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1.
J Nanobiotechnology ; 22(1): 518, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210464

RESUMEN

Deoxyribonucleotide (DNA) is uniquely programmable and biocompatible, and exhibits unique appeal as a biomaterial as it can be precisely designed and programmed to construct arbitrary shapes. DNA hydrogels are polymer networks comprising cross-linked DNA strands. As DNA hydrogels present programmability, biocompatibility, and stimulus responsiveness, they are extensively explored in the field of biomedicine. In this study, we provide an overview of recent advancements in DNA hydrogel technology. We outline the different design philosophies and methods of DNA hydrogel preparation, discuss its special physicochemical characteristics, and highlight the various uses of DNA hydrogels in biomedical domains, such as drug delivery, biosensing, tissue engineering, and cell culture. Finally, we discuss the current difficulties facing DNA hydrogels and their potential future development.


Asunto(s)
Materiales Biocompatibles , ADN , Hidrogeles , Ingeniería de Tejidos , Hidrogeles/química , ADN/química , Humanos , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/química , Animales , Sistemas de Liberación de Medicamentos/métodos , Ingeniería Biomédica/métodos , Técnicas Biosensibles/métodos , Técnicas de Cultivo de Célula/métodos
2.
Mol Pharm ; 20(8): 4007-4020, 2023 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-37427910

RESUMEN

Distant metastasis of malignant tumors is considered to be the main culprit for the failure of current antitumor treatments. Conventional single treatments often exhibit limited efficacy in inhibiting tumor metastasis. Therefore, there is a growing interest in developing collaborative antitumor strategies based on photothermal therapy (PTT) and free-radical-generated photodynamic therapy (PDT), especially utilizing oxygen-independent nanoplatforms, to address this challenge. Such antitumor strategies can enhance the therapeutic outcomes by ensuring the cytotoxicity of free radicals even in the hypoxic tumor microenvironment, thereby improving the effective suppression of primary tumors. Additionally, these approaches can stimulate the production of tumor-associated antigens and amplify the immunogenic cell death (ICD) effects, potentially feasible for enhancing the therapeutic outcomes of immunotherapy. Herein, we fabricated a functional nanosystem that co-loads IR780 and 2,2'-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH) to realize PTT-triggered thermodynamic combination therapy via the oxygen-independent pathway for the elimination of primary tumors. Furthermore, the nanocomposites were surface-decorated with a predesigned complex peptide (PLGVRGC-anti-PD-L1 peptide, MMP-sensitive), which facilitated the immunotherapy targeting distant tumors. Through the specific recognition of matrix metalloproteinase (MMP), the sensitive segment on the obtained aNC@IR780A was cleaved. As a result, the freed anti-PD-L1 peptide effectively blocked immune checkpoints, leading to the infiltration and activation of T cells (CTLs). This nanosystem was proven to be effective at inhibiting both primary tumors and distant tumors, providing a promising combination strategy for tumor PTT/TDT/immunotherapy.


Asunto(s)
Nanopartículas , Fototerapia , Línea Celular Tumoral , Inmunoterapia , Oxígeno , Péptidos , Polímeros , Termodinámica , Microambiente Tumoral , Humanos
3.
Mol Pharm ; 20(8): 3914-3924, 2023 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-37384449

RESUMEN

Nanoparticles (NPs) show great advantages in cancer treatment by enabling controlled and targeted delivery of payloads to tumor sites through the enhanced permeability and retention (EPR) effect. In this study, highly effective pH-responsive and biodegradable calcium orthophosphate@liposomes (CaP@Lip) NPs with a diameter of 110 ± 20 nm were designed and fabricated. CaP@Lip NPs loaded with hydrophobic paclitaxel and hydrophilic doxorubicin hydrochloride achieved excellent drug loading efficiencies of 70 and 90%, respectively. Under physiological conditions, the obtained NPs are negatively charged. However, they switched to positively charged when exposed to weak acidic environments by which internalization can be promoted. Furthermore, the CaP@Lip NPs exhibit an obvious structural collapse under acid conditions (pH 5.5), which confirms their excellent biodegradability. The "proton expansion" effect in endosomes and the pH-responsiveness of the NPs facilitate the release of encapsulated drugs from individual channels. The effectiveness and safety of the drug delivery systems were demonstrated through in vitro and in vivo experiments, with a 76% inhibition of tumor growth. These findings highlight the high targeting ability of the drug-loaded NPs to tumor sites through the EPR effect, effectively suppressing tumor growth and metastasis. By combining CaP NPs and liposomes, this study not only resolves the toxicity of CaP but also enhances the stability of liposomes. The CaP@Lip NPs developed in this study have significant implications for biomedical applications and inspire the development of intelligent and smart drug nanocarriers and release systems for clinical use.


