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Mitochondria, pivotal organelles crucial for energy generation, apoptosis regulation, and cellular metabolism, have spurred remarkable advancements in targeted material development. This review surveys recent breakthroughs in targeted mitochondrial nanomaterials, illuminating their potential in drug delivery, disease management, and biomedical imaging. This review approaches from various application perspectives, introducing the specific applications of mitochondria-targeted materials in cancer treatment, probes and imaging, and diseases treated with mitochondria as a therapeutic target. Addressing extant challenges and elucidating potential therapeutic mechanisms, it also outlines future development trajectories and obstacles. By comprehensively exploring the diverse applications of targeted mitochondrial nanomaterials, this review aims to catalyze innovative treatment modalities and diagnostic approaches in medical research. STATEMENT OF SIGNIFICANCE: This review presents the latest advancements in mitochondria-targeted nanomaterials for biomedical applications, covering diverse fields such as cancer therapy, bioprobes, imaging, and the treatment of various systemic diseases. The novelty and significance of this work lie in its systematic analysis of the intricate relationship between mitochondria and different diseases, as well as the ingenious design strategies employed to harness the therapeutic potential of nanomaterials. By providing crucial insights into the development of mitochondria-targeted nanomaterials and their applications, this review offers a valuable resource for researchers working on innovative treatment modalities and diagnostic approaches. The scientific impact and interest to the readership lie in the identification of promising avenues for future research and the potential for clinical translation of these cutting-edge technologies.
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The development of a natural, additive-free, absorbable sponge with procoagulant activity for noncompressible hemostasis remains a challenging task. In this study, we extracted high molecular weight keratin (HK) from human hair and transformed it into a hemostatic sponge with a well-interconnected pore structure using a foaming technique, freeze-drying, and oxidation cross-linking. By controlling the cross-linking degree, the resulting sponge demonstrated excellent liquid absorption ability, shape recovery characteristics, and robust mechanical properties. The HK10 sponge exhibited rapid liquid absorption, expanding up to 600% within 5 s. Moreover, the HK sponge showed superior platelet activation and blood cell adhesion capabilities. In SD rat liver defect models, the sponges demonstrated excellent hemostatic performance by sealing the wound and expediting coagulation, reducing the hemostatic time from 825 to 297 s. Furthermore, HK sponges have excellent biosafety, positioning them as a promising absorbable sponge with the potential for the treatment of noncompressible hemostasis.
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Hemostasia , Hemostáticos , Queratinas , Ratos Sprague-Dawley , Animais , Ratos , Queratinas/química , Queratinas/farmacologia , Humanos , Hemostasia/efeitos dos fármacos , Hemostáticos/química , Hemostáticos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Masculino , Ativação Plaquetária/efeitos dos fármacosAssuntos
Bactérias , Humanos , Bactérias/imunologia , Bactérias/genética , Simbiose/imunologia , Simbiose/genética , AnimaisRESUMO
There is an unmet need for easy-to-visualize drug carriers that can deliver therapeutic cargoes deep into solid tumors. Herein, we report the preparation of ultrasmall luminescent imine-based lanthanide nanocages, Eu60 and Tb60 (collectively Ln60 ), designed to encapsulate anticancer chemotherapeutics for tumor therapy. The as-prepared nanocages possess large cavities suitable for the encapsulation of doxorubicin (DOX), yielding DOX@Ln60 nanocages with diameters around 5â nm. DOX@Ln60 are efficiently internalized by breast cancer cells, allowing the cells to be visualized via the intrinsic luminescent property of Ln(III). Once internalized, the acidic intracellular microenvironment promotes imine bond cleavage and the release of the loaded DOX. DOX@Ln60 inhibits DNA replication and triggers tumor cell apoptosis. In a murine triple negative breast cancer (TNBC) model, DOX@Ln60 was found to inhibit tumor growth with negligible side effects on normal tissues. It proved more effective than various controls, including DOX and Ln60 . The present nanocages thus point the way to the development of precise nanomedicines for tumor imaging and therapy.
