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1.
Artigo em Inglês | MEDLINE | ID: mdl-32429664

RESUMO

The development of a highly effective photosensitizer (PS) that can be activated with a low-power single light is a pressing issue. Herein, we report a PS for synergistic photodynamic and photothermal therapy constructed through self-assembly of poly(selenoviologen) on the surface of core-shell NaYF4:Yb/Tm@NaYF4 upconversion nanoparticles. The hybrid UCNPs/PSeV PS showed strong ROS generation ability and high photothermal conversion efficiency (~52.5%) under the mildest reported-to-date irradiation conditions (λ = 980 nm, 150 mW/cm2, 4 min), leading to the highly efficient in killing methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo. Remarkably, after intravenous injection, the reported PS accumulated preferentially in deep MRSA-infected tissues and achieved an excellent therapeutic index. This PS design realizes a low-power single NIR light triggered synergistic phototherapy and provides a simple and versatile strategy to develop safe clinically translatable agents for efficient treatment of deep tissue bacterial inflammations.

2.
Exp Cell Res ; : 112002, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32277958

RESUMO

AarF domain containing kinase 5 (ADCK5) is a member of an atypical kinase family and overexpressed in many carcinomas including lung cancer, while the function of this protein has not been elucidated. Here we investigated the mechanism of ADCK5 involved in regulating invasion and migration of lung cancer cells, and showed that ADCK5 might regulate the expression of tumor oncogene human pituitary tumor transforming gene-1 (PTTG1) by phosphorylating transcription factor SOX9, therefore enhancing the migration and invasion capabilities of lung cancer cells. Mutagenesis of potential serine phosphorylation sites on SOX9 indicated that serine 181 might be required to maintain transcription activation of SOX9 as well as increase PTTG1 levels. The serine 181 site of SOX9 is in a motif that is targeted by ADCK5. The ADCK5-SOX9-PTTG1 pathway might be a potential therapeutic target for lung cancer.

3.
Medicine (Baltimore) ; 99(17): e19480, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332600

RESUMO

BACKGROUND: The digestive tract malignancies are a series of malignant tumor with high morbidity and mortality. Traditional Chinese medicine (TCM) combined with chemotherapy drugs interventions have been applied for the treatment of malignant tumors in Asian countries for dacades. This study aimed to assess the effectiveness and safety on the combination of Kanglaite injection and fluorouracil-based chemotherapy for treating digestive tract malignancies. PURPOSE: To assess the effectiveness and safety on the combination of Kanglaite injection and fluorouracil-based chemotherapy for digestive tract malignancies. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed when conducting the meta-analysis. Randomized controlled trials (RCTs) of Kanglaite injection combined with fluorouracil-based chemotherapy in the treatment of digestive tract malignant tumors were selected and assessed for inclusion. RevMan 5.3 software (Cochrane Collaboration, Oxford, UK) was used for meta-analysis. The objective response rate (ORR) was defined as the primary endpoint, and the disease control rate (DCR), quality of life (QoL), and toxicities were the secondary outcomes. RESULTS: 20 RCTs enrolling 1339 patients with advanced digestive tract malignancies were included. The methodological quality of most included trials was low to moderate. Compared with fluorouracil-based chemotherapy alone, Kanglaite injection plus fluorouracil-based chemotherapy can improve DCR (risk ratio (RR) = 1.18, 95% confidence interval (CI) 1.11-1.25, P < .00001), ORR (RR = 1.35, 95% CI 1.18-1.54, P < .00001), QoL (RR = 1.58, 95% CI 1.35-1.85, P < .00001), and can reduce adverse drug reactions (ADRs) such as myelosuppression (RR = 0.33, 95% CI 0.25-0.43, P < .00001), leukopenia (RR = 0.31, 95% CI 0.22-0.43, P < .00001), thrombocytopenia (RR = 0.6, 95% CI 0.38-0.49, P = .03), neutropenia (RR = 0.26, 95% CI 0.12-0.55, P = .0005), anemia (RR = 0.41, 95% CI 0.23-0.75, P = .004), gastrointestinal reaction (RR = 0.35, 95% CI 0.27-0.46, P < .00001), nausea/vomiting (RR = 0.41, 95% CI 0.28-0.61, P < .00001), diarrhea (RR = 0.34, 95% CI 0.18-0.62, P = .0004), hepatotoxicity (RR = 0.28, 95% CI 0.17-0.47, P < .00001), neurotoxicity (RR = 0.58, 95% CI 0.41-0.82, P = .002), mucositis (RR = 0.59, 95% CI 0.29-1.21, P = .15). CONCLUSION: Kanglaite injection combined with fluorouracil-based chemotherapy could remarkably improve the clinical effectiveness and reduce the adverse effects in patients with advanced malignant tumors of the digestive tract which may provide evidence to judge whether TCM is an effective and safe intervention for the digestive tract malignancies.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Digestório/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fluoruracila/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Estadiamento de Neoplasias , Razão de Chances
4.
Gene Ther ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341485