Asunto(s)
Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Doxorrubicina/química , Neoplasias de la Mama/tratamiento farmacológico , Liposomas/uso terapéutico , Paclitaxel/uso terapéutico , Paclitaxel/farmacología , Calcio , Fosfatos , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Concentración de Iones de Hidrógeno
4.
BMC Infect Dis ; 23(1): 70, 2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36747151

RESUMEN

BACKGROUND: Serum lipids variations are closely related to the sepsis progression; however, their value for patients with pyogenic liver abscesses (PLA) has rarely been studied. We investigated the serum lipid level variations in patients with PLA and its predictive value to the disease. METHODS: The study included 328 patients with PLA hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2021; 35 (10.67%) in the severe group (SG) and 293 (89.33%) in the non-severe group (nSG). Their clinical records were analyzed retrospectively, and dynamic curves were drawn to clarify the changes in different indicators during the course of the disease. RESULTS: High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a) (Lp(a)) in the SG were significantly lower than those in nSG (P < 0.001). Total cholesterol (TC) at baseline (OR = 0.184, P < 0.001) was an independent risk factor for severe patients and had the highest predictive value, with an area under the curve of 0.859 and a cut-off value of 2.70 mmol/L (sensitivity = 94.3%, specificity = 63.5%). For patients who met the criteria for drainage surgery, TC, HDL-C and LDL-C levels continued to decrease with antibiotic therapy alone before drainage and began to increase after the surgery. CONCLUSIONS: Low TC level on admission is an independent risk factor for the progression of severe illness in PLA patients, with the highest predictive value surpassing other routine clinical indices. Abscess drainage should be performed as soon as possible for patients whose TC continues to decline after medical treatment.


Asunto(s)
Colesterol , Absceso Piógeno Hepático , Humanos , Estudios Retrospectivos , LDL-Colesterol , Triglicéridos , Pronóstico , Relevancia Clínica , HDL-Colesterol , Poliésteres
5.
Chembiochem ; 22(16): 2608-2613, 2021 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-34155741

RESUMEN

The conditional control of protein function in response to the physiological change of cells is of great interest for studying protein function in biological settings and developing protein therapeutics. We report herein that catalase (CAT) DNAzyme can potentiate the generation of reactive oxygen species (ROS) in living cells by knocking down catalase expression, which could further activate a reactive oxygen species (ROS)-responsive pro-protein, RNase A-NBC, in situ. Using an optimized lipid nanoparticle delivery system to simultaneously introduce CAT DNAzyme and RNase A-NBC into cells, we show that the pro-protein, RNase A-NBC, could be activated in a significantly enhanced manner to prohibit tumor cell growth in different types of cancer cells. We believe the methodology of regulating pro-protein activity using DNAzyme biocatalysis to differentiate intracellular environment could further be extended to other functional proteins, and even fundamental investigations in living systems to develop pro-protein therapeutics.


Asunto(s)
Liposomas , Nanopartículas
6.
Nanomedicine ; 34: 102382, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33771706

RESUMEN

Invasive infections caused by antibiotic-resistant Staphylococcus aureus have posed a great threat to human health. To tackle this problem, a cationic liposomal Curcumin (C-LS/Cur) was developed and its effect against antibiotic-resistant S. aureus was investigated in this study. As expected, C-LS/Cur exhibited greater bactericidal capacity compared with its counterparts, probably because the negatively charged S. aureus favors electrostatic interactions rather than intercalation with cationic liposomal vesicles at the beginning of endocytic process, thereby effectively delivering Cur to its targets. We confirmed this hypothesis by monitoring zeta potential variation, collecting visual evidences through CLSM, FCM and TEM, and determining binding kinetics by BLI. Moreover, an excellent therapeutic efficacy of C-LS/Cur against invasive murine infection was also observed, which was due to the enhanced accumulation and retention in the targets. Therefore, cationic liposomes have great potential for the clinical application in the treatment of invasive antibiotic-resistant S. aureus infections.


