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1.
ACS Appl Mater Interfaces ; 16(15): 18551-18563, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38564314

RESUMO

High levels of reactive oxygen species (ROS) are known to play a critical role in the secondary cascade of spinal cord injury (SCI). The scavenging of ROS has emerged as a promising approach for alleviating acute SCI. Moreover, identifying the precise location of the SCI site remains challenging. Enhancing the visualization of the spinal cord and improving the ability to distinguish the lesion site are crucial for accurate and safe treatment. Therefore, there is an urgent clinical need to develop a biomaterial that integrates diagnosis and treatment for SCI. Herein, ultra-small-sized gold nanodots (AuNDs) were designed for dual-mode imaging-guided precision treatment of SCI. The designed AuNDs demonstrate two important functions. First, they effectively scavenge ROS, inhibit oxidative stress, reduce the infiltration of inflammatory cells, and prevent apoptosis. This leads to a significant improvement in SCI repair and promotes a functional recovery after injury. Second, leveraging their excellent dual-mode imaging capabilities, the AuNDs enable rapid and accurate identification of SCI sites. The high contrast observed between the injured and adjacent uninjured areas highlights the tremendous potential of AuNDs for SCI detection. Overall, by integrating ROS scavenging and dual-mode imaging in a single biomaterial, our work on functionalized AuNDs provides a promising strategy for the clinical diagnosis and treatment of SCI.


Assuntos
Ouro , Traumatismos da Medula Espinal , Humanos , Espécies Reativas de Oxigênio , Ouro/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Estresse Oxidativo , Materiais Biocompatíveis/uso terapêutico
2.
Biomater Sci ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683548

RESUMO

Inhalable nanomedicines are increasingly being developed to optimise the pharmaceutical treatment of respiratory diseases. Large lipid-based nanosystems at the forefront of the inhalable nanomedicines development pipeline, though, have a number of limitations. The objective of this study was, therefore, to investigate the utility of novel small lipidated sulfoxide polymers based on poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA) as inhalable drug delivery platforms with tuneable membrane permeability imparted by differential albumin binding kinetics. Linear PMSEA (5 kDa) was used as a hydrophilic polymer backbone with excellent anti-fouling and stealth properties compared to poly(ethylene glycol). Terminal lipids comprising single (1C2, 1C12) or double (2C12) chain diglycerides were installed to provide differing affinities for albumin and, by extension, albumin trafficking pathways in the lungs. Albumin binding kinetics, cytotoxicity, lung mucus penetration and cellular uptake and permeability through key cellular barriers in the lungs were examined in vitro. The polymers showed good mucus penetration and no cytotoxicity over 24 h at up to 1 mg ml-1. While 1C2-showed no interaction with albumin, 1C12-PMSEA and 2C12-PMSEA bound albumin with KD values of approximately 76 and 10 µM, respectively. Despite binding to albumin, 2C12-PMSEA showed reduced cell uptake and membrane permeability compared to the smaller polymers and the presence of albumin had little effect on cell uptake and membrane permeability. While PMSEA strongly shielded these lipids from albumin, the data suggest that there is scope to tune the lipid component of these systems to control membrane permeability and cellular interactions in the lungs to tailor drug disposition in the lungs.

3.
ACS Nano ; 18(14): 10288-10301, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38556985

RESUMO

Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.


Assuntos
Ferroptose , Neoplasias , Radioterapia Guiada por Imagem , Humanos , Espécies Reativas de Oxigênio , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Apoptose , Peróxido de Hidrogênio , Linhagem Celular Tumoral
4.
Expert Opin Drug Deliv ; 21(1): 151-167, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38248870

