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1.
Adv Healthc Mater ; : e2401708, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38875524

RESUMO

Despite laparoscopic-guided minimally invasive hepatectomy emerging as the primary approach for resecting hepatocellular carcinoma (HCC), there's still a significant gap in suitable biomaterials that seamlessly integrate with these techniques to achieve effective hemostasis and suppress residual tumors at the surgical margin. Electrospun films are increasingly used for wound closure, yet the employment of prefabricated electrospun films for hemostasis during minimally invasive HCC resection is hindered by prolonged operation times, complexity in implementation, limited visibility during surgery, and inadequate postoperative prevention of HCC recurrence. In this study, we integrated montmorillonite-iron oxide sheets into the PVP polymer framework, enhancing the resulting electrospun polyvinylpyrrolidone (PVP) /montmorillonite-iron oxide (MI) film (abbreviated as PMI) with robustness, hemostatic capability, and magnetocaloric properties. In contrast to the in vitro prefabricated electrospun films, the electrospun PMI film is designed to be formed in situ on liver wounds under laparoscopic guidance during hepatectomy. This design affords superior wound adaptability, facilitating meticulous wound closure and expeditious hemostasis, thereby simplifying the operative process and ultimately alleviating the workload of healthcare professionals. Moreover, when exposed to an alternating magnetic field, the film can efficiently ablate residual tumors, significantly augmenting the treatment efficacy of HCC. This article is protected by copyright. All rights reserved.

2.
Adv Mater ; 36(26): e2309770, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38447017

RESUMO

Percutaneous thermotherapy, a minimally invasive operational procedure, is employed in the ablation of deep tumor lesions by means of target-delivering heat. Conventional thermal ablation methods, such as radiofrequency or microwave ablation, to a certain extent, are subjected to extended ablation time as well as biosafety risks of unwanted overheating. Given its effectiveness and safety, percutaneous thermotherapy gains a fresh perspective, thanks to magnetic hyperthermia. In this respect, an injectable- and magnetic-hydrogel-construct-based thermal ablation agent is likely to be a candidate for the aforementioned clinical translation. Adopting a simple and environment-friendly strategy, a magnetic colloidal hydrogel injection is introduced by a binary system comprising super-paramagnetic Fe3O4 nanoparticles and gelatin nanoparticles. The colloidal hydrogel constructs, unlike conventional bulk hydrogel, can be easily extruded through a percutaneous needle and then self-heal in a reversible manner owing to the unique electrostatic cross-linking. The introduction of magnetic building blocks is exhibited with a rapid magnetothermal response to an alternating magnetic field. Such hydrogel injection is capable of generating heat without limitation of deep penetration. The materials achieve outstanding therapeutic results in mouse and rabbit models. These findings constitute a new class of locoregional interventional thermal therapies with minimal collateral damages.


Assuntos
Carcinoma Hepatocelular , Coloides , Hidrogéis , Neoplasias Hepáticas , Animais , Coelhos , Camundongos , Hidrogéis/química , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Coloides/química , Gelatina/química , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Hipertermia Induzida/métodos , Linhagem Celular Tumoral , Injeções , Nanopartículas Magnéticas de Óxido de Ferro/química
3.
Small ; 20(3): e2300733, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37452437

RESUMO

Relapse and unresectability have become the main obstacle for further improving hepatocellular carcinoma (HCC) treatment effect. Currently, single therapy for HCC in clinical practice is limited by postoperative recurrence, intraoperative blood loss and poor patient outcomes. Multidisciplinary therapy has been recognized as the key to improving the long-term survival rate for HCC. However, the clinical application of HCC synthetic therapy is restricted by single functional biomaterials. In this study, a magnetic nanocomposite hydrogel (CG-IM) with iron oxide nanoparticle-loaded mica nanosheets (Iron oxide nanoparticles@Mica, IM) is reported. This biocompatible magnetic hydrogel integrated high injectability, magnetocaloric property, mechanical robustness, wet adhesion, and hemostasis, leading to efficient HCC multidisciplinary therapies including postoperative tumor margin treatment and percutaneous locoregional ablation. After minimally invasive hepatectomy of HCC, the CG-IM hydrogel can facilely seal the bleeding hepatic margin, followed by magnetic hyperthermia ablation to effectively prevent recurrence. In addition, CG-IM hydrogel can inhibit unresectable HCC by magnetic hyperthermia through the percutaneous intervention under ultrasound guidance.


