchymal stem cells that had internalized nanoparticles preloaded with azithromycin. To achieve this objective, we formulated azithromycin into nanoparticles along with a trans-activating transcriptional activator, which should enhance nanoparticle uptake by bone mesenchymal stem cells. These stem cells were then incorporated into an injectable hydrogel. The therapeutic effects of this formulation were analyzed in vitro using a mouse microglial cell line and a human neuroblastoma cell line, as well as in vivo using a rat model of spinal cord injury. The results showed that the formulation exhibited anti-inflammatory and neuroprotective effects in vitro as well as therapeutic effects in vivo. These results highlight the potential of a hydrogel containing bone mesenchymal stem cells preloaded with azithromycin and trans-activating transcriptional activator to mitigate spinal cord injury and promote tissue repair.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Ratos , Humanos , Animais , Hidrogéis/farmacologia , Azitromicina/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal , Anti-Inflamatórios/farmacologia
5.
Int J Nanomedicine ; 18: 6639-6665, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026538

RESUMO

Honokiol (HNK) is a small-molecule polyphenol that has garnered considerable attention due to its diverse pharmacological properties, including antitumor, anti-inflammatory, anti-bacterial, and anti-obesity effects. However, its clinical application is restricted by challenges such as low solubility, poor bioavailability, and rapid metabolism. To overcome these limitations, researchers have developed a variety of nano-formulations for HNK delivery. These nano-formulations offer advantages such as enhanced solubility, improved bioavailability, extended circulation time, and targeted drug delivery. However, existing reviews of HNK primarily focus on its clinical and pharmacological features, leaving a gap in the comprehensive evaluation of HNK delivery systems based on nanotechnology. This paper aims to bridge this gap by comprehensively reviewing different types of nanomaterials used for HNK delivery over the past 15 years. These materials encompass vesicle delivery systems, nanoparticles, polymer micelles, nanogels, and various other nanocarriers. The paper details various HNK nano-delivery strategies and summarizes their latest applications, development prospects, and future challenges. To compile this review, we conducted an extensive search using keywords such as "honokiol", "nanotechnology", and "drug delivery system" on reputable databases, including PubMed, Scopus, and Web of Science, covering the period from 2008 to 2023. Through this search, we identified and selected approximately 90 articles that met our specific criteria.


Assuntos
Lignanas , Nanopartículas , Sistemas de Liberação de Medicamentos , Compostos de Bifenilo/farmacologia , Micelas , Nanotecnologia , Lignanas/farmacologia
6.
J Clin Ultrasound ; 51(9): 1615-1621, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37680166

RESUMO

BACKGROUND: The expression of the Bcl-2 protein is frequently observed in basal cell carcinomas (BCCs), making it a significant biological marker and potential therapeutic target. Skin ultrasonography offers a noninvasive means of obtaining anatomical information about cutaneous tumors. OBJECTIVES: The purpose of this study was to investigate the correlation between ultrasound features and Bcl-2 expression in BCCs, to provide a reference for developing pharmacological treatment plans. METHODS: According to the Bcl-2 protein expression, 74 BCCs confirmed by surgical pathology were divided into high Bcl-2 expression BCCs (HB-BCCs) and low Bcl-2 expression BCCs (LB-BCCs). Preoperative lesion ultrasound features were analyzed retrospectively based on Liang's criteria, which included the following features: shape, surface, keratinization, base, infiltration level, internal echogenicity, distribution of hyperechoic spots, posterior echogenic changes, internal Doppler signal, and lesion size (maximum diameter and infiltration depth). The differences of two groups were compared using a chi-square test or a paired t-test. RESULTS: Based on ultrasound features, cystic areas were more frequent in LB-BCCs (χ2 = 7.015, P = .008). Furthermore, LB-BCCs exhibited greater infiltration depth than HB-BCCs (4.86 ± 2.12 mm vs. 2.72 ± 1.40 mm, P = .000), had a higher propensity to infiltrate the subcutaneous tissue (χ2 = 12.422, P = .002), and displayed a more abundant internal Doppler signal within the lesions (χ2 = 24.696, P = .000). Conversely, maximum diameter of the lesions, shape, surface, keratinization, base, hyperechoic spots distribution, and posterior echogenic changes of the lesions did not differ significantly between the two groups. CONCLUSIONS: Ultrasound features are correlated with Bcl-2 protein expression level in BCCs. LB-BCCs show greater infiltration depth, subcutaneous infiltration, more cystic changes and more abundant internal Doppler signal than HB-BCCs, which may suggest a potential basis for drug selection in BCC chemotherapy.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Estudos Retrospectivos , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Ultrassonografia
7.
Int J Nanomedicine ; 18: 5159-5181, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37705869