RESUMO

Cardiovascular disease has become a major disease affecting health in the whole world. Gene therapy, delivering foreign normal genes into target cells to repair damages caused by defects and abnormal genes, shows broad prospects in treating different kinds of cardiovascular diseases. China has achieved great progress of basic gene therapy researches and pathogenesis of cardiovascular diseases in recent years. This review will summarize the latest research about gene therapy of proteins, epigenetics, including noncoding RNAs and genome-editing technology in myocardial infarction, cardiac ischemia-reperfusion injury, atherosclerosis, muscle atrophy, and so on in China. We wish to highlight some important findings about the essential roles of basic gene therapy in this field, which might be helpful for searching potential therapeutic targets for cardiovascular disease.

5.
Adv Exp Med Biol ; 1228: 395-408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32342473

RESUMO

The profound effect of exercise on the normal functioning of the immune system has been well-known. Exercise and immune regulation are interrelated and affect each other. Exercise changes immune regulation by affecting leucocytes, red blood cells, and cytokines, etc. Regular exercise could reduce the risk of chronic metabolic and cardiorespiratory diseases, partially by the anti-inflammatory effects of exercise. However, these effects are also likely to be responsible for the suppressed immunity that make our bodies more susceptible to infections. Here we summarize the known mechanisms by which exercise-both acute and chronic-exerts its immune regulation effects.

6.
Adv Exp Med Biol ; 1229: 149-161, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32285410

RESUMO

Non-coding RNA (ncRNA) is a class of RNAs that are not act as translational protein templates. They are involved in the regulation of gene transcription, RNA maturation and protein translation, participating in a variety of physiological and physiological processes. NcRNAs have important functions, and are recently one of the hotspots in biomedical research. Cardiac hypertrophy is classified into physiological cardiac hypertrophy and pathological cardiac hypertrophy. Different from pathological cardiac hypertrophy, physiological cardiac hypertrophy usually developed during exercise, pregnancy, normal postnatal growth, accompanied with preservation or improvement of systolic function, while no cardiac fibrosis. In this chapter, we will briefly introduce the definition, characteristics, and functions of ncRNAs, including miRNAs, lncRNAs, and circRNAs, as well as a summary of the existing bioinformatics online databases which commonly used in the study of ncRNAs. Specially, this chapter will be focused on the characteristics and the underlying mechanisms about physiological cardiac hypertrophy. Furthermore, the regulatory mechanism of ncRNAs in physiological hypertrophy and the latest research progress will be summarized. Taken together, exploring physiologic cardiac hypertrophy-specific ncRNAs might be a unique research perspective that provides new point of view for interventions in heart failure and other cardiovascular diseases.