Assuntos
Silicatos de Alumínio , Carcinoma Hepatocelular , Hipertermia Induzida , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Hidrogéis/farmacologia , Fenômenos Magnéticos
4.
Adv Sci (Weinh) ; 10(7): e2204793, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36698293

RESUMO

The passive diffusion performance of nanocarriers results in inefficient drug transport across multiple biological barriers and consequently cancer therapy failure. Here, a magnetically driven amoeba-like nanorobot (amNR) is presented for whole-process active drug transport. The amNR is actively extravasated from blood vessels and penetrated into deep tumor tissue through a magnetically driven deformation effect. Moreover, the acidic microenvironment of deep tumor tissue uncovers the masked targeting ligand of amNR to achieve active tumor cell uptake. Furthermore, the amNR rapidly releases the encapsulated doxorubicin (DOX) after alternating magnetic field application. The amNRs eventually deliver DOX into ≈92.3% of tumor cells and completely delay tumor growth with an inhibition rate of 96.1%. The deformable amNRs, with the assistance of magnetic field application, provide a facile strategy for whole-process active drug transport.


Assuntos
Amoeba , Transporte Biológico , Doxorrubicina , Campos Magnéticos
5.
Nanoscale ; 15(1): 365-375, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36508179

RESUMO

Multifunctional magnet-fluorescent nanocomposites are widely applied in biomedical applications. Incorporating biocompatible quantum dots with highly ferrimagnetic magnetic nanoparticles into one nanoplatform for achieving efficient magnetic hyperthermia therapy (MHT) is very important. Herein, we reported an amphiphilic block copolymer with a flowable hydrophobic chain to encapsulate highly ferrimagnetic magnetic nanoparticles and ZnS/InP quantum dots via a facile self-assembly method. The obtained ferrimagnetic fluorescent micelle (FMFM) exhibited a uniform diameter of about 180 nm. In stark contrast, larger aggregation (400 nm in diameter) inevitably occurred using common poly(D,L-lactide) (PLA)-based amphiphilic block copolymer with a rigid hydrophobic chain, which was readily cleared by the reticuloendothelial system (RES). The flowable FMFM exhibited long-term colloidal stability within one month and desired fluorescent stability within 84 h. Benefiting from the high ferrimagnetism, the FMFM revealed excellent magnetic heating effect and magnetic resonance imaging capability. With accurate manipulation under an external magnetic field, FMFM realized in vitro enhanced fluorescence imaging sensitivity and accumulation efficiency at the tumor region, achieving in vitro and vivo improved MHT efficacy.


Assuntos
Hipertermia Induzida , Nanopartículas , Pontos Quânticos , Micelas , Polímeros/química
6.
J Nanobiotechnology ; 20(1): 381, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35986283

RESUMO

Bioactive materials have been extensively developed for the adjuvant therapy of cancer. However, few materials can meet the requirements for the postoperative resection of hepatocellular carcinoma (HCC) due to massive bleeding and high recurrence. In particular, combination therapy for HCC has been highly recommended in clinical practice, including surgical resection, interventional therapy, ablation therapy and chemotherapy. Herein, an injectable magnetic colloidal gel (MCG) was developed by controllable electrostatic attraction between clinically available magnetic montmorillonites and amphoteric gelatin nanoparticles. The optimized MCG exhibited an effective magnetic heating effect, remarkable rheological properties, and high gel network stability, realizing the synergistic treatment of postoperative HCC by stimuli-responsive drug delivery, hemostasis and magnetic hyperthermia. Furthermore, a minimal invasive MCG-induced interventional magnetic hyperthermia therapy (MHT) under ultrasound guidance was realized on hepatic tumor rabbits, providing an alternative therapeutics to treat the postoperative recurrence. Overall, MCG is a clinically available injectable formulation for adjuvant therapy after HCC surgical resection.