RESUMO

OBJECTIVES: Nanomedicines are being actively developed as inhalable drug delivery systems. However, there is a distinct utility in developing smaller polymeric systems that can bind albumin in the lungs. We therefore examined the pulmonary pharmacokinetic behavior of a series of lipidated brush-PEG (5 kDa) polymers conjugated to 1C2, 1C12 lipid or 2C12 lipids. METHODS: The pulmonary pharmacokinetics, patterns of lung clearance and safety of polymers were examined in rats. Permeability through monolayers of primary human alveolar epithelia, small airway epithelia and lung microvascular endothelium were also investigated, along with lung mucus penetration and cell uptake. RESULTS: Polymers showed similar pulmonary pharmacokinetic behavior and patterns of lung clearance, irrespective of lipid molecular weight and albumin binding capacity, with up to 30% of the dose absorbed from the lungs over 24 h. 1C12-PEG showed the greatest safety in the lungs. Based on its larger size, 2C12-PEG also showed the lowest mucus and cell membrane permeability of the three polymers. While albumin had no significant effect on membrane transport, the cell uptake of C12-conjugated PEGs were increased in alveolar epithelial cells. CONCLUSION: Lipidated brush-PEG polymers composed of 1C12 lipid may provide a useful and novel alternative to large nanomaterials as inhalable drug delivery systems.


Assuntos
Polietilenoglicóis , Polímeros , Ratos , Humanos , Animais , Polímeros/química , Polietilenoglicóis/química , Peso Molecular , Sistemas de Liberação de Medicamentos , Pulmão/metabolismo , Lipídeos/química , Albuminas/metabolismo
5.
J Am Chem Soc ; 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37922243

RESUMO

Dynamic helical polymers can change their helicity according to external stimuli due to the low helix-inversion barriers, while helicity stabilization for polymers is important for applications in chiral recognition or chiral separations. Here, we present a convenient methodology to stabilize dynamic helical conformations of polymers through intramolecular cross-linking. Thermoresponsive dendronized poly(phenylacetylene)s (PPAs) carrying 3-fold dendritic oligoethylene glycol pendants containing cinnamate moieties were synthesized. These polymers exhibit typical features of dynamic helical structures in different solvents, that is, racemic contracted conformations in less polar organic solvents and predominantly one-handed stretched helical conformations in highly polar solvents. This dynamic helicity can be enhanced through selective solvation by increasing the polarity of the organic solvents or simply via their thermally mediated dehydration in water. However, through photocycloaddition of the cinnamate moieties between the neighboring pendants via UV irradiation, these dendronized PPAs adopt stable helical conformations either below or above their phase transition temperatures in water, and their helical conformations can even be retained in less polar organic solvents. Spectroscopic and atomic force microscopy measurements demonstrate that photocycloaddition between the cinnamate moieties occurs on the individual molecular level, and this is found to be helpful in restraining the photodegradation of the PPA backbones. Molecular dynamics simulations reveal that the spatial orientation of the pendants along the rigid polyene backbone is crucial for the photodimerization of cinnamates within one helix pitch.

6.
Expert Opin Drug Deliv ; 20(8): 1145-1155, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37535434

RESUMO

OBJECTIVES: Drug delivery systems typically show limited access to the lung interstitium and absorption after pulmonary delivery. The aim of this work was to undertake a proof-of-concept investigation into the potential of employing endogenous albumin and albumin absorption mechanisms in the lungs to improve lung interstitial access and absorption of inhaled drug delivery systems that bind albumin. METHODS: The permeability of human albumin (HSA) through monolayers of primary human alveolar epithelia, small airway epithelia, and microvascular endothelium were investigated. The pulmonary pharmacokinetics of bovine serum albumin (BSA) was also investigated in efferent caudal mediastinal lymph duct-cannulated sheep after inhaled aerosol administration. RESULTS: Membrane permeability coefficient values (Papp) of HSA increased in the order alveolar epithelia

Assuntos
Albuminas , Pulmão , Humanos , Animais , Ovinos , Pulmão/metabolismo , Albuminas/metabolismo , Sistemas de Liberação de Medicamentos , Aerossóis , Linfa/metabolismo
7.
Public Health Pract (Oxf) ; 6: 100412, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37576525