Asunto(s)
Liposomas , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológico , Cationes , Endocitosis , Humanos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana
7.
Angew Chem Int Ed Engl ; 60(51): 26740-26746, 2021 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-34622541

RESUMEN

The delivery of protein into mammalian cells enables the dissection and manipulation of biological processes; however, this potency is challenged by the lack of an efficient protein delivery tool and a means to monitor its intracellular trafficking. Herein, we report that the hierarchical self-assembly of tetraphenylethylene (TPE)-featured metal-organic cages (MOCs) and ß-cyclodextrin-conjugated polyethylenimine can generate fluorescent supramolecular nanoparticles (FSNPs) to deliver protein into neural cells, a cell line that is hard to transfect using conventional strategy. Further, the aggregation-induced emission (AIE) of TPE enabled the fluorescent monitoring of cytosolic protein release. It is found that FSNPs can deliver and release protein into cytosol for subcellular targeting as fast as 18 h post-delivery. Moreover, the delivery of molecular chaperone DJ-1 using FSNPs activates MAPK/ERK signaling of neural cells to protect cells from oxidative stress.


Asunto(s)
Colorantes Fluorescentes/farmacología , Nanopartículas/química , Células-Madre Neurales/efectos de los fármacos , Estilbenos/farmacología , Línea Celular Tumoral , Colorantes Fluorescentes/química , Humanos , Sustancias Macromoleculares/química , Sustancias Macromoleculares/farmacología , Células-Madre Neurales/metabolismo , Estrés Oxidativo/efectos de los fármacos , Polietileneimina/química , Polietileneimina/farmacología , Estilbenos/química , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacología
8.
J Mater Chem B ; 12(25): 6146-6154, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38842181

RESUMEN

Supramolecular polymers (SPs) are an emerging class of drug transporters employed to improve drug therapy. Through the rational design of self-assembling monomers, one can optimize the properties of the resulting supramolecular nanostructures, such as size, shape, surface chemistry, release, and, therefore, biological fates. This study highlights the design of isomeric SN38 prodrugs through the conjugation of hydrophilic oligo(ethylene glycol) (OEG) with hydroxyls at positions 10 and 20 on hydrophobic SN-38. Self-assembling prodrug (SAPD) isomers 10-OEG-SN38 and 20-OEG-SN38 can self-assemble into giant nanotubes and filamentous assemblies, respectively, via aromatic associations that dominate self-assembly. Our study reveales the influence of modification sites on the assembly behavior and ability of the SN38 SAPDs, as well as drug release and subsequent in vitro and in vivo antitumor effects. The SAPD modified at position 20 exhibits stronger π-π interactions among SN38 units, leading to more compact packing and enhanced assembly capability, whereas OEG at position 10 poses steric hindrance for aromatic associations. Importantly, owing to its higher chemical and supramolecular stability, 20-OEG-SN38 outperforms 10-OEG-SN38 and irinotecan, a clinically used prodrug of SN38, in a CT26 tumor model, demonstrating enhanced tumor growth inhibition and prolonged animal survival. This study presents a new strategy of using interactions among drug molecules as dominating features to create supramolecular assemblies. It also brings some insights into creating effective supramolecular drug assemblies via the engineering of self-assembling building blocks, which could contribute to the optimization of design principles for supramolecular drug delivery systems.


Asunto(s)
Irinotecán , Profármacos , Profármacos/química , Profármacos/farmacología , Profármacos/síntesis química , Irinotecán/química , Irinotecán/farmacología , Humanos , Animales , Ratones , Isomerismo , Proliferación Celular/efectos de los fármacos , Liberación de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Ratones Endogámicos BALB C , Tamaño de la Partícula , Sustancias Macromoleculares/química , Sustancias Macromoleculares/síntesis química , Sustancias Macromoleculares/farmacología , Supervivencia Celular/efectos de los fármacos , Línea Celular Tumoral , Polietilenglicoles/química , Camptotecina/química , Camptotecina/farmacología , Camptotecina/análogos & derivados , Ratones Desnudos
9.
Food Chem ; 460(Pt 2): 140570, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39089022