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Elementos da Série dos Lantanídeos , Nanopartículas , Animais , Camundongos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Iminas , Nanopartículas/químicaRESUMO
Dry eye disease (DED) is currently the most prevalent condition seen in ophthalmology outpatient clinics, representing a significant public health issue. The onset and progression of DED are closely associated with oxidative stress-induced inflammation and damage. To address this, an aldehyde-functionalized F127 (AF127) hydrogel eye drop delivering multifunctional antioxidant Cu2-xSe nanoparticles (Cu2-xSe NPs) was designed. The research findings revealed that the Cu2-xSe nanoparticles exhibit unexpected capabilities in acting as superoxide dismutase and glutathione peroxidase. Additionally, Cu2-xSe NPs possess remarkable efficacy in scavenging reactive oxygen species (ROS) and mitigating oxidative damage. Cu2-xSe NPs displayed promising therapeutic effects in a mouse model of dry eye. Detailed investigation revealed that the nanoparticles exert antioxidant, anti-apoptotic, and inflammation-mitigating effects by modulating the NRF2 and p38 MAPK signalling pathways. The AF127 hydrogel eye drops exhibit good adherence to the ocular surface through the formation of Schiff-base bonds. These findings suggest that incorporating antioxidant Cu2-xSe nanoparticles into a tissue-adhesive hydrogel could present a highly effective therapeutic strategy for treating dry eye disease and other disorders associated with reactive oxygen species. STATEMENT OF SIGNIFICANCE: A new formulation for therapeutic eye drops to be used in the treatment of dry eye disease (DED) was developed. The formulation combines copper-selenium nanoparticles (Cu2-xSe NPs) with aldehyde-functionalized Pluronic F127 (AF127). This is the first study to directly examine the effects of Cu2-xSe NPs in ophthalmology. The NPs exhibited antioxidant capabilities and enzyme-like properties. They effectively eliminated reactive oxygen species (ROS) and inhibited apoptosis through the NRF2 and p38 MAPK signalling pathways. Additionally, the AF127 hydrogel enhanced tissue adhesion by forming Schiff-base links. In mouse model of DED, the Cu2-xSe NPs@AF127 eye drops demonstrated remarkable efficacy in alleviating symptoms of DED. These findings indicate the potential of Cu2-xSe NPs as a readily available and user-friendly medication for the management of DED.
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Síndromes do Olho Seco , Nanopartículas , Polietilenos , Polipropilenos , Camundongos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Cobre/farmacologia , Cobre/química , Espécies Reativas de Oxigênio , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Fator 2 Relacionado a NF-E2/uso terapêutico , Nanopartículas/uso terapêutico , Nanopartículas/química , Inflamação/tratamento farmacológico , Síndromes do Olho Seco/tratamento farmacológico , Soluções Oftálmicas/farmacologia , Aldeídos , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
Ionic substitution can effectively activate the surface of hydroxyapatite (HA) for bone repair and regeneration processes. Therefore in this study, magnesium (Mg)-, zinc (Zn)-, and Mg/Zn-codoped HA was prepared by a hydrothermal method. The results of experimental and first-principles calculations verify the existence of Mg and Zn ions in the HA structure by altering cell parameters, crystallinity, and particle size. The results also showed that Mg and Zn are actively accommodated at the Ca(1) and Ca(2) positions, which not only inhibit HA formation but also promote calcium-deficient HA, and when the codoping content increased to 10%Mg and 10%Zn, the HA transformed completely to the whitlockite phase. Furthermore, the impact of codoping on biocompatibility was examined by employing MC3T3 cells. The in vitro study revealed that 5%Mg and 5%Zn single and -codoped HA promoted the proliferation of MC3T3 cells and 5%Mg-doped and -codoped HA stimulated MC3T3 cell differentiation, while 5%Zn-doped and -codoped HA revealed worthy antibacterial properties. Overall, the obtained results demonstrate that cosubstituted HA (5%Mg and 5%Zn) is promising, which not only eradicates bacteria (Escherichia coli and Staphylococcus aureus) but also induces bone regeneration. These findings suggest that 5%Mg and 5%Zn binary-substituted HA is a very promising biomaterial for hard tissue scaffolds and bone repair.