7.
Adv Exp Med Biol ; 1229: 247-258, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32285416

RESUMO

Aging is an important risk factor for cardiovascular diseases. Aging increasing the morbidity and mortality in cardiovascular disease patients. With the society is aging rapidly in the world, medical burden of aging-related cardiovascular diseases increasing drastically. Hence, it is urgent to explore the underlying mechanism and treatment of cardiac aging. Noncoding RNAs (ncRNAs, including microRNAs, long noncoding RNAs and circular RNAs) have been reported to be involved in many pathological processes, including cell proliferation, cell death differentiation, hypertrophy and aging in wide variety of cells and tissues. In this chapter, we will summarize the physiology and molecular mechanisms of cardiac aging. Then, the recent research advances of ncRNAs in cardiac aging will be provided. The lessons learned from ncRNAs and cardiac aging studies would bring new insights into the regulatory mechanisms ncRNAs as well as treatment of aging-related cardiovascular diseases.

8.
Adv Exp Med Biol ; 1229: 357-367, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32285424

RESUMO

The discovery of noncoding RNAs (ncRNAs) including short microRNAs, long ncRNAs and circular RNAs has broaden our knowledge about mammalian genomes and transcriptomes. A growing number of evidence on aberrantly regulated ncRNAs in cardiovascular diseases has indicated that ncRNAs are critical contributors to cardiovascular pathophysiology. Moreover, multiple recent studies have reported that ncRNAs can be detected in the bloodstream that differs between health subjects and diseased patients and some of them are remarkably stable. Although our knowledge about the origin and function of the circulating ncRNAs is still limited, these molecules have been regarded as promising noninvasive biomarker for risk stratification, diagnosis and prognosis of various cardiovascular diseases. In this chapter, we have described biological characteristics of circulating ncRNAs and discussed current trends and future prospects for the usage of circulating ncRNAs as biomarkers for common cardiovascular diseases.

9.
FEMS Microbiol Lett ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286617

RESUMO

Carbapenem resistance in Enterobacteriaceae members has become a major challenge, and the genetic environment of blaKPC, encoding Klebsiella pneumoniae carbapenemases, has not been fully clarified in China. In this study, we aimed to explore the genetic environment of blaKPC in 25 carbapenem-resistant E. coli isolates from hospitals in Hangzhou Province, China. Antimicrobial susceptibility against 22 common antimicrobial agents was tested. Polymerase chain reaction (PCR) analysis was performed for screening of the resistent genes, such as blaKPC, blaCTX-M, blaTEM, blaSHV, blaNDM, qnrA, qnrB, qnrS, aac(6')-Ib, armA and rmtB. The genetic environment of blaKPC were determinedin one isolate. blaKPC was detected by PCR in all the clinical E. coli isolates. There were no strains carrying blaNDM, qnrA, and armA. The genetic environment of blaKPC showed that blaKPC dissemination is plasmid mediated and that it is located in the Tn3-Tn4401 transposon complex. Encoding of blaKPC-2 was responsible for carbapenem resistance in the 25 E. coli isolates. The genetic environment of blaKPC was characterized by the Tn3-Tn4401 complex. Our findings may provide a theoretical basis for clinical drug-resistance monitoring, anti-infection treatment, and hospital infection control.

10.
Abdom Radiol (NY) ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32277241

RESUMO

PURPOSE: To determine the safety and efficacy of percutaneous intraductal radiofrequency ablation (RFA) combined with biliary metal stent placement for patients with unresectable malignant biliary obstruction. METHODS: From a cohort of 70 patients with unresectable malignant biliary obstruction, 28 patients received percutaneous intraductal RFA combined with biliary stent placement (group A) and the remaining 42 were treated with biliary metal stent placement only (group B). Stent patency, overall survival (OS), alleviation of jaundice, and postoperative complications were assessed. RESULTS: The technical success rate for both groups was 100%. No severe complications (e.g., biliary bleeding, perforation) occurred. In both groups, jaundice was relieved and the decrease of the total and direct bilirubin concentration was significant (p < 0.01). The median time of stent patency in group A and group B were 6.6 ± 0.3 months (95% CI 6.1-7.1 months) and 4.9 ± 0.4 months (95% CI 4.2-5.6 months), respectively (p < 0.01). The median overall survival times in Group A were 7.2 ± 0.3 months (95% CI 6.5-7.9 months) versus 5.6 ± 0.4 months (95% CI 4.8-6.4 months) in group B (p < 0.01). In univariate and multivariate analyses, intraductal RFA, stent patency, and decreased baseline serum direct bilirubin concentration were associated with greater OS (p < 0.05). CONCLUSION: Percutaneous intraductal RFA combined with stent placement is a safe and effective method for patients with malignant biliary obstruction. As compared to stent placement alone, percutaneous intraductal RFA can significantly prolong stent patency and improve the overall survival of patients with malignant biliary obstruction.