RESUMEN

Residue of sulfamethazine (SMZ), a typical short-acting drug to prevent bacterial infections, in food is a threat to human health. A ternary heterogeneous metal-organic framework hybrid (Zn/Fe-MOF@PDANSs) of Zn-TCPP-MOF, MIL-101 (Fe) and polydopamine nanoparticles (PDANSs) was proposed to establish an aptasensor for the sensitive and selective detection of SMZ. In this sensor, Zn-TCPP-MOF and FAM emitted fluorescence at 609 nm and 523 nm, respectively, and the fluorescence of FAM-ssDNA could be quenched when it was adsorbed on the surface of MOF hybrid. In the presence of SMZ, the fluorescence of FAM-ssDNA recovered due to the dropping from MOF hybrid, while the fluorescence of MOF hybrid remained. With this strategy, a wide concentration range and high sensitivity of SMZ were detection. And the ternary Zn/Fe-MOF@PDANSs sensor exhibited more excellent performance than binary Zn/Fe-MOF aptasensor. In addition, the sensor showed pleasurable selectivity, and was utilized for SMZ determination in authentic chicken and pork samples, implying the fascinating potential in practical application.


Asunto(s)
Aptámeros de Nucleótidos , Pollos , Contaminación de Alimentos , Indoles , Estructuras Metalorgánicas , Nanopartículas , Polímeros , Sulfametazina , Estructuras Metalorgánicas/química , Indoles/química , Sulfametazina/análisis , Sulfametazina/química , Polímeros/química , Animales , Nanopartículas/química , Contaminación de Alimentos/análisis , Aptámeros de Nucleótidos/química , Porcinos , Técnicas Biosensibles/instrumentación , Fluorescencia , Espectrometría de Fluorescencia
10.
Biomater Sci ; 11(3): 1031-1041, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36545821

RESUMEN

Pseudomonas aeruginosa (PA) biofilms cause many persistent chronic infections in humans, especially in cystic fibrosis (CF) patients. The biofilms form a strong barrier which may inhibit antimicrobial agents from penetrating the biofilms and killing PA bacteria that reside deep within the biofilms. Concomitant therapies based on tobramycin (TOB) and azithromycin (AZM) have demonstrated beneficial effects in CF patients with chronic PA infections. However, the co-delivery of TOB and AZM has rarely been reported. In this study, we constructed a self-assembled pH-sensitive nano-assembly (DPNA) based on a dimeric prodrug (AZM-Cit-TOB) by simply inserting citraconic amide bonds between AZM and TOB. Moreover, the cationic surface of DPNA was further modified with anionic albumin (HSA) via electrostatic interactions to form an electrostatic complex (termed HSA@DPNA) for better biocompatibility. Upon arrival at the infected tissues, the citraconic amide bonds would be cleaved at acidic pH, resulting in the release of TOB and AZM for bacteria killing and biofilm eradication. As expected, HSA@DPNA showed comparable antibacterial abilities against the P. aeruginosa strain PAO1 in both planktonic and biofilm modes of growth compared to the TOB/AZM mixture in vitro. Moreover, HSA@DPNA exhibited excellent therapeutic efficacy on mice with PAO1-induced lung infection compared to the TOB/AZM mixture, and no detectable toxicity to mammalian cells/animals was observed during the therapeutic process. In summary, our study provides a promising method for the co-delivery of AZM and TOB in concomitant therapies against PAO1-related infection.


Asunto(s)
Fibrosis Quística , Profármacos , Humanos , Animales , Ratones , Profármacos/farmacología , Profármacos/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Azitromicina/farmacología , Azitromicina/uso terapéutico , Tobramicina/química , Tobramicina/farmacología , Tobramicina/uso terapéutico , Biopelículas , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/microbiología , Polímeros/farmacología , Concentración de Iones de Hidrógeno , Pseudomonas aeruginosa , Pruebas de Sensibilidad Microbiana , Mamíferos
11.
Macromol Biosci ; 23(4): e2200442, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36623250

RESUMEN

Developing proper wound management via wound dressings represents a global challenge. Ideal wound dressings shall encompass multiple integrated functionalities for variable, complex scenarios; however, this is challenging due to the complex molecular design and synthesis process. Herein, polymer composites, cross-linked poly(styrene oxide-co-hexaphenylcyclotrisiloxane)/crosslinked poly(hexaphenylcyclotrisiloxane) (cP(SO-co-HPCTS)/cPHPCTS) with multiple functionalities are prepared by a one-step, open-air method using catalytic ring-opening polymerization. The introduction of a mobile polymer cP(SO-co-HPCTS) endows the composite with good flexibility and self-healing properties at human body temperature. The hydrophobic groups in the main chain provide hydrophobicity and good water resistance, while the hydroxyl groups contained in the end groups enable good adhesion properties. Drugs can be efficiently loaded by blending and then sustainably release from the polymer composite. The material can rapidly degrade in a tetrahydrofuran solution of tetrabutylammonium fluoride due to its SiOSi bonds. The facile, one-step, open-air synthesis procedure and multiple functional properties integrated into the composites provide good prospects for their extensive application and batch production as wound dressing materials.