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Durapatita , Zinco , Durapatita/farmacologia , Durapatita/química , Zinco/farmacologia , Zinco/química , Magnésio/farmacologia , Magnésio/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Large size bone defects affect human health and remain a worldwide health problem that needs to be solved immediately. 3D printing technology has attracted substantial attention for preparing penetrable multifunctional scaffolds to promote bone reconditioning and regeneration. Inspired by the spongy structure of natural bone, novel porous degradable scaffolds have been printed using polymerization of lactide and caprolactone (PLCL) and bioactive glass 45S5 (BG), and polydopamine (PDA) was used to decorate the PLCL/BG scaffolds. The physicochemical properties of the PLCL/BG and PLCL/BG/PDA scaffolds were measured, and their osteogenic and angiogenic effects were characterized through a series of experiments both in vitro and in vivo. The results show that the PLCL/BG2/PDA scaffold possessed a good compression modulus and brilliant hydrophilicity. The proliferation, adhesion and osteogenesis of hBMSCs were improved in the PDA coating groups, which exhibited the best performance. The results of the SD rat cranium defect model indicate that PLCL/BG2/PDA obviously promoted osteointegration, which was further confirmed through immunohistochemical staining. Therefore, PDA decoration and the sustained release of bioactive ions (Ca, Si, P) from BG in the 3D-printed PLCL/BG2/PDA scaffold could improve surface bioactivity and promote better osteogenesis and angiogenesis, which may provide a valuable basis for customized implants in extensive bone defect repair applications.
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Pressure injuries (PIs) are localized tissue damage resulting from prolonged compression or shear forces on the skin or underlying tissue, or both. Different stages of PIs share common features include intense oxidative stress, abnormal inflammatory response, cell death, and subdued tissue remodeling. Despite various clinical interventions, stage 1 or stage 2 PIs are hard to monitor for the changes of skin or identify from other disease, whereas stage 3 or stage 4 PIs are challenging to heal, painful, expensive to manage, and have a negative impact on quality of life. Here, we review the underlying pathogenesis and the current advances of biochemicals in PIs. We first discuss the crucial events involved in the pathogenesis of PIs and key biochemical pathways lead to wound delay. Then, we examine the recent progress of biomaterials-assisted wound prevention and healing and their prospects.
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Drug combination provides an efficient pathway to combat drug resistance in bacteria and bacterial biofilms. However, the facile methodology to construct the drug combinations and their applications in nanocomposites is still lacking. Here the two-tailed antimicrobial amphiphiles (T2 A2 ) composed of nitric oxide (NO)-donor (diethylenetriamine NONOate, DN) and various natural aldehydes are reported. T2 A2 self-assemble into nanoparticles due to their amphiphilic nature, with remarkably low critical aggregation concentration. The representative cinnamaldehyde (Cin)-derived T2 A2 (Cin-T2 A2 ) assemblies demonstrate excellent bactericidal efficacy, notably higher than free Cin and free DN. Cin-T2 A2 assemblies kill multidrug-resistant staphylococci and eradicate their biofilms via multiple mechanisms, as proved by mechanism studies, molecular dynamics simulations, proteomics, and metabolomics. Furthermore, Cin-T2 A2 assemblies rapidly eradicate bacteria and alleviate inflammation in the subsequent murine infection models. Together, the Cin-T2 A2 assemblies may provide an efficient, non-antibiotic alternative in combating the ever-increasing threat of drug-resistant bacteria and their biofilms.
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Anti-Infecciosos , Nanopartículas , Camundongos , Animais , Bactérias , Antibacterianos/farmacologia , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
Purpose: This study aimed to explore the possibility of utilizing hepatitis B core protein (HBc) virus-like particles (VLPs) encapsulate doxorubicin (Dox) to reduce the adverse effect caused by its off-target and toxic side effect. Methods: Here, a triple-negative breast cancer (TNBC) tumor-targeting GE11-HBc VLP was constructed through genetic engineering. The GE11 peptide, a 12-amino-acid peptide targeting epidermal growth factor receptor (EGFR), was inserted into the surface protein loops of VLPs. The Dox was loaded into HBc VLPs by a thermal-triggered encapsulation strategy. The in vitro release, cytotoxicity, and cellular uptake of TNBC tumor-targeting GE11-HBc VLPs was then evaluated. Results: These VLPs possessed excellent stability, DOX loading efficiency, and preferentially released drug payload at high GSH levels. The insertion of GE11 targeting peptide caused improved cellular uptake and enhanced cell viability inhibitory in EGFR high-expressed TNBC cells. Conclusion: Together, these results highlight DOX-loaded, EGFR-targeted VLPs as a potentially useful therapeutic choice for EGFR-overexpressing TNBC.
