Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Carbohydr Polym ; 340: 122270, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38858000

RESUMO

Targeted and stimuli-responsive drug delivery enhances therapeutic efficacy and minimizes undesirable side effects of cancer treatment. Although cellulose nanocrystals (CNCs) are used as drug carriers because of their robustness, spindle shape, biocompatibility, renewability, and nontoxicity, the lack of programmability and functionality of CNCs-based platforms hampers their application. Thus, high adaptability and the capacity to form dynamic 3D nanostructures of DNA may be advantageous, as they can provide functionalities such as target-specific and stimuli-responsive drug release. Using DNA nanotechnology, the functional polymeric form of DNA nanostructures can be replicated using rolling circle amplification (RCA), and the biologically and physiologically stable DNA nanostructures may overcome the challenges of CNCs. In this study, multifunctional polymeric DNAs produced with RCA were strongly complexed with surface-modified CNCs via electrostatic interactions to form polymeric DNA-decorated CNCs (pDCs). Particle size, polydispersity, zeta potential, and biostability of the nanocomplexes were analyzed. As a proof of concept, the dynamic structural functionalities of DNA nanostructures were verified by observing cancer-targeted intracellular delivery and pH-responsive drug release. pDCs showed anticancer properties without side effects in vitro, owing to their aptamer and i-motif functionalities. In conclusion, pDCs exhibited multifunctional anticancer activities, demonstrating their potential as a promising hybrid nanocomplex platform for targeted cancer therapy.


Assuntos
Celulose , DNA , Portadores de Fármacos , Liberação Controlada de Fármacos , Nanopartículas , Nanoestruturas , Celulose/química , Humanos , Nanopartículas/química , DNA/química , Nanoestruturas/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Polímeros/química , Concentração de Íons de Hidrogênio , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos
2.
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
3.
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
4.
Carbohydr Polym ; 299: 120178, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36876793

RESUMO

Advanced technologies for producing high-quality low molecular weight hyaluronic acid (LMW-HA) are required from the perspective of cost-efficiency and biosafety. Here, we report a new LMW-HA production system from high molecular weight HA (HMW-HA) using vacuum ultraviolet TiO2 photocatalysis with an oxygen nanobubble system (VUV-TP-NB). The VUV-TP-NB treatment for 3 h resulted in a satisfactory LMW-HA (approximately 50 kDa measured by GPC) yield with a low endotoxin level. Further, there were no inherent structural changes in the LMW-HA during the oxidative degradation process. Compared with conventional acid and enzyme hydrolysis methods, VUV-TP-NB showed similar degradation degree with viscosity though reduced process time by at least 8-fold. In terms of endotoxin and antioxidant effects, degradation using VUV-TP-NB demonstrated the lowest endotoxin level (0.21 EU/mL) and highest radical scavenging activity. This nanobubble-based photocatalysis system can thus be used to produce biosafe LMW-HA cost-effectively for food, medical, and cosmetics applications.


Assuntos
Endotoxinas , Ácido Hialurônico , Hidrólise , Vácuo , Oxigênio
5.
ACS Nano ; 16(8): 13211-13222, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35952305

RESUMO

Greater understanding of the mutual influence between DNA and the associated nanomaterial on the properties of each other can provide alternative strategies for designing and developing DNA nanomachines. DNA secondary structures are essential for encapsulating highly emissive silver nanoclusters (DNA/AgNCs). Likewise, AgNCs stabilize secondary DNA structures, such as hairpin DNA, duplex DNA, and parallel-motif DNA triplex. In this study, we found that the fluorescence of AgNCs encapsulated within a Hoogsteen triplex DNA structure can be turned on and off in response to pH changes. We also show that AgNCs can act as nanoscale rivets, linking two functionally distinctive DNA nanostructures. For instance, we found that a Hoogsteen triplex DNA structure with a seven-cytosine loop encapsulates red fluorescent AgNCs. The red fluorescence faded under alkaline conditions, whereas the fluorescence was restored in a near-neutral environment. Hairpin DNA and random DNA structures did not exhibit this pH-dependent AgNCs fluorescence. A fluorescence lifetime measurement and a small-angle X-ray scattering analysis showed that the triplex DNA-encapsulated AgNCs were photophysically convertible between bright and dark states. An in-gel electrophoresis analysis indicated that bright and dark convertibility depended on the AgNCs-riveted dimerization of the triplex DNAs. Moreover, we found that AgNCs rivet the triplex DNA and hairpin DNA to form a heterodimer, emitting orange fluorescence. Our findings suggest that AgNCs between two cytosine-rich loops can be used as nanorivets in designing noncanonical DNA origami beyond Watson-Crick base pairing.