RESUMO

Objectives: This paper evaluates a collaborative intervention between public health professionals and local social media administrators, in which the social media site Facebook was used with a view to strengthening engagement with and, dissemination of, core messages and building trust and resilience within local communities during the COVID-19 pandemic. Study design: A qualitative design was used, exploring the research question: how does collaboration between public health professionals and local social network group administrators create community engagement during a global crisis? Methods: Fourteen semi-structured interviews were conducted with public health staff and online group administrators. Data was analysed using framework analysis. Results: Collaboration between public health professionals and local group administrators created both opportunities and challenges. Local group administrators had wide reach and trust within the local community, but message credibility was enhanced through local authority involvement. Such collaborations contain inherent tensions due to perceived risks to social capital and independence but can be successful if receiving strong risk-tolerant support from the local authority. Findings are discussed in the context of Bourdieu's theory of social capital to examine how public health information can be delivered by trusted social media actors in communication tailored to the local community. Conclusions: Social media provides new channels of communication for delivery of public health messages, enabling new ways of working which create long-term engagement and community building. Although the intervention was developed quickly in response to the COVID-19 pandemic, participants felt it could be mobilised to address a wider range of issues.

8.
Front Digit Health ; 5: 1130784, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37448835

RESUMO

The growing popularity of social media and its ubiquitous presence in our lives brings associated risks such as the spread of mis- and disinformation, particularly when these may be unregulated in times of global crises. Online communities are able to provide support by enabling connection with others and also provide great potential for dynamic interaction and timely dissemination of information compared with more traditional methods. This study evaluates interactions within the Essex Coronavirus Action/Support Facebook private group, which set out to prevent the spread of COVID-19 infection by informing Essex residents of guidance and helping vulnerable individuals. At the outset, 18 community administrators oversaw the group, which attracted approximately 37,900 members. Longitudinal Facebook group interactions across five periods spanning the UK lockdowns 2020-2021 were analysed using psychological discourse analysis and supplementary computed-mediated analysis to further explore sentiment and linguistic features. The findings endorsed that the group provided a protected space for residents to express their feelings in times of crises and an opportunity to address confusion and concern. The effective communication of public health messages was facilitated by promoting desired interaction and the construction of group identities. Administrators worked with group members to achieve a shared understanding of others' perspectives and the COVID-19 evidence base, which led to a mobilisation of the provision of support in the community. This was accomplished through the application of rhetorical and interactional devices. This study demonstrates how online groups can employ discursive strategies to engage audiences, build cohesion, provide support, and encourage health protective behaviours. This has implications for public health teams in terms of designing, implementing, or evaluating such interventions.

9.
ACS Nano ; 17(9): 8483-8498, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37097065

RESUMO

Cancer theranostics that combines cancer diagnosis and therapy is a promising approach for personalized cancer treatment. However, current theranostic strategies suffer from low imaging sensitivity for visualization and an inability to target the diseased tissue site with high specificity, thus hindering their translation to the clinic. In this study, we have developed a tumor microenvironment-responsive hybrid theranostic agent by grafting water-soluble, low-fouling fluoropolymers to pH-responsive zeolitic imidazolate framework-8 (ZIF-8) nanoparticles by surface-initiated RAFT polymerization. The conjugation of the fluoropolymers to ZIF-8 nanoparticles not only allows sensitive in vivo visualization of the nanoparticles by 19F MRI but also significantly prolongs their circulation time in the bloodstream, resulting in improved delivery efficiency to tumor tissue. The ZIF-8-fluoropolymer nanoparticles can respond to the acidic tumor microenvironment, leading to progressive degradation of the nanoparticles and release of zinc ions as well as encapsulated anticancer drugs. The zinc ions released from the ZIF-8 can further coordinate to the fluoropolymers to switch the hydrophilicity and reverse the surface charge of the nanoparticles. This transition in hydrophilicity and surface charge of the polymeric coating can reduce the "stealth-like" nature of the agent and enhance specific uptake by cancer cells. Hence, these hybrid nanoparticles represent intelligent theranostics with highly sensitive imaging capability, significantly prolonged blood circulation time, greatly improved accumulation within the tumor tissue, and enhanced anticancer therapeutic efficiency.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Neoplasias , Humanos , Polímeros de Fluorcarboneto/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanopartículas/uso terapêutico , Imageamento por Ressonância Magnética , Interações Hidrofóbicas e Hidrofílicas , Zinco/uso terapêutico , Íons , Microambiente Tumoral
10.
Adv Drug Deliv Rev ; 197: 114822, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37086918