RESUMO

Background: Flurbiprofen axetil (FA) is a non-steroidal anti-inflammatory drug with good analgesic and anti-inflammatory effects. However, it suffers from poor solubility, short circulation time, and off-target binding profile, which significantly limit its clinical application. Here, we loaded FA into stealth lipid microspheres modified with the arginine-glycine-aspartic acid (RGD) peptide (cRGD-FA-SLM), and examined the therapeutic potential of the resulting platform for the treatment of rheumatoid arthritis (RA). Methods: cRGD-FA-SLM was prepared by high pressure homogenization, and its toxicity and uptake by macrophages were examined using cultures of RAW264.7 cells. Hemolysis and hepatotoxicity tests were performed to assess the safety of the developed platform, while its pharmacokinetics, biodistribution, and therapeutic efficacy were investigated in a collagen-induced arthritis rat model. Results: cRGD-FA-SLM showed homogeneous spherical morphology and efficient encapsulation of FA. The developed platform was non-toxic to normal macrophages and was selectively internalized by lipopolysaccharide-activated macrophages in vitro, while it distributed mainly to arthritic joints and significantly prolonged FA in circulation in vivo. cRGD-FA-SLM also significantly reduced the expression of prostaglandin E2 and alleviated joint edema and bone erosion, showing prolonged analgesic effects in arthritic rats. Conclusion: cRGD-FA-SLM shows good inflammation-targeting ability and prolongs drug circulation in vivo, suggesting promise as an anti-inflammatory and analgesic agent for targeted RA treatment.


Assuntos
Artrite Reumatoide , Nanosferas , Animais , Ratos , Distribuição Tecidual , Artrite Reumatoide/tratamento farmacológico , Dinoprostona
8.
J Control Release ; 362: 356-370, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37541592

RESUMO

Photodynamic therapy, in which photosensitizers locally generate cytotoxic reactive oxygen species, can treat tumor tissue with minimal effects on surrounding normal tissue, but it can be ineffective because of the anoxic tumor microenvironment. Here we developed a strategy to inactivate the mitochondria of tumor cells in order to ensure adequate local oxygen concentrations for photodynamic therapy. We conjugated the photosensitizer 5-aminolevulinic acid to the lipophilic cation triphenylphosphine, which targets mitochondria. Then we packaged the conjugate into nanoparticles that were based on biocompatible bovine serum albumin and coated with folic acid in order to target the abundant folate receptors on the tumor surface. In studies in cell culture and BALB/c mice bearing MCF-7 xenografts, we found that the nanoparticles helped solubilize the cation-photosensitizer conjugate, prolong its circulation, and enhance its photodynamic antitumor effects. We confirmed the ability of the nanoparticles to target tumor cells and their mitochondria using confocal laser microscopy and in vivo assays of pharmacokinetics, pharmacodynamics, and tissue distribution. Our results not only identify a novel nanoparticle system for treating cancer, but they demonstrate the feasibility of enhancing photodynamic therapy by reducing oxygen consumption within tumors.