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An ideal bone regenerative scaffold is expected to possess architectural characteristics that mimic the bone tissue, osteoconductive properties, and osteoinductive functionality. Key challenges to creating a scaffold with these ideal characteristics simultaneously are the selection of appropriate processing methods and biocompatible materials. Herein, human hair keratin is proposed as an organic binder for the simultaneous incorporation of bone's major inorganic component, hydroxyapatite and bone's growth factor, recombinant human bone morphogenetic protein 2 (rhBMP2) to enable both osteoconductive and osteoinductive characteristics in the creation of bone scaffolds. Furthermore, a freeze-casting method is selected to fabricate this rhBMP2-incorporated keratin/hydroxyapatite (KHA) scaffold with aligned lamellar pores to guide and promote bone regeneration. The aligned KHA scaffolds display better mechanical properties, sustained rhBMP2 release, good cell compliance, and 3D cellular infiltration. Implantation of KHA scaffolds in vivo reveals that scaffolds with aligned pores effectively accelerate the healing process of bone defects compared to scaffolds with random pores. This work indicates the distinctive potential of freeze-casted rhBMP-2 incorporated KHA scaffolds for bone regeneration.
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Durapatita , Alicerces Teciduais , Humanos , Durapatita/farmacologia , Queratinas , Proteína Morfogenética Óssea 2/farmacologia , Regeneração Óssea , Crânio , OsteogêneseRESUMO
Hydrogel-based conductive materials for smart wearable devices have attracted increasing attention due to their excellent flexibility, versatility, and outstanding biocompatibility. This review presents the recent advances in multifunctional conductive hydrogels for electronic devices. First, conductive hydrogels with different components are discussed, including pure single network hydrogels based on conductive polymers, single network hydrogels with additional conductive additives (i.e., nanoparticles, nanowires, and nanosheets), double network hydrogels based on conductive polymers, and double network hydrogels with additional conductive additives. Second, conductive hydrogels with a variety of functionalities, including self-healing, super toughness, self-growing, adhesive, anti-swelling, antibacterial, structural color, hydrophobic, anti-freezing, shape memory and external stimulus responsiveness are introduced in detail. Third, the applications of hydrogels in flexible devices are illustrated (i.e., strain sensors, supercapacitors, touch panels, triboelectric nanogenerator, bioelectronic devices, and robot). Next, the current challenges facing hydrogels are summarized. Finally, an imaginative but reasonable outlook is given, which aims to drive further development in the future.
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The development of biocompatible materials with desired functions is essential for tissue engineering and biomedical applications. Hydrogels prepared from these materials represent an important class of soft matter for mimicking extracellular environments. In particular, dynamic hydrogels with responsiveness to environments are quite appealing because they can match the dynamics of biological processes. Among the external stimuli that can trigger responsive hydrogels, light is considered as a clean stimulus with high spatiotemporal resolution, complete bioorthogonality, and fine tunability regarding its wavelength and intensity. Therefore, photoresponsiveness has been broadly encoded in hydrogels for biological applications. Moreover, light can be used to initiate gelation during the fabrication of biocompatible hydrogels. Here, we present a critical review of light manipulation tools for the fabrication of hydrogels and for the regulation of physicochemical properties and functions of photoresponsive hydrogels. The materials, photo-initiated chemical reactions, and new prospects for light-induced gelation are introduced in the former part, while mechanisms to render hydrogels photoresponsive and their biological applications are discussed in the latter part. Subsequently, the challenges and potential research directions in this area are discussed, followed by a brief conclusion. STATEMENT OF SIGNIFICANCE: Hydrogels play a vital role in the field of biomaterials owing to their water retention ability and biocompatibility. However, static hydrogels cannot meet the dynamic requirements of the biomedical field. As a stimulus with high spatiotemporal resolution, light is an ideal tool for both the fabrication and operation of hydrogels. In this review, light-induced hydrogelation and photoresponsive hydrogels are discussed in detail, and new prospects and emerging biological applications are described. To inspire more research studies in this promising area, the challenges and possible solutions are also presented.