RESUMO

Central nervous system (CNS) disorders affect as many as 1.5 billion people globally. The limited delivery of most imaging and therapeutic agents into the brain is a major challenge for treatment of CNS disorders. With the advent of nanotechnologies, controlled delivery of drugs with nanoparticles holds great promise in CNS disorders for overcoming the blood-brain barrier (BBB) and improving delivery efficacy. In recent years, magnetic iron oxide nanoparticles (MIONPs) have stood out as a promising theranostic nanoplatform for brain imaging and drug delivery as they possess unique physical properties and biodegradable characteristics. In this review, we summarize the recent advances in MIONP-based platforms as imaging and drug delivery agents for brain diseases. We firstly introduce the methods of synthesis and surface functionalization of MIONPs with emphasis on the inclusion of biocompatible polymers that allow for the addition of tailored physicochemical properties. We then discuss the recent advances in in vivo imaging and drug delivery applications using MIONPs. Finally, we present a perspective on the remaining challenges and possible future directions for MIONP-based brain delivery systems.


Assuntos
Doenças do Sistema Nervoso Central , Nanopartículas , Humanos , Sistemas de Liberação de Medicamentos/métodos , Encéfalo/diagnóstico por imagem , Barreira Hematoencefálica , Nanopartículas Magnéticas de Óxido de Ferro , Preparações Farmacêuticas , Doenças do Sistema Nervoso Central/tratamento farmacológico , Nanopartículas/uso terapêutico , Neuroimagem
11.
Nat Commun ; 14(1): 1025, 2023 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-36823106

RESUMO

Glucocorticoids prescribed to limit inflammation, have significant adverse effects. As 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) regenerates active glucocorticoid, we investigated whether 11ß-HSD1 inhibition with AZD4017 could mitigate adverse glucocorticoid effects without compromising their anti-inflammatory actions. We conducted a proof-of-concept, randomized, double-blind, placebo-controlled study at Research Unit, Churchill Hospital, Oxford, UK (NCT03111810). 32 healthy male volunteers were randomized to AZD4017 or placebo, alongside prednisolone treatment. Although the primary endpoint of the study (change in glucose disposal during a two-step hyperinsulinemic, normoglycemic clamp) wasn't met, hepatic insulin sensitivity worsened in the placebo-treated but not in the AZD4017-treated group. Protective effects of AZD4017 on markers of lipid metabolism and bone turnover were observed. Night-time blood pressure was higher in the placebo-treated but not in the AZD4017-treated group. Urinary (5aTHF+THF)/THE ratio was lower in the AZD4017-treated but remained the same in the placebo-treated group. Most anti-inflammatory actions of prednisolone persisted with AZD4017 co-treatment. Four adverse events were reported with AZD4017 and no serious adverse events. Here we show that co-administration of AZD4017 with prednisolone in men is a potential strategy to limit adverse glucocorticoid effects.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1 , Anti-Inflamatórios , Prednisolona , Humanos , Masculino , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Anti-Inflamatórios/efeitos adversos , Glucocorticoides/efeitos adversos , Inflamação/tratamento farmacológico , Prednisolona/efeitos adversos
12.
Angew Chem Int Ed Engl ; 61(49): e202213071, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36225164

RESUMO

Efficient removal of per- and polyfluoroalkyl substances (PFAS) from contaminated waters is urgently needed to safeguard public and environmental health. In this work, novel magnetic fluorinated polymer sorbents were designed to allow efficient capture of PFAS and fast magnetic recovery of the sorbed material. The new sorbent has superior PFAS removal efficiency compared with the commercially available activated carbon and ion-exchange resins. The removal of the ammonium salt of hexafluoropropylene oxide dimer acid (GenX) reaches >99 % within 30 s, and the estimated sorption capacity was 219 mg g-1 based on the Langmuir model. Robust and efficient regeneration of the magnetic polymer sorbent was confirmed by the repeated sorption and desorption of GenX over four cycles. The sorption of multiple PFAS in two real contaminated water matrices at an environmentally relevant concentration (1 ppb) shows >95 % removal for the majority of PFAS tested in this study.