11.
FEBS J ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32243091

RESUMO

Cholesterol efflux from macrophages is the initial step of reverse cholesterol transport, an important process for high-density lipoprotein-mediated atheroprotection. G protein-coupled receptor (GPR) 120, which functions as long-chain fatty acid receptor, is well known for its anti-inflammatory and insulin-sensitizing function in macrophages. However, the role of GPR120 on macrophage foam cell formation, the hallmark of atherosclerotic plaques, has not been verified. In this study, we found for the first time that stimulation of GPR120 by its agonist GW9508 elevated the expression of ATP-binding cassette transporters (ABC) A1 and ABCG1 in THP-1 macrophage-derived foam cells and Raw264.7 macrophages, and promoted ABCA1- and ABCG1-mediated cholesterol efflux and reduced cellular cholesteryl ester (CE) content as well. In addition, GPR120 activation was accompanied with the stimulation of AMPK pathway in macrophages; however, the effect of GPR120 on macrophage cholesterol efflux was largely abolished by AMPK inhibition. Moreover, the AMPK activity and the expression of ABCA1 and ABCG1 were markedly abrogated by knockdown of GPR120, or application of phospholipase C (PLC) inhibitor, calcium chelator, or CaMKK inhibitor. Because only free cholesterol can be effluxed from macrophages, we found that activation of AMPK could lead to increase both neutral CEs hydrolysis by upregulation of neutral cholesterol ester hydrolase expression and acid CEs hydrolysis by activation of ULK1. In conclusion, these results demonstrated that GPR120 facilitated ABCA1- and ABCG1-mediated cholesterol efflux through activation of PLC/Ca2+ /CaMKK/AMPK signaling pathway, which induced CE hydrolysis and elevated the expression of ABCA1 and ABCG1 in macrophages.

12.
Mol Cell ; 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32348779

RESUMO

Cas13 has demonstrated unique and broad utility in RNA editing, nucleic acid detection, and disease diagnosis; however, a constantly active Cas enzyme may induce unwanted effects. Bacteriophage- or prophage-region-encoded anti-CRISPR (acr) gene molecules provide the potential to control targeting specificity and potency to allow for optimal RNA editing and nucleic acid detection by spatiotemporally modulating endonuclease activities. Using integrated approaches to screen acrVI candidates and evaluate their effects on Cas13 function, we discovered a series of acrVIA1-7 genes that block the activities of Cas13a. These VI-A CRISPR inhibitors substantially attenuate RNA targeting and editing by Cas13a in human cells. Strikingly, type VI-A anti-CRISPRs (AcrVIAs) also significantly muffle the single-nucleic-acid editing ability of the dCas13a RNA-editing system. Mechanistically, AcrVIA1, -4, -5, and -6 bind LwaCas13a, while AcrVIA2 and -3 can only bind the LwaCas13-crRNA (CRISPR RNA) complex. These identified acr molecules may enable precise RNA editing in Cas13-based application and study of phage-bacterium interaction.