9.
Biomater Sci ; 11(17): 5984-6000, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37503566

RESUMO

Dental caries is a chronic oral disease that results from the demineralization of dental hard tissues caused by the long-term interaction of various pathogenic factors in the human oral cavity. Although magnolol (Mag) and fluconazole (FLC) have shown promising antibacterial activity against Candida albicans (C. albicans) and Streptococcus mutans (S. mutans), their clinical application is limited due to hydrophobicity. In this study, we constructed biomineral-binding liposomes co-loaded with Mag and FLC (PPi-Mag/FLC-LPs) to overcome the hydrophobicity and achieve a dual antibacterial activity in the acidic microenvironment of caries. PPi-Mag/FLC-LPs were characterized by laser particle size analysis, transmission electron microscopy, and high-performance liquid chromatography (HPLC). The ability of PPi-Mag/FLC-LPs to bind hydroxyapatite was assessed in vitro using fluorescence microscopy and HPLC, while the antibacterial activity was examined by measuring drug effects on the acidogenicity, acid resistance, biofilm formation and survival of C. albicans and S. mutans. The pharmacodynamics of PPi-Mag/FLC-LPs was also evaluated in vivo in a rat model of dental caries. Mag and FLC were released rapidly from PPi-Mag/FLC-LPs in a pH-sensitive manner, and they bound effectively to hydroxyapatite, leading to a better antibacterial effect on C. albicans and S. mutans compared to free drugs or liposomes loaded with a single drug. PPi-Mag/FLC-LPs improved the medicinal properties of Mag and FLC and provided a rapid, pH-sensitive release of both drugs in vitro. PPi-Mag/FLC-LPs displayed good antibacterial activity in vivo, showing promise as a dual-drug delivery system for the prevention and treatment of caries.


Assuntos
Cárie Dentária , Lipossomos , Humanos , Animais , Ratos , Lipossomos/farmacologia , Cárie Dentária/tratamento farmacológico , Cárie Dentária/prevenção & controle , Lipopolissacarídeos/farmacologia , Biofilmes , Antibacterianos/farmacologia , Candida albicans , Streptococcus mutans , Hidroxiapatitas
10.
Neurochem Res ; 48(3): 767-780, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36418652

RESUMO

Spinal cord injury (SCI) is a serious injury to the central nervous system that causes significant physical and psychological trauma to the patient. SCI includes primary spinal cord injuries and secondary spinal cord injuries. The secondary injury refers to the pathological process or reaction after the primary injury. Although SCI has always been thought to be an incurable injury, the human nerve has the ability to repair itself after an injury. However, the reparability is limited because glial scar formation impedes functional recovery. There is a type of astrocyte that can differentiate into two forms of reactive astrocytes known as 'A1' and 'A2' astrocytes. A1 astrocytes release cytotoxic chemicals that cause neurons and oligodendrocytes to die and perform a harmful role. A2 astrocytes can produce neurotrophic factors and act as neuroprotectors. This article discusses ways to block A1 astrocytes while stimulating A2 astrocytes to formulate a new treatment for spinal cord injury.


Assuntos
Astrócitos , Traumatismos da Medula Espinal , Humanos , Astrócitos/patologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Neurônios/patologia , Gliose/patologia , Sistema Nervoso Central , Medula Espinal/patologia
11.
Front Pharmacol ; 13: 1054803, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506573

RESUMO

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Sanguisorba officinalis L. (SOL), a traditional Chinese herbal medicine called Diyu, has been shown to have potent antitumor effects. However, the role of SOL in suppressing NSCLC remains unknown. Methods: Network pharmacology was employed for acquiring the potential targets and mechanisms of SOL in NSCLC. Based on the predictions of network pharmacology, we used CCK8 and EdU assays to investigate cell proliferation, flow cytometry to investigate apoptosis, wound healing assay to investigate cell migration, and transwell assay to investigate cell invasion in vitro. Western blot was employed for detecting the potential proteins, including signaling pathways and apoptosis. The A549-bearing athymic nude mice were employed to verify the effect on cell proliferation and apoptosis in vivo. Results: SOL significantly inhibited the proliferation, migration and invasion of NSCLC cells in a dose-dependent manner. Flow cytometry showed that the apoptotic ratio and ROS level of NSCLC cells increased significantly with increasing concentrations. AKT and the PI3K-AKT signaling pathway were analyzed as the most relevant target and pathway via network pharmacology predictions. Western blotting revealed that the expression levels of p-PI3K, p-AKT, and p-mTOR in NSCLC cells treated with SOL were significantly downregulated, while cleaved PARP-1 and caspase-3 were upregulated in a dose-dependent manner. The results in the mouse xenograft model were consistent with those in NSCLC cell lines. Conclusion: SOL downregulated the PI3K/AKT/mTOR signaling pathway to suppress NSCLC.