Asunto(s)
Polímeros , Cicatrización de Heridas , Humanos , Preparaciones de Acción Retardada/farmacología , Agua/química , Vendajes
12.
ACS Appl Bio Mater ; 4(4): 3166-3177, 2021 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-35014404

RESUMEN

Due to their various applications in human healthcare and industrial fields, engineering surfaces with antiadhesion and antibacteria properties is still a challenging task. In this work, the fluoropolymer with low surface energy and poly(poly(ethylene glycol) methyl ether methacrylate) (PEGMA) with electrostatic repulsion and interfacial hydration was chosen as a common antiadhesion block and quaternary ammonium salt with bactericide properties as a sterilization block. The triblock copolymers of poly(2-(dimethylamino)ethyl methacrylate)-b-poly(poly(oligo ethylene glycol) methyl ether methacrylate)-b-poly(dodecafluoroheptyl methacrylate) (PDMAEMA-b-PEGMA-b-PDFHMA) were synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization method. Then, the synthesized triblock copolymers were quaternized to obtain the antibacterial materials (QPDMAEMA-b-PEGMA-b-PDFHMA). It has been found that the QPDMAEMA-b-PEGMA-b-PDFHMA triblock copolymer coating has excellent antiadhesion and antibacterial properties against S. aureus and E. coli. The synergistic effects of fluoropolymer and PEGMA can enhance the antifouling properties of the coating. At the same time, it has a good antifouling effect on platelets and red blood cells. In addition, the triblock copolymer coating has long-term stability in high ionic strength solution of PBS in dynamic conditions. These kind of materials with antifouling and antibacterial properties may have potential applications on the surface of various public utilities and medical equipment.


Asunto(s)
Antibacterianos/farmacología , Materiales Biocompatibles/farmacología , Escherichia coli/efectos de los fármacos , Polímeros/farmacología , Compuestos de Amonio Cuaternario/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Polímeros/química , Compuestos de Amonio Cuaternario/química , Sales (Química)/química , Sales (Química)/farmacología
13.
Adv Sci (Weinh) ; 8(23): e2102035, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34713634

RESUMEN

The most critical factor determining the success of biodegradable bone implants is the host tissue response, which greatly depends on their degradation behaviors. Here, a new magnesium-based implant, namely magnesium-silicon-calcium (Mg-0.2Si-1.0Ca) alloy, that coordinates its biodegradation along with the bone regenerative process via a self-assembled, multilayered bone-implant interface is designed. At first, its rapid biocorrosion contributes to a burst release of Mg2+ , leading to a pro-osteogenic immune microenvironment in bone. Meanwhile, with the simultaneous intervention of Ca and Si in the secondary phases of the new alloy, a hierarchical layered calcified matrix is rapidly formed at the degrading interface that favored the subsequent bone mineralization. In contrast, pure Mg or Mg-0.2Si alloy without the development of this interface at the beginning will unavoidably induce detrimental bone loss. Hence, it is believed this biomimicking interface justifies its bioadaptability in which it can modulate its degradation in vivo and accelerate bone mineralization.


Asunto(s)
Implantes Absorbibles , Materiales Biomiméticos/uso terapéutico , Enfermedades Óseas Metabólicas/terapia , Interfase Hueso-Implante/fisiología , Microambiente Celular/fisiología , Magnesio , Aleaciones , Animales , Calcificación Fisiológica/fisiología , Modelos Animales de Enfermedad , Femenino , Ratas , Ratas Sprague-Dawley
14.
Biomaterials ; 276: 121038, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34339925