Assuntos
Carcinoma Hepatocelular , Hipertermia Induzida , Neoplasias Hepáticas , Animais , Bentonita/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Fenômenos Magnéticos , Coelhos
7.
ACS Nano ; 16(9): 15226-15236, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36018240

RESUMO

In situ cancer vaccines consisting of antigens and adjuvants are a promising cancer treatment modality; however, the convenient manufacture of vaccines in vivo and their efficient delivery to lymph nodes (LNs) remains a major challenge. Herein, we outline a facile approach to simultaneously achieve the in situ programming of vaccines via two synergetic nanomedicines, Tu-NPFN and Ln-NPR848. Tu-NPFN (∼100 nm) generated a large number of antigens under an alternating magnetic field, and Ln-NPR848 (∼35 nm) encapsulating adjuvant R848 captured a portion of generated antigens for the manufacture of nanovaccines in situ and LN-targeted delivery, which significantly promoted the uptake and maturation of dendritic cells to initiate potent anticancer immune responses. Notably, combined with an anti-CTLA4 antibody (aCTLA-4), this therapy completely eradicated distant tumors in some mice and exerted a long-term immune memory effect on tumor metastasis. This study provides a generalizable strategy for in situ cancer vaccination.


Assuntos
Vacinas Anticâncer , Neoplasias , Adjuvantes Imunológicos , Animais , Antígenos , Imunoterapia , Linfonodos , Camundongos , Neoplasias/patologia
8.
Nano Lett ; 22(6): 2251-2260, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35254836

RESUMO

Current surgical single modality treatments for hepatocellular carcinoma (HCC) were restricted by recurrence, blood loss, significant trauma, and poor prognostic. Although multidisciplinary strategies for HCC treatment have been highly recommended by the clinical guidelines, there was limited choice of materials and treatments. Herein, we reported an in situ formed magnetic hydrogel with promising bioapplicable thermal-responsiveness, strong adhesion in wet conditions, high magnetic hyperthermia, and biocompatibility, leading to efficient HCC multidisciplinary treatment including postoperative treatment and transarterial embolization therapy. In vivo results indicated that this hydrogel could reduce the postoperative recurrence rate. The hemostatic ability of the thermal-responsive hydrogel was further demonstrated in both the liver scratch model and liver tumor resection. Computed tomography imaging suggested that the hydrogel could completely embolize the arterial vessels of rabbit liver tumor by vascular intervention operation, which could serve as multidisciplinary responsive materials to external magnetic field and body temperature for HCC treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Hepatectomia/métodos , Hidrogéis/uso terapêutico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Fenômenos Magnéticos , Coelhos
9.
Adv Mater ; 33(36): e2100074, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34297448

RESUMO

The high viscosity and low fluidity of heavy crude oil hinder its sorption by conventional porous sorbents, so the efficient clean-up of such heavy crude oil spills is challenging. Recently, Joule heating has been emerging as a new tool to reduce the viscosity of heavy crude oil dramatically. However, this direct-contact heating approach presents a potential risk due to the high voltage applied. To develop a non-contact recovery of viscous crude oil, here, a new approach for the fabrication of a series of ferrimagnetic sponges (FMSs) with hydrophobic porous channels is reported, whose surface can be remotely heated to 120 °C within 10 s under an alternating magnetic field (f = 274 kHz, H = 30 kA m-1 ). Compared with the solar-driven superficial heating, the integral magnetic heating in FMSs can result in a higher internal temperature of the sponges because of the confinement of thermal transport in the porous channels, which contributes to a dramatic decrease in oil viscosity and a significant increase in oil flow into the pores of FMSs. Furthermore, FMSs assembled with a self-priming pump can achieve continuous recovery of viscous crude oil (33.05 g h-1 cm-2 ) via remotely magnetic heating.

10.
Nat Commun ; 12(1): 2305, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863884

RESUMO

The selective hydrogenation of CO2 to value-added chemicals is attractive but still challenged by the high-performance catalyst. In this work, we report that gallium nitride (GaN) catalyzes the direct hydrogenation of CO2 to dimethyl ether (DME) with a CO-free selectivity of about 80%. The activity of GaN for the hydrogenation of CO2 is much higher than that for the hydrogenation of CO although the product distribution is very similar. The steady-state and transient experimental results, spectroscopic studies, and density functional theory calculations rigorously reveal that DME is produced as the primary product via the methyl and formate intermediates, which are formed over different planes of GaN with similar activation energies. This essentially differs from the traditional DME synthesis via the methanol intermediate over a hybrid catalyst. The present work offers a different catalyst capable of the direct hydrogenation of CO2 to DME and thus enriches the chemistry for CO2 transformations.