Assuntos
Fluorocarbonos , Poluentes Químicos da Água , Fluorocarbonos/química , Poluentes Químicos da Água/química , Adsorção , Polímeros de Fluorcarboneto , Fenômenos Magnéticos , Água
13.
Adv Sci (Weinh) ; 9(35): e2204476, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36316248

RESUMO

Quantum dots (QDs) of formamidinium lead triiodide (FAPbI3 ) perovskite hold great potential, outperforming their inorganic counterparts in terms of phase stability and carrier lifetime, for high-performance solar cells. However, the highly dynamic nature of FAPbI3 QDs, which mainly originates from the proton exchange between oleic acid and oleylamine (OAm) surface ligands, is a key hurdle that impedes the fabrication of high-efficiency solar cells. To tackle such an issue, here, protonated-OAm in situ to strengthen the ligand binding at the surface of FAPbI3 QDs, which can effectively suppress the defect formation during QD synthesis and purification processes is selectively introduced. In addition, by forming a halide-rich surface environment, the ligand density in a broader range for FAPbI3 QDs without compromising their structural integrity, which significantly improves their optoelectronic properties can be modulated. As a result, the power conversion efficiency of FAPbI3 QD solar cells (QDSCs) is enhanced from 7.4% to 13.8%, a record for FAPbI3 QDSCs. Furthermore, the suppressed proton exchange and reduced surface defects in FAPbI3 QDs also enhance the stability of QDSCs, which retain 80% of the initial efficiency upon exposure to ambient air for 3000 hours.

14.
Biomacromolecules ; 23(10): 4318-4326, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-36048616

RESUMO

Non-thrombogenic surfaces for extracorporeal membrane oxygenation (ECMO) devices are important to increase their duration of usage and to enable long-term life support. However, the contact of blood with the hydrophobic synthetic ECMO membrane materials such as poly(4-methyl-1-pentene) (PMP) can activate the coagulation cascade, causing thrombosis and a series of consequent complications during ECMO operation. Targeting this problem, we proposed to graft highly hydrophilic sulfoxide polymer brushes onto the PMP surfaces via gamma ray irradiation-initiated polymerization to improve the hemocompatibility of the membrane. Through this chemical modification, the surface of the PMP film is altered from hydrophobic to hydrophilic. The extent of plasma protein adsorption and platelet adhesion, the prerequisite mediators of the coagulation cascade and thrombus formation, are drastically reduced compared with those of the unmodified PMP film. Therefore, the method provides a facile approach to modify PMP materials with excellent antifouling properties and improved hemocompatibility demanded by the applications in ECMO and other blood-contacting medical devices.


Assuntos
Incrustação Biológica , Oxigenação por Membrana Extracorpórea , Incrustação Biológica/prevenção & controle , Proteínas Sanguíneas , Polímeros/química , Sulfóxidos , Propriedades de Superfície
15.
ACS Macro Lett ; 11(10): 1195-1201, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36108166

RESUMO

A major challenge in the preparation of polymeric 19F magnetic resonance imaging (MRI) contrast agents (CAs) is signal attenuation caused by reduced segmental mobility of partly fluorinated polymers possessing large numbers of fluorine atoms. Previous studies have thus mainly focused on the development of fluorinated segments for improved 19F MRI; however, detailed investigations of the role of hydrophilic segments on imaging performance remain scarce. In this study, three hydrophilic and biocompatible monomers, i.e., 2-(methylsulfinyl)ethyl acrylate (MSEA), oligo(ethylene glycol) methyl ether acrylate (OEGA), and oligo(2-methyl-2-oxazoline) acrylate (OMOXA), were used to prepare perfluoropolyether (PFPE)-containing amphiphilic block polymers through reversible addition-fragmentation chain-transfer (RAFT) polymerization. The effect of the different hydrophilic segments on 19F imaging performance was explored. The three polymers could be readily dissolved in aqueous solutions, forming assemblies with the hydrophobic PFPE as the core and the hydrophilic chains as the shell. Molecular dynamics simulations demonstrate that the POMOXA chains adopt a rigid, extended conformation, leading to a relatively short 19F NMR spin-spin relaxation time (T2), lower NMR detectable 19F spins (i.e., visibility), and the least intense 19F MRI signal. In contrast, although PMSEA-PFPE has a shorter 19F NMR T2 than POEGA-PFPE, the much higher 19F spin visibility enhances its MRI signal intensity. The result confirms the importance of maintaining both high fluorine visibility and long T2 relaxation time to prepare effective CAs and highlight the key role of the nonfluorinated hydrophilic segments in determining these parameters.