RESUMEN

Macrophage has been gradually recognized as a central regulator in tissue regeneration, and the study of how macrophage mediates biomaterials-induced bone regeneration through immunomodulatory pathway becomes popular. However, the current understanding on the roles of different macrophage phenotypes in regulating bone tissue regeneration remains controversial. In this study, we demonstrate that sequential infiltration of heterogeneous phenotypes of macrophages triggered by bio-metal ions effectively facilitates bone healing in bone defect. Indeed, M1 macrophages promote the recruitment and early commitment of osteogenic and angiogenic progenitors, while M2 macrophages and osteoclasts support the deposition and mineralization of the bone matrix, as well as the maturation of blood vessels. Moreover, we have identified a group of bone biomaterial-related multinucleated cells that behave similarly to M2 macrophages with wound-healing features rather than participate in the bone resorption cascade similarly to osteoclasts. Our study shows how sequential activation of macrophage-osteoclast lineage contribute to a highly orchestrated immune response in the bone tissue microenvironment around biomaterials to regulate the complex biological process of bone healing. Therefore, we believe that the temporal activation pattern of heterogeneous macrophage phenotypes should be considered when the next generation of biomaterials for bone regeneration is engineered.


Asunto(s)
Materiales Biocompatibles , Regeneración Ósea , Activación de Macrófagos , Macrófagos , Osteogénesis , Fenotipo
15.
Zhonghua Gan Zang Bing Za Zhi ; 18(2): 105-8, 2010 Feb.
Artículo en Zh | MEDLINE | ID: mdl-20196948

RESUMEN

OBJECTIVE: To investigate the effects of different PAP domains on hepatitis B virus replication. METHODS: The full length and two truncated PAP mutants were cloned into a eukaryotic expression plasmid, and were transfected into HepG2.2.15 cells using lipofectamine 2000. 3 days after transfection, the medium and cells were collected. HBsAg and HBeAg were measured using ELISA. The titers of HBV DNA were quantified using fluorogenic quantitative PCR (FQ-PCR). HepG2 cells were used to determine the cytotoxicity of the plasmids transfection by MTT assays. RESULTS: The inhibitory effect on HBV replication of the C-terminal 25 amino acids deleted PAP mutant (pXF3H-PAP14) was not significantly different from that of the full length PAP (pXF3H-PAP12) (Chi-square test = 0.5, 2.0, 0.02, probability value more than 0.05), however, the cytotoxicity of pXF3H-PAP14 was lower than that of pXF3H-PAP12 (Chi-square test = 7.7, probability value less than 0.01). Both N-terminal 69 amino acids deleted mutant and C-terminal 25 amino acids deleted mutant had no cytotoxicity and no antiviral activity. CONCLUSION: C-terminal 25 amino acid of PAP is related to cytotoxicity but not related to antiviral activity of PAP. N-terminal 69 amino acid of PAP is related to the anti-HBV effect of PAP.


Asunto(s)
Antivirales/farmacología , Virus de la Hepatitis B/fisiología , Proteínas Inactivadoras de Ribosomas Tipo 1/genética , Proteínas Inactivadoras de Ribosomas Tipo 1/farmacología , Replicación Viral/efectos de los fármacos , Secuencia de Aminoácidos , Western Blotting , ADN Viral/efectos de los fármacos , ADN Viral/metabolismo , Células Hep G2 , Antígenos de Superficie de la Hepatitis B/metabolismo , Antígenos e de la Hepatitis B/metabolismo , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Humanos , Liposomas , Plásmidos/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Inactivadoras de Ribosomas Tipo 1/metabolismo , Eliminación de Secuencia , Transfección
16.
ACS Appl Mater Interfaces ; 12(47): 52479-52491, 2020 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-33196186

RESUMEN

The development of near-infrared (NIR) laser triggered phototheranostics for multimodal imaging-guided combination therapy is highly desirable. However, multiple laser sources, as well as inadequate therapeutic efficacy, impede the application of phototheranostics. Here, we develop an all-in-one theranostic nanoagent PEGylated DCNP@DMSN-MoOx NPs (DCDMs) with a flower-like structure fabricated by coating uniformly sized down-conversion nanoparticles (DCNPs) with dendritic mesoporous silica (DMSN) and then loading the ultrasmall oxygen-deficient molybdenum oxide nanoparticles (MoOx NPs) inside through an electrostatic interaction. Owing to the doping of Nd ions, when excited by an 808 nm laser, DCNPs emit bright NIR-II emissions (1060 and 1300 nm), which have characteristic high spatial resolution and deep tissue penetration. In terms of treatment, MoOx NPs could be specifically activated by excessive hydrogen peroxide (H2O2) in the tumor microenvironment, thus generating 1O2 via the Russell mechanism. In addition, the excessive glutathione (GSH) in the tumor cells could be depleted through the Mo-mediated redox reaction, thus effectively decreasing the antioxidant capacity of tumor cells. Importantly, the excellent photothermal properties (photothermal conversion efficiency of 51.5% under an 808 nm laser) synergistically accelerate the generation of 1O2. This cyclic redox reaction of molybdenum indeed ensured the high efficacy of tumor-specific therapy, leaving the normal tissues unharmed. MoOx NPs could also efficiently catalyze tumor endogenous H2O2 into a considerable amount of O2 in an acidic tumor microenvironment, thus relieving hypoxia in tumor tissues. Moreover, the computed tomography (CT) and T1-weighted magnetic resonance imaging (MRI) effect from Gd3+ and Y3+ ions make DCNPs act as a hybrid imaging agent, allowing comprehensive analysis of tumor lesions. Both in vitro and in vivo experiments validate that such an "all-in-one" nanoplatform possesses desirable anticancer abilities under single laser source irradiation, benefiting from the NIR-II fluorescence/CT/MR multimodal imaging-guided photothermal/chemodynamic synergistic therapy. Overall, our strategy paves the way to explore other noninvasive cancer phototheranostics.