12.
Entropy (Basel) ; 24(11)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36359645

RESUMO

We present an alternative scheme to achieve Schrödinger cat states in a strong coupling hybrid cavity optomechanical system. Under the single-photon strong-coupling regime, the interaction between the atom-cavity-oscillator system can induce the mesoscopic mechanical oscillator to Schrödinger cat states. Comparing to previous schemes, the proposed proposal consider the second order approximation on the Lamb-Dicke parameter, which is more universal in the experiment. Numerical simulations confirm the validity of our derivation.

13.
Nanomedicine ; 41: 102526, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35104674

RESUMO

Spinal cord injury (SCI) often causes neuronal membrane rupture and immediate death of neurons, followed by complicated secondary injuries. Treatment of SCI still remains a major challenge in clinical practice; thus, a great advance is urgently needed in this field. Metformin (MET) has anti-oxidant, anti-inflammatory, anti-apoptotic and neuroprotective properties, which may exert a potential therapeutic effect on SCI. In this study, we established a zein-based MET-loaded nanodrug system (CAQK-MET-NPs) for the targeted drug delivery for SCI. The results showed that MET could be effectively encapsulated into zein to obtain the zein-based spherical nanoparticles. Pharmacokinetic analysis indicated that CAQK-MET-NPs exhibited sustained-release and long-term therapeutic effects. The fluorescence imaging and tissue distribution experiments showed that CAQK-MET-NPs could efficiently accumulate at the lesion site of SCI rats. In conclusion, CAQK-MET-NPs may be a promising nanodrug for the treatment of SCI.


Assuntos
Metformina , Nanopartículas , Traumatismos da Medula Espinal , Animais , Metformina/farmacologia , Metformina/uso terapêutico , Neurônios , Ratos , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Distribuição Tecidual
14.
Rev Sci Instrum ; 92(9): 095001, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598497

RESUMO

In the processing of particulate solids, particle-particle and particle-wall collisions can generate electrostatics. This is called contact/impact/frictional electrification and can lead to many problems such as affecting powder flow and explosion hazards. It is necessary to research the tribo-electrification charging due to single particle impacts on a target as the fundamental understanding of tribo-electrification. A new impact charging test rig based on an electrostatic sensor array that can measure charge transfer caused by a single impact between a particle and a target plane has been designed and established. Combined with the electrostatic sensor array, the compressed sensing algorithm is used to estimate not only the spatial position but also the charge amount of particle. The cross-correlation algorithm is used to determine particle's velocity instead of using other devices such as a photodetector. The new instrument allows single particles impacting target planes at different angles with a velocity exceeding 100 m/s. An oil calibration test rig has been constructed to verify the proposed methods. The estimation errors of the spatial position and charge amount are both within 5% when the particle is located at the central area of the pipeline and the estimation errors of velocities are within 2%. The impact charging experiments show a special initial charge prior to impact for which no net charge transfer would occur for polymer particles, but the charge would completely transfer for metal particles.