13.
J Autoimmun ; : 102463, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32303424

RESUMO

It has been reported that SARS-CoV-2 may use ACE2 as a receptor to gain entry into human cells, in a way similar to that of SARS-CoV. Analyzing the distribution and expression level of ACE2 may therefore help reveal underlying mechanisms of viral susceptibility and post-infection modulation. In this study, we utilized previously uploaded information on ACE2 expression in various conditions including SARS-CoA to evaluate the role of ACE2 in SARS-CoV and extrapolate that to COVID-19. We found that the expression of ACE2 in healthy populations and patients with underlying diseases was not significantly different. However, based on the elevated expression of ACE2 in cigarette smokers, we speculate that long-term smoking may be a risk factor for COVID-19. Analysis of ACE2 in SARS-CoV infected cells suggests that ACE2 is not only a receptor but is also involved in post-infection regulation, including immune response, cytokine secretion, and viral genome replication. Moreover, we constructed Protein-protein interaction (PPI) networks and identified hub genes in viral activity and cytokine secretion. Our findings may help clinicians and researchers gain more insight into the pathogenesis of SARS-CoV-2 and design therapeutic strategies for COVID-19.

14.
Neuromolecular Med ; 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32253686

RESUMO

Reactive oxygen species (ROS) are continuously produced as byproducts of aerobic metabolism. Oxidative stress (OS) plays an important role in the occurrence of several neurodegenerative diseases as well as aging because of the accumulation of ROS. Gnaq is a member of G protein α subunits. It has been reported that the expression level of Gnaq in the mouse forebrain cortex was significantly decreased with age in our previous study; therefore, we supposed that Gnaq contributes to attenuate the OS. In this study, we generated a Gnaq-overexpression cell using gene recombinant technique and lentivirus transfection technique in a neuron-like PC12 cell, and investigated whether Gnaq had antioxidant effects in PC12 cells treated with H2O2. The viability of cells, concentration of ROS, Nrf2 nuclear translocation, expression of antioxidant enzymes, activation of NF-κB and apoptosis were compared between Gnaq-PC12 cells and Vector-PC12 cells. Results showed that, compared with Vector-PC12 cells, the antioxidative ability of Gnaq-PC12 cells was significantly improved, while the ROS level in Gnaq-PC12 cells was significantly decreased. Nrf2 nuclear translocation was up-regulated and NF-κB nuclear translocation was down-regulated in Gnaq-PC12 cells after H2O2 treatment. The results suggest that Gnaq plays a crucial role in neuroprotection in PC12 cells. A possible mechanism for this would be that the overexpressed Gnaq enhances the antioxidative effect mediated by Nrf2 signal pathway and inhibits the cellular damaging effect through NF-κB signal pathway.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32180254

RESUMO

Ubiquitin C-terminal hydrolase-L3 (UCH-L3) is a deubiquitinase that has a crucial role in oncogenesis. This study was aimed to explore the biological function of UCH-L3 in non-small cell lung cancer (NSCLC). Bioinformatics analysis was used to detect UCH-L3 expression in NSCLC tissues and normal lung tissues, and to analyze the relationship between UCH-L3 expression and survival of patients. qRT-PCR and western blotting assays were used to detect UCH-L3 expression in NSCLC tumor tissues and adjacent normal tissues. CCK-8 assay was performed to examine the effect of UCH-L3 on NSCLC cell proliferation. Flow cytometry assay was conducted to examine the effect of UCH-L3 on NSCLC cell cycle and apoptosis. The expression of UCH-L3 in NSCLC tissues was markedly higher than in normal lung tissues, and high expression of UCH-L3 was positively associated with the poor survival of patients. UCH-L3 knockdown significantly inhibited the proliferation of NSCLC cells, whereas UCH-L3 overexpression had the opposite effect. Moreover, UCH-L3 promoted NSCLC cells proliferation via accelerating cell cycle and inhibiting cell apoptosis. UCH-L3 is upregulated in NSCLC and positively associated with the poor survival, and its expression contributes to NSCLC cell proliferation by accelerating cell cycle and inhibiting cell apoptosis.

