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1.
ACS Nano ; 18(11): 7972-7988, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38445578

RESUMO

RNA nanotechnology, including rolling circle transcription (RCT), has gained increasing interest as a fascinating siRNA delivery nanoplatform for biostable and tumor-targetable RNA-based therapies. However, due to the lack of fine-tuning technologies for RNA nanostructures, the relationship between physicochemical properties and siRNA efficacy of polymeric siRNA nanoparticles (PRNs) with different sizes has not yet been fully elucidated. Herein, we scrutinized the effects of size/surface chemistry-tuned PRNs on the biological and physiological interactions with tumors. PRNs with adjusted size and surface properties were prepared using sequential engineering processes: RCT, condensation, and nanolayer deposition of functional biopolymers. Through the RCT process, nanoparticles of three sizes with a diameter of 50-200 nm were fabricated and terminated with three types of biopolymers: poly-l-lysine (PLL), poly-l-glutamate (PLG), and hyaluronic acid (HA) for different surface properties. Among the PRNs, HA-layered nanoparticles with a diameter of ∼200 nm exhibited the most effective systemic delivery, resulting in superior anticancer effects in an orthotopic breast tumor model due to the CD44 receptor targeting and optimized nanosized structure. Depending on the type of PRNs, the in vivo siRNA delivery with protein expression inhibition differed by up to approximately 20-fold. These findings indicate that the types of layered biopolymers and the PRNs size mediate efficient polymeric siRNA delivery to the targeted tumors, resulting in high RNAi-induced therapeutic efficacy. This RNA-nanotechnology-based size/surface editing can overcome the limitations of siRNA therapeutics and represents a potent built-in module method to design RNA therapeutics tailored for targeted cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Distribuição Tecidual , Linhagem Celular Tumoral , RNA Interferente Pequeno/genética , Nanopartículas/química , Polímeros/metabolismo , Biopolímeros/metabolismo , Neoplasias/tratamento farmacológico
2.
J Microbiol Biotechnol ; 34(4): 940-948, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38314445

RESUMO

Codium fragile has been traditionally used in oriental medicine to treat enterobiasis, dropsy, and dysuria, and it has been shown to possess many biological properties. Atopic dermatitis (AD) is one of the types of skin inflammation and barrier disruption, which leads to chronic inflammatory skin diseases. In the current investigation, the protective effects of C. fragile extract (CFE) on anti-inflammation and skin barrier improvement were investigated. In LPS-stimulated RAW 264.7 cells, nitric oxide generation and the expression levels of interleukin (IL)-1ß, IL-4, IL-6, iNOS, COX-2, and tumor necrosis factor-alpha (TNF)-α were reduced by CFE. CFE also inhibited the phosphorylation of NF-κB-p65, ERK, p-38, and JNK. Additionally, CFE showed inhibitory activity on TSLP and IL-4 expression in HaCaT cells stimulated with TNF-α/interferon-gamma (IFN-γ). Enhanced expression of factors related to skin barrier function, FLG, IVL, and LOR, was confirmed. These findings implied that CFE may be used as a therapeutic agent against AD due to its skin barrier-strengthening and anti-inflammatory activities, which are derived from natural marine products.


Assuntos
Anti-Inflamatórios , Citocinas , Dermatite Atópica , Proteínas Filagrinas , Queratinócitos , Macrófagos , Óxido Nítrico , Dermatite Atópica/tratamento farmacológico , Humanos , Camundongos , Animais , Anti-Inflamatórios/farmacologia , Queratinócitos/efeitos dos fármacos , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Citocinas/metabolismo , Óxido Nítrico/metabolismo , Pele/efeitos dos fármacos , Células HaCaT , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Lipopolissacarídeos/farmacologia , Linhagem Celular , NF-kappa B/metabolismo , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/genética
3.
Data Brief ; 52: 110002, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38226039