Assuntos
Meios de Contraste , Éteres Metílicos , Acrilatos , Meios de Contraste/química , Éteres , Etilenoglicóis , Fluoretos , Flúor/química , Polímeros de Fluorcarboneto , Fluorocarbonos , Imageamento por Ressonância Magnética/métodos , Polímeros/química
16.
ACS Appl Mater Interfaces ; 14(36): 41400-41411, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36040859

RESUMO

Antifouling and antibacterial surfaces that can prevent nonspecific biological adhesion are important to support a myriad of biomedical applications. In this study, we have used an innovative photopolymerization technology to develop sulfur-containing polymer-grafted antifouling and antibacterial surfaces. The relationship between the hydrophilic property and the capability to resist protein and macrophage adsorption of the surface copolymer brushes was investigated. The sulfide monomer incorporated into the surface copolymer brushes can be further ionized to carry positive charges and impart antibacterial activity, leading to surfaces with dual antifouling and antibacterial functions. We believe that the reported sulfur-containing polymer brushes can be considered an emerging and important polymer for antifouling and antibacterial applications.


Assuntos
Incrustação Biológica , Adsorção , Antibacterianos/farmacologia , Incrustação Biológica/prevenção & controle , Polímeros/farmacologia , Enxofre , Propriedades de Superfície
17.
Clin Transl Sci ; 15(10): 2493-2504, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35971596

RESUMO

This phase Ib study compared the effects of AZD9977, a selective mineralocorticoid receptor modulator with predicted low hyperkalemia risk, with spironolactone on serum potassium (sK+ ) in patients with heart failure (HF) with preserved or mildly reduced ejection fraction (EF; ≥40%), and renal impairment. Patients with HF with EF greater than or equal to 40% and estimated glomerular filtration rate of 40-70 ml/min/1.73 m2 were randomized to once-daily AZD9977 100 mg or spironolactone 25 mg for 14 days, up-titrated to AZD9977 200 mg or spironolactone 50 mg for another 14 days. The primary end point was relative change (%) in sK+ for AZD9977 versus spironolactone (baseline to day 28). Serum/urinary electrolytes, fractional excretion (FE) of Na+ /K+ , plasma aldosterone, cortisol, and renin, and safety were also assessed. Sixty-eight patients were randomized (AZD9977, n = 33; spironolactone, n = 35). Mean (SD) age was 73.0 (8.5) years, 51.5% men. Mean sK+ change from baseline to day 28 was 5.7% (AZD9977) and 4.2% (spironolactone), and 1.5% and 4.2% at day 14. Relative change (95% confidence interval) in sK+ with AZD9977 versus spironolactone was -0.3% (-5.3% to 4.4%; day 28), and 3.4% (-0.8% to 7.5%; day 14). Median increase from baseline in plasma aldosterone at day 28 was 89.8 pmol/L for AZD9977 and 67.4 pmol/L for spironolactone. Median FE of K+ was 12.9% (AZD9977) and 10.1% (spironolactone). AZD9977 was well-tolerated. No discontinuations due to hyperkalemia occurred with either treatment. Evidence of target engagement for AZD9977 with a favorable safety profile, supports further evaluation of AZD9977 in patients with HF and renal impairment.