11.
Biomaterials ; 259: 120299, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32827797

RESUMO

Due to the well-recognized biocompatibility, silk fibroin hydrogels have been developed for biomedical applications including bone regeneration, drug delivery and cancer therapy. For the treatment of cancer, silk-based photothermal agents exhibit the high photothermal conversion efficiency, but the limited light penetration depth of photothermal therapy restricts the treatment of some tumors in deep positions, such as liver tumor and glioma. To provide an alternative strategy, here we developed an injectable magnetic hydrogel based on silk fibroin and iron oxide nanocubes (IONCs). The as-prepared ferrimagnetic silk fibroin hydrogel could be easily injected through a syringe into tumor, especially rabbit hepatocellular carcinoma in deeper positions using ultrasound-guided interventional treatment. Compared with photothermal agents, the embedded IONCs endowed the ferrimagnetic silk fibroin hydrogel with remote hyperthermia performance under an alternating magnetic field, resulting in the effective magnetic hyperthermia of deep tumors including subcutaneously implanted tumor model in Balb/c mouse after the coverage of a fresh pork tissue and orthotopic transplantation liver tumor in rabbit. Furthermore, due to the confinement of IONCs in silk fibroin hydrogel, the undesired thermal damage toward normal tissue could be avoided compared with directly administrating monodispersed magnetic nanoparticles.


Assuntos
Fibroínas , Neoplasias , Animais , Hidrogéis , Hipertermia , Fenômenos Magnéticos , Camundongos , Coelhos , Seda
12.
Natl Sci Rev ; 7(4): 723-736, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34692091

RESUMO

As a non-invasive therapeutic method without penetration-depth limitation, magnetic hyperthermia therapy (MHT) under alternating magnetic field (AMF) is a clinically promising thermal therapy. However, the poor heating conversion efficiency and lack of stimulus-response obstruct the clinical application of magnetofluid-mediated MHT. Here, we develop a ferrimagnetic polyethylene glycol-poly(2-hexoxy-2-oxo-1,3,2-dioxaphospholane) (mPEG-b-PHEP) copolymer micelle loaded with hydrophobic iron oxide nanocubes and emodin (denoted as EMM). Besides an enhanced magnetic resonance (MR) contrast ability (r 2 = 271 mM-1 s-1) due to the high magnetization, the specific absorption rate (2518 W/g at 35 kA/m) and intrinsic loss power (6.5 nHm2/kg) of EMM are dozens of times higher than the clinically available iron oxide nanoagents (Feridex and Resovist), indicating the high heating conversion efficiency. Furthermore, this composite micelle with a flowable core exhibits a rapid response to magnetic hyperthermia, leading to an AMF-activated supersensitive drug release. With the high magnetic response, thermal sensitivity and magnetic targeting, this supersensitive ferrimagnetic nanocomposite realizes an above 70% tumor cell killing effect at an extremely low dosage (10 µg Fe/mL), and the tumors on mice are completely eliminated after the combined MHT-chemotherapy.

13.
ACS Nano ; 13(9): 10074-10084, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31430428

RESUMO

An in situ forming hydrogel has emerged as a promising wound dressing recently. As physically cross-linked hydrogels are normally unstable, most in situ forming hydrogels are chemically cross-linked. However, big concerns have remained regarding the slow gelation and the potential toxicity of residual functional groups from cross-linkers or the polymer matrix. Herein, we report a sprayable in situ forming hydrogel composed of poly(N-isopropylacrylamide166-co-n-butyl acrylate9)-poly(ethylene glycol)-poly(N-isopropylacrylamide166-co-n-butyl acrylate9) copolymer (P(NIPAM166-co-nBA9)-PEG-P(NIPAM166-co-nBA9), denoted as PEP) and silver-nanoparticles-decorated reduced graphene oxide nanosheets (Ag@rGO, denoted as AG) in response to skin temperature. This thermoresponsive hydrogel exhibits intriguing sol-gel irreversibility at low temperatures for the stable dressing of a wound, which is attributed to the inorganic/polymeric dual network and abundant coordination interactions between Ag@rGO nanosheets and PNIPAM. The biocompatibility and antibacterial ability against methicillin-resistant Staphylococcus aureus (MRSA) of this PEP-AG hydrogel wound dressing are confirmed in vitro and in vivo, which could transparently promote the healing of a MRSA-infected skin defect.