Assuntos
Nanopartículas Metálicas , Prata , Prata/química , DNA/química , Pareamento de Bases , Citosina/química , Nanopartículas Metálicas/química , Espectrometria de Fluorescência/métodos
6.
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
7.
Int J Biol Macromol ; 208: 1096-1105, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35367269

RESUMO

Plant-based meats, which are nutritious foods from non-animal sources, provide clues for addressing the negative externalities associated with conventional meat production. Interest in plant-based meat has increased and is driving the rapid growth of its market. Plant-based meat should be equipped with a temperature-dependent scent release system similar to the scent release mechanism of conventional meat, to deliver a desirable meat-like flavor to consumers and obtain higher market acceptance. In this study, we prepared thermoresponsive gelatin-alginate hybrid hydrogels to control the release of scent molecules. The polymer network of gelatin-alginate hydrogels was reinforced by a semi-interpenetrating network (sIPN). sIPN formation conferred resistance to external stimuli, such as shear force, swelling, and temperature, resulting in a sustained release of the meat scent. In addition, controlled size microcapsules fabricated from the same composition via an electrostatic extrusion process showed a sustained release pattern of the loaded scent at 70 °C, and the scent release rate was precisely controlled within an approximately 2-fold range by adjusting the alginate concentration. These observations suggest the potential use of edible biological macromolecules as food additives that can control the release of scent molecules from the plant-based meat during cooking.


Assuntos
Alginatos , Gelatina , Preparações de Ação Retardada , Hidrogéis , Odorantes
8.
Carbohydr Polym ; 272: 118469, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34420728

RESUMO

The selection of sacrificial support materials is important in the fabrication of complex freeform structures. In this study, a dual droplet-based, freeform 3D printing method for pseudoplastic alginate biomaterial inks was developed using Bingham plastic cellulose nanocrystals (CNCs) as support nanomaterials. CNCs-CaCl2 mixture compositions and alginate concentrations were varied to enhance printability with rheological properties of shape fidelity and structural stability. The mixtures supported the shape of alginate and allowed CaCl2 diffusion-based cross-linking during 3D printing. The hydrogels showed rheological and physicochemical properties similar to those of pure alginate hydrogel, as CNCs were removed during post-printing processing. BSA-loaded multi-layered spheres, freeform 3D-printed for oral protein drug delivery, protected BSA in the gastric environment and provided controlled and sustained release of BSA into the intestinal environment as layer width and alginate concentration increased. This method can facilitate freeform 3D printing of diverse pseudoplastic biomaterial inks for biomedical applications.


Assuntos
Celulose , Alginatos , Hidrogéis , Impressão Tridimensional , Engenharia Tecidual
9.
ACS Nano ; 15(2): 1942-1951, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33492127

RESUMO

Due to powerful breakthroughs in nanotechnology, smart delivery mechanisms have rapidly emerged for use in diverse applications across biomedical research and therapeutic development. Recent efforts toward understanding stimuli-responsive strategies have led to substantial improvements in their conceptual application and in vitro efficiency. Because disease targets for therapy are often localized in specific cells, organs, or tissues, an enhanced permeability and retention (EPR)-based strategy remains inadequate for accurate drug delivery and release to target regions, resulting in an insufficient drug concentration reaching the target region and undesired side effects. To address these issues, more precise and remote-controlled stimuli-responsive systems, which recognize and react to changes in the pathophysiological microenvironment, were recently elucidated as feasible on-demand drug-delivery systems. In this Perspective, we focus on progress toward stimuli-responsive drug-delivery systems that utilize dynamic DNA molecules by exploiting DNA nanotechnology. DNA structures can be precisely reconfigured by external and internal stimuli to drive the release of a loaded drug in a target region with appropriate microenvironments. We describe the chemical, physical, and biological engineering principles and strategies for constructing DNA-assisted nanocarriers. We also provide a summary of smart nanocarrier systems, organized with respect to the structural changes in the DNA strand in the microenvironment, resulting from changes in pH and temperature and the presence of intracellular oligonucleotides. To do so, we highlight recent advances in related biomedical research and applications as well as discuss major challenges and opportunities for DNA-assisted nanocarriers to guide the development of future in vivo therapies and clinical translation strategies.


Assuntos
Pesquisa Biomédica , Preparações Farmacêuticas , DNA , Sistemas de Liberação de Medicamentos , Nanotecnologia , Temperatura
10.
Macromol Rapid Commun ; 42(2): e2000457, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33230833

RESUMO

Targeted, stimulus-responsive DNA nanogels hold considerable promise for cancer therapeutics. To expand their functionality including thermoresponsiveness, here, multifunctional DNA nanogels are developed for potential application toward cancer-targeted delivery and stimuli-responsive release of cancer therapeutics. Three types of functionalized DNA nanobuilding units are formed into DNA nanogels of ≈200 nm via sequence-dependent self-assembly. The sequence-dependent assembly of nanobuilding units is precisely designed for controlled assembly and thermal disassembly at physiological temperatures. The supramolecular structure exhibits multifunctionalities including temperature-induced disassembly, aptamer-mediated cancer cell targeting, and light-triggered temperature increase. The nanogels support co-loading of cancer therapeutics including anti-sense oligonucleotides and doxorubicin along with stimuli-responsive release of loaded drugs through temperature-responsive structural disassembly and pH-responsive deintercalation. The nanogels exhibit efficient aptamer-mediated cancer-specific intracellular delivery and combinational anticancer effects upon light triggering. The developed DNA nanogels, thus, constitute potential noncationic nanovectors for targeted delivery of combinational cancer therapeutics.