Asunto(s)
Materiales Biocompatibles/química , Nanopartículas/química , Microambiente Tumoral , Animales , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/uso terapéutico , Línea Celular , Supervivencia Celular/efectos de los fármacos , Medios de Contraste/química , Glutatión/química , Humanos , Peróxido de Hidrógeno/química , Ratones , Molibdeno/química , Imagen Multimodal , Nanopartículas/metabolismo , Nanopartículas/uso terapéutico , Nanopartículas/toxicidad , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Óxidos/química , Fotoquimioterapia , Terapia Fototérmica , Polietilenglicoles/química , Porosidad , Dióxido de Silicio/química , Oxígeno Singlete/química , Oxígeno Singlete/metabolismo , Microambiente Tumoral/efectos de los fármacos
17.
ACS Appl Mater Interfaces ; 12(6): 7617-7630, 2020 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-31951700

RESUMEN

Inhibiting the attachment of bacteria and the formation of biofilms on surfaces of materials and devices is the key to ensure public safety and is also the focus of attention and research. Here we report on the synthesis of multifunctional antibacterial materials based on water dispersible random copolymers containing a fluorinated block, poly(acrylic acid-co-1H,1H,2H,2H-perfluorododecyl acrylate) (PAA-co-PFDA), and poly(hexamethylene biguanide) hydrochloride (PHMB). PAA-co-PFDA copolymers were synthesized through a simple free radical polymerization. After lightly cross-linking of PAA-co-PFDA and complexation with PHMB, multifunctional antibacterial PAA-co-PFDA/PHMB complex nanoparticles were generated, which can form transparent coatings on various substrates. The resultant coating has aggregation-induced emission character which can be used to observe the uniformity of the coating on a catheter and has a potential application as a fluorescence probe. It has been demonstrated that the PAA-co-PFDA/PHMB complex nanoparticle coatings can resist bacterial adhesion in physiological environment and exhibit excellent antibacterial activity in infection environment. In vitro and in vivo experiments indicated that the PAA-co-PFDA/PHMB complex nanoparticle coated catheters exhibited excellent antibacterial activity and possessed good biocompatibility. This method is simple and scalable, which is important for future commercialization. The attractive multifunctional properties of the PAA-co-PFDA/PHMB complex nanoparticles, such as antifouling, antimicrobial, emission, and pH-responsive release character, have great potential application in a wide range of biomedical fields.


Asunto(s)
Antibacterianos/farmacología , Infecciones Relacionadas con Catéteres/prevención & control , Catéteres/microbiología , Polímeros de Fluorocarbono/síntesis química , Animales , Antibacterianos/química , Bacterias/efectos de los fármacos , Adhesión Bacteriana/efectos de los fármacos , Fenómenos Fisiológicos Bacterianos , Infecciones Relacionadas con Catéteres/microbiología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Femenino , Polímeros de Fluorocarbono/química , Humanos , Ratones , Ratones Endogámicos BALB C , Agua/química
18.
Biomater Sci ; 8(18): 5071-5087, 2020 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-32812545