RESUMO

Pistacia chinensis and Pistacia weinmannifolia are small trees and are distributed in East Asia, in particular China. The data on P. chinensis presented in this article is associated with the research article, "DOI: 10.5010/JPB.2019.46.4.274" [1]. Both P. chinensis and P. weinmannifolia have long been used as ethnobotanical plants to treat various illnesses, including dysentery, inflammatory swelling, rheumatism, liver diseases, influenza, lung cancer, etc. Many studies have been carried out to delve into the pharmaceutical properties of these Pistacia species using plant extracts, but genomic studies are very rarely performed to date. To enrich the genetic information of these two species, RNA sequencing was conducted using a pair-end Illumina HiSeq2500 sequencing system, resulting in 2.6 G of raw data from P. chinensis (Accession no: SRR10136265) and 2.7 G bases from P. weinmannifolia (Accession no: SRR10136264). Transcriptome shotgun assembly using three different assembly tools generated a total of 18,524 non-redundant contigs (N50, 1104 bp) from P. chinensis and 18,956 from P. weinmannifolia (N50, 1137 bp). The data is accessible at NCBI BioProject: PRJNA566127. These data would be crucial for the identification of genes associated with the compounds exerting pharmaceutical properties and also for molecular marker development.

4.
Cancer Res Treat ; 56(1): 208-218, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37402409

RESUMO

PURPOSE: BVAC-B is an autologous B cell- and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer. MATERIALS AND METHODS: Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×107 cells/dose), medium (5.0×107 cells/dose), or high dose (1.0×108 cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses. RESULTS: Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients. CONCLUSION: BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy.


Assuntos
Neoplasias Gástricas , Vacinas , Humanos , Trastuzumab/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Monócitos/patologia , Vacinas/uso terapêutico , Imunoterapia
5.
J Control Release ; 365: 422-434, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37863357

RESUMO

A bioactive compound, collagen peptide (CP), is widely used for biological activities such as anti-photoaging and antioxidant effects, with increased oral bioavailability because of its low molecular weight and high hydrophilicity. However, controlling release time and increasing retention time in the digestive tract for a more convenient oral administration is still a challenge. We developed CP-loaded chitosan (CS) microcapsules via strong and rapid ionic gelation using a highly negative phytic acid (PA) crosslinker. The platform enhanced the oral bioavailability of CP with controlled gastrointestinal delivery by utilizing the mucoadhesiveness and tight junction-opening properties of CS. CS and CP concentrations varied from 1.5 to 3.5% and 0-30%, respectively, for optimal and stable microcapsule synthesis. The physicochemical properties, in vitro release profile with intestinal permeability, in vivo oral bioavailability, in vivo biodistribution, anti-photoaging effect, and antioxidant effect of optimized CS microcapsules were analyzed to investigate the impact of controlling parameters. The structure of CS microcapsules was tuned by PA diffused gradient ionic cross-linking degree, resulting in a controlled CP release region in the gastrointestinal tract. The optimized microcapsules increased Cmax, AUC, and tmax by 1.5-, 3.4-, and 8.0-fold, respectively. Furthermore, CP in microcapsules showed anti-photoaging effects by downregulating matrix metalloproteinases-1 via antioxidant effects. According to our knowledge, this is the first study to microencapsulate CP for oral bioavailability enhancement. The peptide delivery method employed is simple, economical, and can be applied to customize bioactive compound administration.