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Materiais Biocompatíveis , Hidrogéis , Engenharia TecidualRESUMO
Finding a suitable biomaterial for scaffolding in cartilage tissue engineering has proved to be far from trivial. Nonetheless, it is clear that biomimetic approaches based on gelatin (Gel) and hyaluronic acid (HA) have particular promise. Herein, a set of formulations consisting of photo-polymerizable Gel; photo-polymerizable HA, and allogenic decellularized cartilage matrix (DCM), is synthesized and characterized. The novelty of this study lies particularly in the choice of DCM, which was harvested from an abnormal porcine with α-1,3-galactose gene knockout. The hybrid hydrogels were prepared and studied extensively, by spectroscopic methods, for their capacity to imbibe water, for their behavior under compression, and to characterize microstructure. Subsequently, the effects of the hydrogels on contacting cells (in vitro) were studied, i.e., cytotoxicity, morphology, and differentiation through monitoring the specific markers ACAN, Sox9, Coll2, and Col2α1, hypertrophy through monitoring the specific markers alkaline phosphatase (ALP) and Col 10A1. In vivo performance of the hydrogels was assessed in a rat knee cartilage defect model. The new data expand our understanding of hydrogels built of Gel and HA, since they reveal that a significant augmenting role can be played by DCM. The data strongly suggest that further experimentation in larger cartilage-defect animal models is worthwhile and has potential utility for tissue engineering and regenerative medicine.
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MicroRNAs play an irreplaceable role in gene expression regulation. Upregulation of several miRNAs increases the risk of invasion and metastasis of breast cancer cells. An oncogenic miRNA, miR-21, is highly expressed in triple-negative breast cancer (TNBC) and is associated with tumor proliferation, invasion, carcinogenesis, prognosis, and therapeutic resistance. However, targeted delivery of therapeutic anti-miRNAs into cancer cells remains challenging, especially for TNBC. In this study, we report the application of an RNA nanotechnology-based platform for the targeted delivery of anti-miR-21 by epidermal growth factor receptor (EGFR) aptamer in vitro to TNBC and chemical-resistant breast cancer cells. RNA nanoparticles reduced cell viability and sensitized breast cancer cells to doxorubicin (DOX) treatment in vitro. Inhibition of miR-21 by RNA nanoparticles suppressed TNBC cell invasion, migration, and colony formation. The results indicate the potential application of nanotechnology-based delivery platforms in clinical anti-cancer therapeutics.
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Aptâmeros de Nucleotídeos/genética , Aptâmeros de Nucleotídeos/uso terapêutico , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Aptâmeros de Nucleotídeos/administração & dosagem , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Terapia de Alvo Molecular/métodos , Nanopartículas/administração & dosagem , Nanopartículas/uso terapêutico , Nanotecnologia , Invasividade Neoplásica/genética , Neoplasias de Mama Triplo Negativas/patologia , Ensaio Tumoral de Célula-TroncoRESUMO
Temporal lobe epilepsy (TLE) is a chronic disease of the nervous system, associated with increased proliferation in the hippocampus. Urothcarcinoma associated 1 (UCA1) is a long long non-coding RNA that was shown to regulate proliferation and differentiation of neural progenitors in vitro. We hypothesised that TLE-associated abnormal proliferation is a consequence of the downregulation of UCA1. This hypothesis was tested in mice with kainic acid (KA)-induced seizures, and then the potential mechanism was explored in vitro and in vivo. Result showed that the expression of UCA1 and Secreted Frizzled Related Protein 1 (SFRP1) were significantly reduced in hippocampal tissues of epileptic mice, while miR-375 was increased compared with the control group. Pearson correlation analysis showed that UCA1 was positively correlated with SFRP1, while miR-375 was negatively correlated with UCA1 and SFRP1. Besides, UCA1 was overexpressed in mice and the overexpression of UCA1 significantly reversed the abnormal proliferation of hippocampal neurons in epilepsy mice. In vitro Luciferase assay showed that UCA1 and Sfrp1 are both the targets of miR-375, and UCA1 promotes the expression of Sfrp1 by competitively adsorbing miR-375, thereby inhibiting the activation of the WNT/ß-catenin pathway. The inactivation of the WNT/ß-catenin pathway prevented the abnormal proliferation of neural progenitors in the epileptic hippocampus. In conclusion, our findings provide a theoretical basis for the clinical application of UCA1.