Assuntos
Hidrogéis/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Transição de Fase , Temperatura , Cicatrização/efeitos dos fármacos , Resinas Acrílicas/síntese química , Resinas Acrílicas/química , Animais , Bandagens , Materiais Biocompatíveis/farmacologia , Grafite/química , Hidrogéis/síntese química , Hidrogéis/química , Testes de Sensibilidade Microbiana , Oxirredução , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/microbiologia , Pele/patologia
14.
Biomater Sci ; 7(3): 867-875, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30648710

RESUMO

As an active natural ingredient extracted from the plant Rheum palmatum, emodin exhibits various pharmacological activities, especially the inhibition of tumor growth and migration. However, the anticancer activity of emodin is limited mainly due to its poor solubility and the lack of specific targeting. Herein, we employed liposome to load emodin into the lipid bilayer, and high-performance ferromagnetic iron oxide nanocubes were simultaneously encapsulated in the hydrophilic bilayer. The optimized magnetic liposomal emodin nanocomposite (MLE) exhibited a 24.1% increase in the efficiency of killing MCF-7 cancer cells at a low concentration of 16 µg mL-1 compared with that of the hydrophobic free emodin. A further 8.67% enhancement of the killing efficiency was obtained by magnetic targeting. Benefitting from the high ferromagnetism, the transverse relaxivity (r2) of MLE was measured to be as high as 392.9 mM-1 s-1. With guidance from the external magnetic field, the effective accumulation of this magnetic liposome in the tumor region of a 4T1 breast tumor bearing mouse was observed by both MR tracking and fluorescence imaging, which should be beneficial for decreasing the required therapeutic dose of emodin. Hemolysis, cytotoxicity and biochemistry assays confirmed the excellent biocompatibility of this magnetic liposomal carrier. The anti-tumor therapeutic effect of MLE was further investigated in vivo, and the tumor in the therapeutic group was almost eliminated, indicating that this magnetic liposomal emodin could serve as a novel magnetically guided theranostic nanoagent.


Assuntos
Emodina/química , Lipossomos/química , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Emodina/uso terapêutico , Emodina/toxicidade , Feminino , Compostos Férricos/química , Hemólise/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células MCF-7 , Imageamento por Ressonância Magnética , Magnetismo , Camundongos , Camundongos Endogâmicos BALB C , Nanocompostos/química , Nanocompostos/toxicidade , Transplante Heterólogo
15.
J Liposome Res ; 29(2): 133-141, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30022692

RESUMO

The purpose of this study was to optimize the preparation conditions of podophyllotoxin liposomes (PPT-Lips), and to investigate their effects on PC3 cells. PPT-Lips were prepared by using a thin-film dispersion method. In order to achieve maximum drug encapsulation efficiency (EE), the process and formulation variables were optimized by response surface methodology (RSM). The optimum preparation conditions were cholesterol to lecithin ratio of 3.6:40 (w/w), lipid to drug ratio of 15.8:1 (w/w), and the ultrasonic intensity of 35% (total power of 400 W). The experimental EE of PPT-Lips was 90.425%, which was consistent with the theoretically predicted value. The characterization studies showed that PPT-Lips were well-dispersible spherical particles with an average size of 106 nm and a zeta potential of -10.1 mV. A gradual and time-dependent pattern of PPT from liposomes was found in in vitro drug release with a cumulative release amount up to 70.3% in 24 h. Results of cell viability experiments on PC3 cells demonstrated that PPT-Lips exhibited more effective anticancer activity in comparison with free PPT. Therefore, PPT-Lips represent an efficient and promising drug delivery system for PPT.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Lipossomos/química , Nanopartículas/química , Podofilotoxina/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Colesterol/química , Cromatografia Líquida de Alta Pressão , Liberação Controlada de Fármacos , Humanos , Lecitinas/química , Masculino , Células PC-3 , Podofilotoxina/administração & dosagem
16.
ACS Appl Mater Interfaces ; 10(37): 31044-31053, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30148600