RESUMEN

High-pressure torsion (HPT) can refine the microstructure and consequently modify the properties, such as mechanical and corrosion properties, of Mg and its alloys. Biodegradable magnesium materials alloyed with the essential elements of life, such as Ca and Sr, are a current research frontier. In this study, biodegradable ultrafine-grained pure Mg, Mg-Ca alloy, and Mg-Sr alloy were prepared using HPT processing. The microstructure, mechanical properties, biodegradable behaviors, and biocompatibility in vitro and in vivo of these materials were systematically investigated. Our results revealed that HPT pure Mg with a bimodal and ultrafine-grained microstructure showed higher mechanical strength, ductility, and degradation rate compared with the as-received materials. The good biocompatibility of HPT pure Mg was confirmed both in vitro and in vivo. The HPT Mg-Ca alloy and Mg-Sr alloy with homogeneous ultrafine-grained microstructures showed higher mechanical strength and lower degradation rate than their as-cast counterparts. The good biocompatibility of the HPT Mg-Ca alloy and Mg-Sr alloy was also revealed. All these findings indicate that HPT is an alternative avenue to fabricate biodegradable Mg-based materials.


Asunto(s)
Aleaciones , Magnesio , Materiales Biocompatibles , Corrosión , Ensayo de Materiales
19.
J Colloid Interface Sci ; 541: 461-469, 2019 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-30716656

RESUMEN

The diverse morphologies of aggregates formed by the self-assembly of block copolymers in selective solvents have attracted widespread attention, but the design of aggregate shapes is still limited owing to the thermodynamic favorability of sphere formation. In this paper, we report our discovery that polyhedral aggregates can be formed by the self-assembly of 1H,1H,2H,2H-perfluoro-1-dodecanol (PFD)-grafted amphiphilic polystyrene-b-poly(acrylic acid) (PS-b-PAA-g-PFD) copolymers in water at room temperature. It is determined that the crystallization of fluorocarbon side chains at the surface of PS-b-PAA-g-PFD aggregates induces the formation of a polyhedral shape. The morphology of aggregates can be controlled by the dialysis temperature, the grafting ratio of PFD in PS-b-PAA-g-PFD copolymers, and the initial copolymer concentration. The layers of polyhedral aggregates show excellent antibacterial adhesion properties. We anticipate that this method will expand the promise of self-assembly for the synthesis of a series of nonspherical micellar nanoparticles, which have promising applications in various fields.


Asunto(s)
Acrilatos/química , Antibacterianos/química , Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Micelas , Polímeros/química , Poliestirenos/química , Staphylococcus aureus/efectos de los fármacos , Nanopartículas/administración & dosificación , Nanopartículas/química , Propiedades de Superficie
20.
Biomater Sci ; 7(3): 951-962, 2019 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-30534762

RESUMEN

Near-infrared (NIR) light-induced imaging-guided cancer therapy has been studied extensively in recent years. Herein, we report a novel theranostic nanoplatform by modifying polyoxometalate (POM) nanoclusters onto mesoporous silica-coated upconversion nanoparticles (UCNPs), followed by loading doxorubicin (DOX) in the mesopores and coating a folate-chitosan shell onto the surface. In this nanoplatform, the core-shell structured UCNPs (NaYF4:Yb,Er@NaYF4:Yb,Nd) showed special upconverting luminescence (UCL) when irradiated with high-penetration 808 nm NIR light, and the doped Yb and Nd ions endowed the sample with CT imaging properties, thus achieving a dual-mode imaging function. Moreover, the simultaneously generated heat mediated by the 808 nm NIR light may coordinate with the chemotherapy generated from the released DOX to realize an efficient synergistic therapy, verified by diverse in vitro and in vivo assays. The coated folate-chitosan shell can target the platform to tumor tissues when it was transported in the blood vessels and accumulated in tumor sites via the enhanced permeability and retention effect (EPR). Due to the acidic and reductive microenvironment of the tumor, the DOX released quickly with the dissolved folate-chitosan shell, exhibiting obvious tumor microenvironment (TME) responsive properties. The smart imaging-guided therapeutic nanoplatform should be highly promising in TME responsive therapy.


Asunto(s)
Portadores de Fármacos/química , Nanopartículas/química , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Supervivencia Celular/efectos de los fármacos , Quitosano/química , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Femenino , Ácido Fólico/química , Células HeLa , Hemólisis/efectos de los fármacos , Humanos , Rayos Infrarrojos , Ratones , Microscopía Confocal , Nanopartículas/toxicidad , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Porosidad , Dióxido de Silicio/química , Tomografía Computarizada por Rayos X , Compuestos de Tungsteno/química
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