Assuntos
Quitosana , Cápsulas/química , Quitosana/química , Disponibilidade Biológica , Antioxidantes , Peso Molecular , Distribuição Tecidual , Trato Gastrointestinal , Peptídeos , Administração Oral , Portadores de Fármacos/química
6.
Comput Biol Chem ; 106: 107933, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37536229

RESUMO

This study aims to investigate the potential therapeutic application of Ixeridium dentatum (ID) in treating atopic dermatitis (AD) through network pharmacology, molecular docking, and molecular dynamic simulation. We employed GC-MS techniques and identified 40 bioactive compounds present in the ID and determined their targets by accessing public databases. The convergence of compounds and dermatitis related targets led to the identification of 32 common genes. Among them, IL1B, PTGS2, IL6, IL2, and RELA, were found to be significant targets which were analyzed using Cytoscape network topology. The KEGG pathway evaluation revealed that these targets were significantly enriched in the C-type lectin receptor signaling pathway. The therapeutic efficacy of Stigmasta-5,22-dien-3-ol, Urea, n-Heptyl-, and 3-Epimoretenol was demonstrated in molecular docking assay, as evidenced by their presence in the core compounds of the compound-target network. Furthermore, these compounds exhibited significant kinetic stability and chemical reactivity in DFT quantum analysis when compared to their co-crystallized ligands and reference drug, indicating their potential as key targets for future research. Among the top three docking complexes, namely IL6-3-Epimoretenol, and IL2- Stigmasta-5,22-dien-3-ol, both demonstrated exceptional dynamic characteristics in molecular dynamics simulations at 100 ns. The feasibility of these compounds could be attributed to the prior traditional interrelationship between ID and AD. Overall, this research elucidates the interplay between AD-associated signaling pathways and target receptors with the bioactive ID. The proposal posits the utilization of antecedent compounds as a substitute for the customary pharmaceutical intervention that obstructs the discharge of cytokines, which incite dermal inflammation in the C-type lectin receptor signaling pathway of atopic dermatitis.


Assuntos
Dermatite Atópica , Medicamentos de Ervas Chinesas , Humanos , Dermatite Atópica/tratamento farmacológico , Interleucina-2 , Interleucina-6 , Simulação de Acoplamento Molecular , Lectinas Tipo C
7.
J Control Release ; 355: 7-17, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36706839

RESUMO

Despite the vast interest in utilizing rolling circle amplification (RCA)-based DNA networks for bioapplications, precise control of the mechanical and physicochemical properties is highly challenging. To address this concern, we aimed to develop ultrasoft self-supporting polymerized DNA networks (pDNets) of variable crystallinities to manipulate sequence-mediated drug release efficiency. A controlled ratio of the inorganic magnesium pyrophosphate (MgPPi) crystal to the organic polymeric DNA resulted in the synthesis of pDNets of various nanoporosities. The number of crystal microstructures influencing drug localization and release pattern and the tunable mechanical properties influencing injectability and structural stability under physiological conditions were investigated. The pDNets exhibited ultrasoft properties with Young's moduli of 0.06-0.54 Pa; approximately 9-fold differences in mechanical properties were obtained by varying the degree of crystallinity. With functional DNA sequences, the developed platforms showed pH stimuli-responsive drug release profiles of the dynamic DNA structures and aptamer-specific cell target adhesion efficiency. Analyses of controlled delivery of anticancer therapeutics in vitro and in vivo revealed crystallinity-dependent antitumor efficacy without side effects. This strategy provides an effective one-pot enzymatic polymerization methodology and a favorable microenvironment for a three-dimensional DNA network based on demand-localized drug delivery.


Assuntos
Antineoplásicos , DNA , Preparações de Ação Retardada , DNA/química , Sistemas de Liberação de Medicamentos , Oligonucleotídeos , Hidrogéis/química
8.
Bioact Mater ; 22: 365-383, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36311046

RESUMO

Plant-derived vesicles (PDVs) are membranous structures that originate from plant cells and are responsible for multiple physiological and pathological functions. In the last decade, PDVs have gained much attention for their involvement in different biological processes, including intercellular communication and defense response, and recent scientific evidence has opened a new avenue for their applications in cancer treatment. Nevertheless, much remains unknown about these vesicles, and current research remains inconsistent. This review aims to provide a comprehensive introduction to PDVs, from their biological characteristics to purification methods, and to summarize the status of their potential development for cancer therapy.