15.
J Nanobiotechnology ; 19(1): 329, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34666761

RESUMO

BACKGROUND: There is an obvious correlation between ulcerative colitis and colorectal cancer, and the risk of colorectal cancer in patients with ulcerative colitis is increasing. Therefore, the combination therapy of anti-inflammatory and anti-tumor drugs may show promising to inhibit colon cancer. 5-aminosalicylic acid (5-ASA) with anti-inflammatory function is effective for maintaining remission in patients with ulcerative colitis and may also reduce colorectal cancer risk. Histone deacetylase (HDAC) plays an essential role in the progression of colon cancer. Butyric acid (BA) is a kind of HDAC inhibitor and thus shows tumor suppression to colon cancer. However, the volatile and corrosive nature of BA presents challenges in practical application. In addition, its clinical application is limited due to its non-targeting ability and low bioavailability. We aimed to synthesize a novel dual-prodrug of 5-ASA and BA, referred as BBA, to synergistically inhibit colon cancer. Further, based on the fact that folate receptor (FR) is over-expressed in most solid tumors and it has been identified to be a cancer stem cell surface marker in colon cancer, we took folate as the targeting ligand and used carboxymethyl-ß-cyclodextrin (CM-ß-CD) to carry BBA and thus prepared a novel inclusion complex of BBA/FA-PEG-CM-ß-CD. RESULTS: It was found that BBA/FA-PEG-CM-ß-CD showed significant inhibition in cell proliferation against colon cancer cells SW620. It showed a pro-longed in vivo circulation and mainly accumulated in tumor tissue. More importantly, BBA/FA-PEG-CM-ß-CD gave great tumor suppression effect against nude mice bearing SW620 xenografts. CONCLUSIONS: Therefore, BBA/FA-PEG-CM-ß-CD may have clinical potential in colon cancer therapy.


Assuntos
Antineoplásicos , Neoplasias do Colo/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Pró-Fármacos , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Ácido Butírico/metabolismo , Ácido Butírico/farmacocinética , Ácido Butírico/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclodextrinas/química , Ácido Fólico/metabolismo , Masculino , Mesalamina/metabolismo , Mesalamina/farmacocinética , Mesalamina/farmacologia , Camundongos , Camundongos Nus , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia
16.
Sci Prog ; 104(2): 368504211023691, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34100331

RESUMO

This paper presents a study of aero-engine exhaust gas electrostatic sensor array to estimate the spatial position, charge amount and velocity of charged particle. Firstly, this study establishes a mathematical model to analyze the inducing characteristics and obtain the spatial sensitivity distribution of sensor array. Then, Tikhonov regularization and compressed sensing are used to estimate the spatial position and charge amount of particle based on the obtained sensitivity distribution; cross-correlation algorithm is used to determine particle's velocity. An oil calibration test rig is established to verify the proposed methods. Thirteen spatial positions are selected as the test points. The estimation errors of spatial positions and charge amounts are both within 5% when the particles are locating at central area. The errors are higher when the particles are closer to the wall and may exceed 10%. The estimation errors of velocities by using cross-correlation are all within 2%. An air-gun test rig is further established to simulate the high velocity condition and distinguish different kinds of particles such as metal particles and non-metal particles.

17.
J Control Release ; 335: 103-116, 2021 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-34015402

RESUMO

Tetramethylpyrazine (TMP) has been effectively used for treating spinal cord injury (SCI) due to its anti-inflammatory, antioxidant, and neuroprotective activity. However, its clinical application is limited due to poor water solubility and insufficient spinal cord targeting through the traditional dosage forms. Given that intravascular neutrophils are quickly recruited to the injury site as part of the inflammatory response in SCI, we conjugated the cell-penetrating HIV trans-activator of transcription (TAT) peptide to human serum albumin nanoparticles (NPs) to make a TMP delivery system (TAT-TMP-NPs) that could be internalized by neutrophils and delivered to SCI lesions. Results found that in SCI rats TAT-TMP-NPs promoted the recovery of locomotor function and the lesion area, while reducing the levels of inflammatory cytokines and oxidative stress-related factors. Safety evaluation and in vivo small-animal imaging showed that the cell-penetrating peptide TAT could enhance the uptake of TAT-TMP-NPs by neutrophils without being toxic to the body. TAT-TMP-NPs may overcome the poor water solubility and low bioavailability of TMP, showing promise for the clinical treatment of SCI.