RESUMO

As a pharmaceutical excipient, dextran serves as an efficient ligand for stabilizing some clinically available inorganic nanomaterials such as iron oxide nanocrystals. Herein, dextran-capped nanosized europium(III) hydroxides [Eu(OH)3] nanoclusters (NCs) composed of 5 nm Eu(OH)3 nanoparticles have been large-scale synthesized via a microwave-accelerated hydrothermal reaction. The as-synthesized Eu(OH)3 NCs exhibited excellent physiological stability and biocompatibility both in vitro and in vivo and possessed considerable pro-proliferative activities in human umbilical vein endothelial cells (HUVECs). To investigate the epigenetic modulation of Eu(OH)3 NCs-elicited proliferation, the newly developed high-throughput next generation sequencing technology was employed herein. As a result, we have screened 371 dysregulated miRNAs in Eu(OH)3 NCs-treated HUVECs and obtained 26 potentially functional miRNAs in promoting cell proliferation. Furthermore, upregulated miR-199a-3p was predicted, validated, and eventually confirmed to be a crucial modulator in the pro-proliferative activity of Eu(OH)3 NCs by targeting zinc fingers and homeoboxes protein 1 (ZHX1). Importantly, these findings provide potential therapeutic strategy for ischemic heart/limb diseases and tissue regeneration by combination of nanomedicine and gene therapy with Eu(OH)3 NCs and miR-199a-3p-ZHX1 axis modulation.


Assuntos
MicroRNAs/metabolismo , Micro-Ondas , Nanopartículas/química , Proliferação de Células/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos
17.
PeerJ ; 6: e5369, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30065898

RESUMO

Cecropins, originally found in insects, are a group of cationic antimicrobial peptides. Most cecropins have an amphipathic N-terminal segment and a largely hydrophobic C-terminal segment, and normally form a helix-hinge-helix structure. In this study, we developed the novel 32-residue cecropin-like peptide cecropin DH by deleting the hinge region (Alanine-Glycine-Proline) of cecropin B isolated from Chinese oak silk moth, Antheraea pernyi. Cecropin DH possesses effective antibacterial activity, particularly against Gram-negative bacteria, with very low cytotoxicity against mammalian cells. Interactions between cecropin DH and the highly anionic lipopolysaccharide (LPS) component of the Gram-negative bacterial outer membrane indicate that it is capable of dissociating LPS micelles and disrupting LPS aggregates into smaller assemblies, which may play a vital role in its antimicrobial activity. Using LPS-stimulated mouse macrophage RAW264.7 cells, we found that cecropin DH exerted higher potential anti-inflammatory activity than cecropin B, as demonstrated by the inhibition of pro-inflammatory cytokines nitric oxide production and secretion of tumor necrosis factor-α. In conclusion, cecropin DH has potential as a therapeutic agent for both antibacterial and anti-inflammatory applications.

18.
Biomater Sci ; 5(12): 2403-2415, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29072715

RESUMO

It is a significant challenge to develop nanoscale magnetic resonance imaging (MRI) contrast agents with high performance of relaxation. In this work, Gd3+-doped CaF2-based core-shell nanoparticles (CaF2:Yb,Er@CaF2:Gd) of sub-10 nm size were controllably synthesized by a facile sequential growth method. The as-prepared hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles modified using PEG-PAA di-block copolymer benefited from the presence of Gd only in the outer CaF2 layer of the nanoparticles, which exhibited r1 as high as 21.86 mM-1 s-1 under 3.0 T, seven times as high as that of commercially used gadopentetate dimeglumine (Gd-DTPA). Low cytotoxicity, no hemolysis phenomenon and no potential gadolinium ion leakage phenomenon of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles have been observed and confirmed. Clear vascular details can be observed in magnetic resonance angiography and obvious MR signal of 4T1 tumor area could be significantly improved by intravenous injection of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles at a low dosage in mice. A series of in vivo biological safety evaluations confirmed the good biocompatibility of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles, which might be employed in clinical blood pool imaging and tumor diagnosis as a safe and efficient MRI probe.