9.
Biomacromolecules ; 23(6): 2255-2263, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35362323

RESUMO

To date, the application of RNA therapeutics to hematologic malignancies has been challenging owing to the resistance of blood cancer cells against conventional transfection methods. Herein, triple-targeting moiety-functionalized polymeric small interfering RNA (siRNA) nanoparticles were systematically developed for efficient targeted delivery of RNA therapeutics to hematologic cancer cells. Polymeric siRNAs were synthesized using rolling circle transcription and were surface-functionalized with three types of targeting moieties─a natural ligand and two additional combinations of cell-specific antibodies─for tunable targetability. As a proof of concept, the optimization of the hyaluronic acid/antibody conjugation ratio was performed for selective intracellular delivery to various non-Hodgkin's lymphoma (NHL) cell lines (Daudi, Raji, Ramos, and Toledo cells) via receptor-mediated endocytosis. The engineered nanoparticles showed almost 10-fold enhanced NHL-specific intracellular delivery and induced significant in vitro anticancer effects. This multitargeted nanoparticle platform may effectively support the intracellular delivery of polymeric siRNA sequences, and thus promote therapeutic effects in hematopoietic malignancies.


Assuntos
Neoplasias Hematológicas , Nanopartículas , Linhagem Celular Tumoral , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Polímeros , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transfecção
10.
Biomedicines ; 9(3)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809691

RESUMO

Photothermal therapy (PTT) has attracted extensive research attention as a noninvasive and selective treatment strategy for numerous cancers. PTT functions via photothermal effects induced by converting light energy into heat on near-infrared laser irradiation. Despite the great advances in PTT for cancer treatment, the photothermal therapeutics using laser devise only or non-specific small molecule PTT agents has been limited because of its low photothermal conversion efficiency, concerns about the biosafety of the photothermal agents, their low tumor accumulation, and a heat resistance of specific types of cancer. Using nanomaterials as PTT agents themselves, or for delivery of PTT agents, offers improved therapeutic outcomes with fewer side effects through enhanced photothermal conversion efficiency, accumulation of the PTT agent in the tumor tissue, and, by extension, through combination with other therapies. Herein, we review PTT's current clinical progress and present the future outlooks for clinical applications. To better understand clinical PTT applications, we describe nanomaterial-mediated photothermal effects and their mechanism of action in the tumor microenvironment. This review also summarizes recent studies of PTT alone or in combination with other therapies. Overall, innovative and strategically designed PTT platforms are promising next-generation noninvasive cancer treatments to move closer toward clinical applications.

11.
Chem Commun (Camb) ; 56(49): 6624-6627, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32463029

RESUMO

A new dual-targeting polymeric siRNA nanoparticle (Dual-PSNP) was developed via multiple processes: rolling circle transcription, condensation, electrostatic deposition, and click chemistry. The Dual-PSNP showed significantly improved cancer-specific intracellular delivery, gene knockdown efficacy, and apoptosis-mediated cytotoxicity through additive receptor-mediated interactions of the two ligands.


Assuntos
Técnicas de Transferência de Genes , Nanopartículas/química , Neoplasias Ovarianas/tratamento farmacológico , Polímeros/química , RNA Interferente Pequeno/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Terapia Genética , Humanos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética
12.
J Control Release ; 320: 328-336, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-31981658