Assuntos
Nanopartículas , Fármacos Neuroprotetores , Traumatismos da Medula Espinal , Animais , Pirazinas , Ratos , Ratos Sprague-Dawley , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico
18.
Int J Nanomedicine ; 16: 2703-2714, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854316

RESUMO

Macrophages have been extensively used in the development of drug delivery systems, as they can prolong the circulation and release of drugs, extend their half-life, increase their stability and targeting ability, and reduce immunogenicity. Moreover, they have good biocompatibility and degradability and offer abundant surface receptors for targeted delivery of a wide variety of drugs. Macrophage-mediated drug delivery systems can be prepared by loading drugs or drug-loaded nanoparticles into macrophages, macrophage membranes or macrophage-derived vesicles. Although such systems can be used to treat inflammation, cancer, HIV infection and other diseases, they require further research and optimization since they have been assembled from diverse sources and therefore can have quite different physical and chemical properties. Moreover, potential cell-drug interactions can limit their application, and the biological activity of membrane proteins might be lost during membrane extraction and storage. In this review, we summarize the recent advances in this field and discuss the preparation of macrophage-mediated drug delivery systems, their advantages over other delivery systems, their potential applications and future lines of research.


Assuntos
Sistemas de Liberação de Medicamentos , Macrófagos/metabolismo , Infecções por HIV/tratamento farmacológico , Humanos , Nanopartículas/química , Neoplasias/terapia , Terapia Fototérmica
19.
ACS Appl Mater Interfaces ; 13(8): 9643-9655, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33606494

RESUMO

Metal-organic frameworks (MOFs) are crystalline materials comprising metal centers and organic linkers that feature structural rigidity and functional flexibility. These attractive materials offer large surface areas, high porosity, and good chemical stability; they have shown promise in chemistry (H2 separation and catalysis), magnetism, and optics. They have also shown potential for drug delivery following the demonstration in 2006 that chromium-based MOFs can be loaded with ibuprofen. Since then, iron-based MOFs (Fe-MOFs) have been shown to offer high drug loading and excellent biocompatibility. The present review focuses on the synthesis and surface modifications of Fe-MOFs as well as their applications in drug delivery and biomedicine.


Assuntos
Portadores de Fármacos/química , Estruturas Metalorgânicas/química , Animais , Linhagem Celular Tumoral , Meios de Contraste/síntese química , Meios de Contraste/química , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Ferro/química , Estruturas Metalorgânicas/síntese química
20.
J Nanobiotechnology ; 19(1): 14, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413405

RESUMO

BACKGROUND: Nano-drug delivery systems show considerable promise for effective cancer therapy. Polymeric micelles have attracted extensive attention as practical nanocarriers for target drug delivery and controlled drug delivery system, however, the distribution of micelles and the release of the drug are difficult to trace in cancer cells. Therefore, the construction of a redox-sensitive multifunctional drug delivery system for intelligent release of anticancer drugs and simultaneous diagnostic imaging and therapy remains an attractive research subject. RESULTS: To construct a smart drug delivery system for simultaneous imaging and cancer chemotherapy, mPEG-ss-Tripp was prepared and self-assembled into redox-sensitive polymeric micelles with a diameter of 105 nm that were easily detected within cells using confocal laser scanning microscopy based on aggregation-induced emission. Doxorubicin-loaded micelles rapidly released the drug intracellularly when GSH reduced the disulfide bond. The drug-loaded micelles inhibited tumor xenografts in mice, while this efficacy was lower without the GSH-responsive disulfide bridge. These results establish an innovative multi-functional polymeric micelle for intracellular imaging and redox-triggered drug deliver to cancer cells. CONCLUSIONS: A novel redox-sensitive drug delivery system with AIE property was constructed for simultaneous cellular imaging and intelligent drug delivery and release. This smart drug delivery system opens up new possibilities for multifunctional drug delivery systems.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Micelas , Polímeros/química , Animais , Sobrevivência Celular , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oxirredução
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