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Epilepsia/genética , Hipocampo/efeitos dos fármacos , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Neurogênese/efeitos dos fármacos , RNA Longo não Codificante/genética , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Proliferação de Células/genética , Epilepsia/metabolismo , Vetores Genéticos/farmacologia , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ácido Caínico/efeitos adversos , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Neurogênese/genética , Via de Sinalização Wnt/genéticaRESUMO
Xenogeneic bones are potential templates for bone regeneration. In this study, decellularized porcine bone powder with attenuated immunogenicity was incorporated into a photocurable hydrogel, gelatin methacryloyl (GelMA), to obtain scaffolds with good mechanical properties for bone tissue engineering. The decellularized bone powder (DCB)-GelMA hybrid scaffolds had higher compressive strength and stiffness values when the DCB content was increased. In vitro evaluations revealed the biocompatibility of these scaffolds. The scaffolds could induce human bone marrow mesenchymal stem cells (hMSCs) to undergo osteogenic differentiation even in the absence of an induction medium. The efficiency of the scaffolds for bone regeneration applications was further evaluated using an in vivo cranial bone defect model in rats. Micro-CT images showed that the hybrid scaffolds with 20% DCB content had the best effect in promoting new bone regeneration. Thus, it was concluded that the DCB-GelMA hybrid scaffolds have high potential in bone tissue engineering applications.
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Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiologia , Hidrogéis/química , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Osso e Ossos/citologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Força Compressiva , Gelatina/química , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Metacrilatos/química , Osteogênese/efeitos dos fármacos , SuínosRESUMO
BACKGROUND: To date, triple-negative breast cancer (TNBC) treatment options are limited because of the loss of target receptors and, as a result, are only managed with chemotherapy. What is worse is that TNBC is frequently developing resistance to chemotherapy. By using small interfering RNA (siRNA)-based therapeutics, our recent work demonstrated X-box-binding protein 1 (XBP1) was linked to human epidermal growth factor receptor 2 positive (HER2+) breast cancer development and chemoresistance. Given the instability, off-target effects, net negative charge, and hydrophobicity of siRNA in vivo utilization and clinical transformation, its use in treatment is hampered. Thus, the development of a siRNA-based drug delivery system (DDS) with ultra-stability and specificity is necessary to address the predicament of siRNA delivery. RESULTS: Here, we assembled RNase resistant RNA nanoparticles (NPs) based on the 3WJ structure from Phi29 DNA packaging motor. To improved targeted therapy and sensitize TNBC to chemotherapy, the RNA NPs were equipped with an epidermal growth factor receptor (EGFR) targeting aptamer and XBP1 siRNA. We found our RNA NPs could deplete XBP1 expression and suppress tumor growth after intravenous administration. Meanwhile, RNA NPs treatment could promote sensitization to chemotherapy and impede angiogenesis in vivo. CONCLUSIONS: The results further demonstrate that our RNA NPs could serve as an effective and promising platform not only for siRNA delivery but also for chemotherapy-resistant TNBC therapy.
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Bacteriófagos/genética , Sistemas de Liberação de Medicamentos/métodos , RNA Interferente Pequeno/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Receptores ErbB/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Nus , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A novel series of composite hydrogels, built from the three components 1), hyaluronic acid methacryloyl (HAMA); 2), gelatin methacryloyl (GelMA), and 3), extracellular cartilage matrix (ECM), was prepared and studied regarding the possible utility in the surgical repair of damaged (perforated) tympanic membrane (TM). Noteworthy is component 3), which was harvested from the ribs of α-1,3-galactosidyltransferase-knockout (α-1,3 GalT-KO) pigs. The absence of α-1,3-galactosyl glycoprotein is hypothesized to prevent rejection due to foreign-body immunogenicity. The composite hydrogels were characterized by various aspects, using a variety of physicochemical techniques: aqueous swelling, structural degradation, behavior under compression, and morphology, e.g., in vitro biocompatibility was assessed by the CCK-8 and live-dead assays and through cytoskeleton staining/microscopy. Alcian blue staining and real-time PCR (RT-PCR) were performed to examine the chondrogenic induction potential of the hydrogels. Moreover, a rat TM defect model was used to evaluate the in vivo performance of the hydrogels in this particular application. Taken together, the results from this study are surprising and promising. Much further development work will be required to make the material ready for surgical use.