RESUMO

Liver fibrosis is an excessive wound healing process that occurs in response to liver damage depending on underlying aetiologies. Currently, there are no effective therapies and FDA-approved therapeutics for the treatment of liver fibrosis except liver transplantation. Multipotent adipose-derived stem cells (ADSCs) have received significant attention as regenerative medicine for liver fibrosis owing to their advantages over stem cells with other origins. However, intrinsic limitations of stem cell therapies, such as cellular rejection and tumor formation, have impeded clinical applications of the ADSC-based liver therapeutics. To overcome these problems, the extracellular nanovesicles (ENVs) responsible for the therapeutic effect of ADSCs (A-ENVs) have shown considerable promise as cell-free therapeutics for liver diseases. However, A-ENVs have not been used for the treatment of intractable chronic liver diseases including liver fibrosis and cirrhosis. Therefore, in this study, we investigated the in vitro and in vivo antifibrotic efficacy of A-ENVs in thioacetamide-induced liver fibrosis models. A-ENVs significantly downregulated the expression of fibrogenic markers, such as matrix metalloproteinase-2, collagen-1, and alpha-smooth muscle actin. The systemic administration of A-ENVs led to high accumulation in fibrotic liver tissue and the restoration of liver functionality in liver fibrosis models through a marked reduction in α-SMA and collagen deposition. These results demonstrate the significant potential of A-ENVs for use as extracellular nanovesicles-based therapeutics in the treatment of liver fibrosis and possibly other intractable chronic liver diseases.


Assuntos
Metaloproteinase 2 da Matriz , Células-Tronco , Tecido Adiposo , Fibrose , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Cirrose Hepática/terapia
13.
J Clin Med ; 9(1)2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31948126

RESUMO

: BVAC-C is a B cell-based and monocyte-based immuno-therapeutic vaccine transfected with a recombinant human papillomavirus (HPV) 16/18 E6/E7 gene and loaded with alpha-galactosyl ceramide, which is a natural killer T cell ligand. This phase I study sought to determine the tolerability and immunogenicity of BVAC-C in platinum-resistant recurrent cervical cancer patients. Patients with HPV 16-positive or 18-positive recurrent or persistent cervical cancer who had received at least one prior platinum-based combination chemotherapy were enrolled. BVAC-C was injected intravenously three times every four weeks, and dose escalation was planned in a three-patient cohort design at doses of 1 × 107, 4 × 107, or 1 × 108 cells/dose. Eleven patients were enrolled, and six (55%) patients had received two or more lines of platinum-based chemotherapy prior to enrollment. Treatment-related adverse events (TRAEs) were observed in 21 cycles. Most TRAEs were mild fever (n = 6, 55%) or myalgia (n = 4, 36%). No dose-limiting toxicities occurred. The overall response rate was 11% among nine patients evaluable, and the duration of response was 10 months. Five patients (56%) achieved a stable disease for 4.2-11 months as their best overall response. The median progression-free survival in all patients was 6.8 months (95% CI, 3.2 to infinite months), and the overall survival rate at 6 and 12 months was 89% (95% CI, 71 to 100%) and 65% (95% CI, 39 to 100%), respectively. BVAC-C induced the activation of natural killer T cells, natural killer cells, and HPV 16/18 E6/E7-specific T cells upon vaccination in all patients evaluated. BVAC-C was well tolerated and demonstrated a durable anti-tumor activity with an immune response in HPV 16-positive or 18-positive recurrent cervical carcinoma patients. A Phase 2 efficacy trial is currently underway.

14.
Adv Funct Mater ; 29(20)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31839764

RESUMO

Using siRNA therapeutics to treat hematologic malignancies has been unsuccessful because blood cancer cells exhibit remarkable resistance to standard transfection methods. Herein we report the successful delivery of siRNA therapeutics with a dual-targeted, layer-by-layer nanoparticle (LbL-NP). The LbL-NP protects siRNA from nucleases in the bloodstream by embedding it within polyelectrolyte layers that coat a polymeric core. The outermost layer consists of hyaluronic acid (a CD44-ligand) covalently conjugated to CD20 antibodies. The CD20/CD44 dual-targeting outer layer provides precise binding to blood cancer cells, followed by receptor-mediated endocytosis of the LbL-NP. We use this siRNA delivery platform to silence B-cell lymphoma 2 (BCL-2), a pro-survival protein, in vitro and in vivo. The dual-targeting approach significantly enhanced internalization of BCL-2 siRNA in lymphoma and leukemia cells, which led to significant downregulation of BCL-2 expression. Systemic administration of the dual-targeted, siRNA-loaded nanoparticle induced apoptosis and hampered proliferation of blood cancer cells both in cell culture and in orthotopic non-Hodgkin's lymphoma animal models. These results provide the basis for approaches to targeting blood-borne cancers and other diseases, and suggest that LbL nanoassemblies are a promising approach for delivering therapeutic siRNA to hematopoetic cell types that are known to evade transfection by other means.