Assuntos
Doxorrubicina , Neoplasias , DNA , Doxorrubicina/farmacologia , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Nanogéis , Neoplasias/tratamento farmacológico
11.
Carbohydr Polym ; 247: 116684, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829812

RESUMO

Surface-modified cellulose nanocrystals (CNCs) were developed for efficient delivery of polymeric siRNA in cancer cells. Cationic CNCs were synthesized using the sequential process of hydrothermal desulfation and chemical modification following which, polymeric siRNA obtained using from a two-step process of rolling circle transcription and Mg2+ chelation was complexed with the modified CNCs by electrostatic interaction. The complexation efficiency was optimized for high drug loading and release in the cytoplasmic environment. The resultant nanocomplex showed significantly enhanced enzymatic stability, gene knockdown efficacy, and apoptosis-induced in vitro therapeutic effect. Our results suggest CNCs as a promising carbohydrate-based delivery platform which could be utilized for RNAi-mediated cancer therapeutics.


Assuntos
Antineoplásicos/farmacologia , Cátions/química , Celulose/química , Preparações de Ação Retardada/farmacologia , Nanopartículas/química , Polímeros/síntese química , RNA Interferente Pequeno/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/uso terapêutico , Liberação Controlada de Fármacos , Técnicas de Silenciamento de Genes/métodos , Humanos , Neoplasias/tratamento farmacológico , Polímeros/química , RNA Interferente Pequeno/síntese química , Eletricidade Estática , Propriedades de Superfície
12.
Int J Pharm ; 588: 119736, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32758596

RESUMO

Although oral administration is favorable mode of insulin delivery, it is the most challenging route, owing to poor oral bioavailability. In this study, a chitosan (CS)-based insulin delivery system was developed by ionic crosslinking with phytic acid (PA). CS-PA microspheres were optimized with different crosslinking conditions of CS and PA using response surface methodology to retain insulin during preparation and gastric digestion. Furthermore, the in vitro release profile, morphological structure, cytotoxicity, and intestinal permeability of the optimized microspheres, and its hypoglycemic effect in diabetic rats were evaluated. Under optimal conditions, the entrapment efficiency was 97.1%, and 67.0% of insulin was retained in the microspheres after 2 h of gastric digestion followed by a sustained-release in intestinal fluid. Insulin was primarily distributed in the microsphere core with a monodisperse diameter of 663.3 µm. The microspheres increased the permeability of insulin across Caco-2/HT-29 monolayers by 1.6 times with negligible cytotoxicity. The microspheres had a relative pharmacological bioavailability of 10.6% and significantly reduced blood glucose levels with a long-lasting hypoglycemic effect after oral administration in diabetic rats. This study demonstrated that an optimized formulation of a simple ionic crosslinking system using CS and PA could facilitate efficient oral delivery of insulin.


Assuntos
Quitosana , Diabetes Mellitus Experimental , Portadores de Fármacos , Hipoglicemiantes , Insulina , Administração Oral , Animais , Células CACO-2 , Quitosana/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/uso terapêutico , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Microesferas , Tamanho da Partícula , Ácido Fítico/uso terapêutico , Ratos
13.
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
15.
ACS Biomater Sci Eng ; 4(12): 4163-4173, 2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33418815

RESUMO

Orally administered antisense therapy has been introduced as an effective approach for treating cancer in the gastrointestinal tract. However, its practical application has been limited by the instability of oligonucleotides and their inefficient delivery. To overcome these problems, we synthesized size-dependent, oligonucleotide nanoparticle-patterned chitosan/phytic acid (ODN/CS/PA) capsules with protective shields via a three-step process of self-assembly, nanoparticle encapsulation, and shell formation. The multicompartmental capsule size and oligonucleotide nanoparticle-loading pattern were controlled by applying different potentials during the electrostatic extrusion process used for nanoparticle encapsulation. Over 95% of encapsulated oligonucleotides were protected from nuclease digestion (DNase I) and, depending on their size, showed 40-75% protection against simulated gastric fluid. Their controlled release from capsules correlated with the cellular delivery of released nanoparticles and the inhibition of protein expression in cancer cells. Specifically, large capsules showed approximately 32-fold greater delivery to cancer cells than nonencapsulated nanoparticles. We also confirmed delivery of oligonucleotide nanoparticles to the small intestine and colon of rats following oral administration. These findings demonstrate that the multicompartmental ODN/CS/PA capsules can facilitate efficient oral delivery of oligonucleotides for cancer treatment.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...