16.
ACS Appl Mater Interfaces ; 12(16): 18385-18394, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32212618

RESUMO

The development of novel applications of ultralong organic phosphorescent (UOP) materials is highly desired. Herein, a series of UOP materials (EDCz, E = O, S, Se, and Te) for bacterial afterglow imaging and photodynamic therapy (PDT) is reported. By structurally bonding with the chalcogen atoms with π-conjugated scaffolds, EDCz not only absorbs visible light but also emits UOP with an efficiency of ca. 0.01-6.8% and a long lifetime of 0.08-0.318 s under ambient conditions. Benefiting from the long-lived triplet excited states, the SeDCz nanocrystals (NCs) possessed the best optical properties in the series, generating 1O2 under white light irradiation and performing as an agent for Staphylococcus aureus afterglow imaging and PDT at a low concentration (98 ng mL-1). The SeDCz NCs are also utilized as real-time UOP imaging agents and promoted healing of infected wounds in living mice. To the best of our knowledge, this study presents the first example of UOP-based bacterial photodynamic theranostic agents and creates a platform for the next-generation efficient UOP-based photosensitizers for bioimaging and skin regeneration.

17.
Dalton Trans ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186311

RESUMO

Two chloroantimonate hybrids with isomeric bipyridyltriazoliums and similar packing patterns, {[2-bpt]2[(SbCl5)Cl2]}n (1) and {[4-bpt]2[(SbCl5)Cl2]}n (2) (2-bpt2+ = protonated 3,5-bis(pyridine-2-yl)-1,2,4-triazole, 4-bpt2+ = protonated 3,5-bis(pyridine-4-yl)-1,2,4-triazole), have been designed and synthesized. Distinct intermolecular electronic interactions and photochromic behaviors are attributed to the remarkable modulation of positional isomeric effect on the electron deficiency of the acceptors and donor-acceptor matching relationship. 1 is the first reported photochromic chloroantimonate hybrid.

18.
Biochem Biophys Res Commun ; 525(3): 706-713, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32139124

RESUMO

GGNBP1 is known as gametogenetin protein 1 (GGN1)-interacting protein. It is specifically expressed in the mitochondria of the testis, while its functional role during spermatogenesis is still unknown. Here, we showed that the disruption of Ggnbp1 resulted in abnormal spermiogenesis in around 40% mice, while the others show no defects in the genital system. Moreover, upon treatment with low dose of bisphenol A (BPA), Ggnbp1 knockout mice were more sensitive to environmental pollutant than control mice. The treatment led to decrease in sperm motility and production of abnormal spermatozoa. These results suggest that GGNBP1 mainly ensures proper spermiogenesis in response to various stresses in male mice.

19.
Mater Sci Eng C Mater Biol Appl ; 110: 110719, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32204031

RESUMO

Carbon quantum dots (Cdots) have attracted more and more interests in bioimaging and tumor theranostics. However, their practical application has been limited due to the small particle size and non-tumor-specific fluorescence. Here, reduction-cleavable disulfide-linked Cdots-based nanoclusters were fabricated to conjugate doxorubicin (DOX) via an acid-labile hydrazone bond. Owing to the pH and reduction dual-stimuli responsiveness, the proposed Cdots-based nanotheranostics possessed unique tumor-specific fluorescent property and tumor-specific controlled drug release performance, indicating their promising potential for the in-situ real-time fluorescent monitoring of therapeutic response in future tumor therapy.

20.
Mater Sci Eng C Mater Biol Appl ; 110: 110653, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32204081

RESUMO

Carbon quantum dots (CQDs) show promising potential for tumor imaging owing to their unique superior fluorescent properties. However, the small particle size limits their practical application. Here, pH/reduction dual-responsive comet-shaped PEGylated CQD-DOX conjugate prodrug, DOX-Hy-CQD-SS-PEG with DOX content of 28.5%, was designed with the hydrophobic acid-labile DOX conjugated CQDs as comet nucleus and the few hydrophilic bioreducible detachable PEG brushes as comet tails. The comet-shaped DOX-Hy-CQD-SS-PEG prodrug could self-assemble into unique micelles with mean diameter of 127 nm. The DOX-Hy-CQD-SS-PEG micelles possessed excellent pH/reduction dual-responsive drug release with low drug leakage of 9% in 150 h. Furthermore, the fluorescent CQDs was recovered after DOX release and de-PEGylation, demonstrating their potential application for real-time response of therapy.

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