15.
J Biosci Bioeng ; 128(5): 613-621, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31128971

RESUMO

Decellularized esophageal matrices are ideal scaffolds for esophageal tissue engineering. Unfortunately, in order to improve transplantation possibilities, they require modification to reduce their degradation rate and immunogenicity. To date, no modifying agent has been approved to overcome these limitations. The objective of this study was to evaluate the ability of silver nanoparticles (AgNPs) to improve the structural stability and biocompatibility of decellularized rat esophagi. AgNPs have the advantage over currently used agents in that they bind with collagen fibers in a highly ordered manner, via non-covalent binding mechanisms forming multiple binding sites, while other agents provide only two-point connections between collagen molecules. Rat esophagi were decellularized, loaded with 5 µg/mL of AgNPs (100 nm), and then treated with an immobilization-complex buffer composed of ethyl carbodiimide hydrochloride and N-hydroxysuccinimide (EDC/NHS). Then, they were evaluated in terms of ultra-structural morphology, water uptake, in vitro resistance to enzymatic and thermal degradation, indentation strength, in vitro anti-calcification, cytocompatibility with rat bone marrow derived stromal cells (rat-BMSCs), angiogenic properties, and in vivo biocompatibility, and compared to scaffolds modified using glutaraldehyde and EDC/NHS complex buffer alone. AgNP-modified scaffolds showed an improved ultrastructure, good water uptake, and considerable resistance against in vitro degradation and indentation, and a high resistance against in vitro calcification. Moreover, they were cytocompatible for allogeneic rat-BMSCs. Additionally, AgNPs did not alter the angiogenic properties of the modified scaffolds and decreased host immune responses after their subcutaneous implantation. The structural properties and biocompatibility of decellularized esophageal matrices could be improved by conjugation with AgNPs.


Assuntos
Esôfago , Nanopartículas Metálicas/química , Animais , Colágeno/química , Masculino , Células-Tronco Mesenquimais , Ratos , Ratos Sprague-Dawley , Prata/química , Engenharia Tecidual , Alicerces Teciduais/química
17.
Int J Artif Organs ; 41(8): 421-430, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29807488

RESUMO

Decellularization of tissues can significantly improve regenerative medicine and tissue engineering by producing natural, less immunogenic, three-dimensional, acellular matrices with high biological activity for transplantation. Decellularized matrices retain specific critical components of native tissues such as stem cell niche, various growth factors, and the ability to regenerate in vivo. However, recellularization and functionalization of these matrices remain limited, highlighting the need to improve the characteristics of decellularized matrices. Incorporating nanoparticles into decellularized tissues can overcome these limitations because nanoparticles possess unique properties such as multifunctionality and can modify the surface of decellularized matrices with additional growth factors, which can be loaded onto the nanoparticles. Therefore, in this minireview, we highlight the various approaches used to improve decellularized matrices with incorporation of nanoparticles and the challenges present in these applications.