Assuntos
Insuficiência Cardíaca , Antagonistas de Receptores de Mineralocorticoides , Espironolactona , Idoso , Feminino , Humanos , Masculino , Aldosterona , Eletrólitos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Hidrocortisona , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/diagnóstico , Hiperpotassemia/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Potássio , Receptores de Mineralocorticoides , Renina , Espironolactona/efeitos adversos , Volume Sistólico , Resultado do Tratamento
18.
Biomacromolecules ; 23(9): 3866-3874, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-35977724

RESUMO

Gold nanorods (GNRs) are widely used in various biomedical applications such as disease imaging and therapy due to their unique plasmonic properties. To improve their bioavailability, GNRs often need to be coated with hydrophilic polymers so as to impart stealth properties. Poly(ethylene glycol) (PEG) has been long used as such a coating material for GNRs. However, there is increasing acknowledgement that the amphiphilic nature of PEG facilitates its interaction with protein molecules, leading to immune recognition and consequent side effects. This has motivated the search for new classes of low-fouling polymers with high hydrophilicity as alternative low-fouling surface coating materials for GNRs. Herein, we report the synthesis, characterization, and application of GNRs coated with highly hydrophilic sulfoxide-containing polymers. We investigated the effect of the sulfoxide polymer coating on the cellular uptake and in vivo circulation time of the GNRs and compared these properties with pegylated GNR counterparts. The photothermal effect and photoacoustic imaging of these polymer-coated GNRs were also explored, and the results show that these GNRs are promising as nanotheranostic particles for the treatment of cancer.


Assuntos
Ouro , Nanotubos , Ouro/farmacologia , Polímeros , Medicina de Precisão , Sulfóxidos
19.
Nat Mater ; 21(9): 1057-1065, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35788569

RESUMO

Rechargeable batteries paired with sodium metal anodes are considered to be one of the most promising high-energy and low-cost energy-storage systems. However, the use of highly reactive sodium metal and the formation of sodium dendrites during battery operation have caused safety concerns, especially when highly flammable liquid electrolytes are used. Here we design and develop solvent-free solid polymer electrolytes (SPEs) based on a perfluoropolyether-terminated polyethylene oxide (PEO)-based block copolymer for safe and stable all-solid-state sodium metal batteries. Compared with traditional PEO SPEs, our results suggest that block copolymer design allows for the formation of self-assembled nanostructures leading to high storage modulus at elevated temperatures with the PEO domains providing transport channels even at high salt concentration (ethylene oxide/sodium = 8/2). Moreover, it is demonstrated that the incorporation of perfluoropolyether segments enhances the Na+ transference number of the electrolyte to 0.46 at 80 °C and enables a stable solid electrolyte interface. The new SPE exhibits highly stable symmetric cell-cycling performance at high current density (0.5 mA cm-2 and 1.0 mAh cm-2, up to 1,000 h). Finally, the assembled all-solid-state sodium metal batteries demonstrate outstanding capacity retention, long-term charge/discharge stability (Coulombic efficiency, 99.91%; >900 cycles with Na3V2(PO4)3 cathode) and good capability with high loading NaFePO4 cathode (>1 mAh cm-2).

20.
Artigo em Inglês | MEDLINE | ID: mdl-35834778

RESUMO

C3-symmetric molecules carrying a conjugated diacetylene (DA) core are found to self-assemble into well-defined supramolecular fibers with enhanced supramolecular chirality in both organic and aqueous solutions. The conjugated core affords these amphiphiles characteristic fluorescence properties, which can be quenched partially due to the aggregation. Integration of the C3-symmetry with the conjugation provides these novel molecules strong aggregation tendency through solvent-mediated π-π stacking with preferential supramolecular chirality, which is predominately related to steric hindrance from their dipeptide pendants. Highly uniform supramolecular fibers of P and M handedness with thickness consistent in the dimensions of individual C3 molecules are obtained. The increase of concentrations induces these fibers to wrap together to form supramolecular fibrous bundles. Topochemical polymerization of the DA moieties can transform these supramolecular fibers into stable covalent polymers. We therefore believe that self-assembly of these C3-symmetric molecules with extended conjugated DA cores provides new prospects for the construction of supramolecular helical fibers through enhanced π-π stacking and creates a convenient strategy to furnish covalent chiral polymers of hierarchical structures through supramolecular assembly.

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