Assuntos
Angiografia por Ressonância Magnética/métodos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/diagnóstico , Animais , Meios de Contraste/química , Meios de Contraste/uso terapêutico , Gadolínio/química , Gadolínio/uso terapêutico , Células HeLa , Humanos , Imageamento por Ressonância Magnética/métodos , Camundongos , Nanopartículas/uso terapêutico , Neoplasias/patologia , Itérbio/química , Itérbio/uso terapêutico
19.
J Biol Chem ; 292(40): 16571-16577, 2017 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-28808052

RESUMO

Mavacamten, formerly known as MYK-461 is a recently discovered novel small-molecule modulator of cardiac myosin that targets the underlying sarcomere hypercontractility of hypertrophic cardiomyopathy, one of the most prevalent heritable cardiovascular disorders. Studies on isolated cells and muscle fibers as well as intact animals have shown that mavacamten inhibits sarcomere force production, thereby reducing cardiac contractility. Initial mechanistic studies have suggested that mavacamten primarily reduces the steady-state ATPase activity by inhibiting the rate of phosphate release of ß-cardiac myosin-S1, but the molecular mechanism of action of mavacamten has not been described. Here we used steady-state and presteady-state kinetic analyses to investigate the mechanism of action of mavacamten. Transient kinetic analyses revealed that mavacamten modulates multiple steps of the myosin chemomechanical cycle. In addition to decreasing the rate-limiting step of the cycle (phosphate release), mavacamten reduced the number of myosin-S1 heads that can interact with the actin thin filament during transition from the weakly to the strongly bound state without affecting the intrinsic rate. Mavacamten also decreased the rate of myosin binding to actin in the ADP-bound state and the ADP-release rate from myosin-S1 alone. We, therefore, conclude that mavacamten acts on multiple stages of the myosin chemomechanical cycle. Although the primary mechanism of mavacamten-mediated inhibition of cardiac myosin is the decrease of phosphate release from ß-cardiac myosin-S1, a secondary mechanism decreases the number of actin-binding heads transitioning from the weakly to the strongly bound state, which occurs before phosphate release and may provide an additional method to modulate myosin function.


Assuntos
Difosfato de Adenosina/química , Trifosfato de Adenosina/química , Benzilaminas/química , Miosinas Cardíacas/química , Subfragmentos de Miosina/química , Sarcômeros/química , Uracila/análogos & derivados , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Miosinas Cardíacas/metabolismo , Cardiomegalia/metabolismo , Bovinos , Subfragmentos de Miosina/metabolismo , Sarcômeros/metabolismo , Uracila/química
20.
J Biomed Nanotechnol ; 13(11): 1435-1445, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271130

RESUMO

As a phenyltetralin-type lignin isolated from roots and rhizomes of Podophyllum hexandrum, podophyllotoxin (POD) possesses a great deal of biological activities, especially the anticancer activity via preventing the division of cancerous cells. However, its practical clinical application as an anticancer agent is hindered by its poor water solubility and serious side effects. Herein, we enclosed the POD into the hydrophobic cavity of natural phosphatidylcholine based liposomes to improve its solubility and thus, enhance the chemotherapeutic effect. Modified gold nanorods (GNRs) were further conjugated onto the liposomal POD composite (GLP) for enhanced photothermal stability. The extinction coefficient of GLP aqueous dispersion at 808 nm was calculated to be 8.08 Lg-1 cm-1, and the photothermal conversion efficiency was calculated to be 46.1%. In addition, the release of POD from GLP composite was effectively triggered by NIR irradiation. Compared with the cellular viabilities in the single chemotherapy group (54.6%) and the single photothermal therapy group (66.9%), only 10.3% 4T1 cells were survived after photothermal and chemotherapy simultaneously in the GLP group after exposure to 808 nm NIR laser at an intensity of 1.0 W/cm² for 5 min. The cytotoxicity and hemolysis assay further demonstrated the excellent biocompatibility of POD based liposomal composite. Overall, the GNRs conjugated liposomal POD is a promising therapeutic nanoagent for synergistic chemo-thermal therapy.

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