Assuntos
Matriz Extracelular/química , Nanopartículas , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Humanos , Regeneração , Medicina Regenerativa/métodos
18.
Nano Lett ; 18(4): 2637-2644, 2018 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-29521509

RESUMO

Conventional cancer targeting with nanoparticles has been based on the assumed enhanced permeability and retention (EPR) effect. The data obtained in clinical trials to date, however, have rarely supported the presence of such an effect. To address this challenge, we formulated intracellular nitric oxide-generating nanoparticles (NO-NPs) for the tumor site-specific delivery of NO, a well-known vasodilator, with the intention of boosting EPR. These nanoparticles are self-assembled under aqueous conditions from amphiphilic copolymers of poly(ethylene glycol) and nitrated dextran, which possesses inherent NO release properties in the reductive environment of cancer cells. After systemic administration of the NO-NPs, we quantitatively assessed and visualized increased tumor blood flow as well as enhanced vascular permeability than could be achieved without NO. Additionally, we prepared doxorubicin (DOX)-encapsulated NO-NPs and demonstrated consequential improvement in therapeutic efficacy over the control groups with considerably improved DOX intratumoral accumulation. Overall, this proof of concept study implies a high potency of the NO-NPs as an EPR enhancer to achieve better clinical outcomes.

19.
Artif Cells Nanomed Biotechnol ; 46(sup2): 273-284, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29587547

RESUMO

No ideal cross-linking agent has been identified for decellularized livers (DLs) yet. In this study, we evaluated structural improvements and biocompatibility of porcine DLs after cross-linking with silver nanoparticles (AgNPs). Porcine liver slices were decellularized and then loaded with AgNPs (100 nm) after optimization of the highest non-toxic concentration (5 µg/mL) using Human hepatocellular carcinoma (HepG2) and EAhy926 human endothelial cell lines. The cross-linking effect of AgNPs was evaluated and compared to that of glutaraldehyde and ethyl carbodiimide hydrochloride and N-hydroxysuccinimide. The results indicated that AgNPs improved the ultra-structure of DLs' collagen fibres with good porosity and increased DLs' resistance against in vitro degradation with good cytocompatibility. AgNPs decreased the host inflammatory reaction against implanted porcine DL slices in vivo and increased the polarization of M2 macrophages. Thus, structural and functional improvements of Porcine DLs could be achieved using AgNPs.


Assuntos
Fígado/citologia , Teste de Materiais , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Animais , Colagenases/metabolismo , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Suínos
20.
Medicine (Baltimore) ; 96(46): e8343, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29145245

RESUMO

STUDY DESIGN: Case description. OBJECTIVE: Acute calcific tendinitis of the longus colli muscle is a rare clinical entity that causes severe neck pain. This entity is not well recognized due to its nonspecific presentation such as acute neck pain, neck stiffness, and odynophagia. The importance of this disease with a review of the literature is presented. SUMMARY OF BACKGROUND DATA: Acute calcific tendinitis of the longus colli muscle is an inflammatory condition caused by deposition of calcium hydroxyapatite in the superior oblique tendon fibers of the longus colli muscle. It can be misdiagnosed as other life-threatening conditions including retropharyngeal abscess, resulting in unnecessary medical or surgical interventions. METHODS: We retrospectively reviewed the clinical data, radiological features, and laboratory reports of 8 patients who were diagnosed with acute calcific tendinitis of the longus colli muscle and seen at our institution between April 2008 and March 2015 in this article. We describe the clinical presentation, diagnosis, and treatment of acute calcific tendinitis of the longus colli muscle. RESULTS: There were 5 men and 3 women who ranged in age from 41 to 49 years (mean age: 44.5 years). The associated symptoms included neck pain, stiffness, odynophagia, and headache. The duration of symptoms varied from 2 days to 1 week. All patients showed calcific deposition inferior to the anterior arch of the atlas, and prevertebral effusion extending from C1 to C4. All patients were treated with NSAIDs and immobilization with a cervical brace, and most patients showed complete resolution of symptoms within 1 week. CONCLUSION: We report 8 cases of acute calcific tendinitis of the longus colli, and describe the symptoms and radiological findings in detail. Awareness of this rare, benign, and self-limiting disease entity with characteristic radiologic findings is essential for early diagnosis and to avoid unnecessary medical and surgical interventions.


Assuntos
Calcinose/complicações , Cervicalgia/etiologia , Tendinopatia/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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