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Nanoparticle-based systems are extensively investigated for drug delivery. Among others, with superior biocompatibility and enhanced targeting capacity, albumin appears to be a promising carrier for drug delivery. Albumin nanoparticles are highly favored in many disease therapies, as they have the proper chemical groups for modification, cell-binding sites for cell adhesion, and affinity to protein drugs for nanocomplex generation. Herein, this review summarizes the recent fabrication techniques, modification strategies, and application of albumin nanoparticles. We first discuss various albumin nanoparticle fabrication methods, from both pros and cons. Then, we provide a comprehensive introduction to the modification section, including organic albumin nanoparticles, metal albumin nanoparticles, inorganic albumin nanoparticles, and albumin nanoparticle-based hybrids. We finally bring further perspectives on albumin nanoparticles used for various critical diseases.
Albumin appears to be a promising carrier for drug delivery with superior biocompatibility and enhanced targeting capacity. This review focuses on the importance of albumin nanoparticles in drug delivery and concludes the recent fabrication techniques to prepare albumin nanoparticles, the modification strategies to require functional albumin nanoparticles, and critical applications of albumin nanoparticles in various diseases. The aim of this review is to help readers understand the significant potential of albumin nanoparticles in drug delivery.
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Albúminas , Nanopartículas , Humanos , Albúminas/química , Albúminas/administración & dosificación , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Animales , Portadores de Fármacos/química , Sistema de Administración de Fármacos con Nanopartículas/químicaRESUMEN
Doxorubicin (DOX) has been an effective antitumor agent for human liver cancer cells; however, an overdose might lead to major side effects appearing in clinical applications. In this work, we present a strategy of combining DOX and blue light (BL) irradiation for the antitumor treatment of HepG2 cells (one typical human liver cancer cell line). It is demonstrated that synergetic DOX and BL can significantly reduce cell proliferation and increase the apoptotic rate of HepG2 cells in comparison to individual DOX treatment. The additional BL irradiation is further helpful for enhancing the inhibition of cell migration and invasion. Analyses of reactive oxygen species (ROS) level and Western blotting reveal that the strategy results in more ROS accumulation, mitochondrial damage, and the upregulation of proapoptotic protein (Bcl-2) and downregulation of antiapoptotic protein (Bax). In addition to the improved therapeutic effect, the non-contact BL irradiation is greatly helpful for reducing the dosage of DOX, and subsequently reduces the side effects caused by the DOX drug. These findings offer a novel perspective for the therapeutic approach toward liver cancer with high efficiency and reduced side effects.
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Apoptosis , Movimiento Celular , Proliferación Celular , Doxorrubicina , Luz , Neoplasias Hepáticas , Especies Reactivas de Oxígeno , Doxorrubicina/farmacología , Humanos , Células Hep G2 , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Movimiento Celular/efectos de los fármacos , Movimiento Celular/efectos de la radiación , Luz AzulRESUMEN
Ginsenoside (GS), one of the main active components in ginseng, can enhance insulin sensitivity, improve the function of islet ß cells, and reduce cell apoptosis in the treatment of diabetes. However, the drawbacks of high lipid solubility, poor water solubility, and low oral availability in Ginsenoside Rg3 (G-Rg3) seriously limit further application of GS. In this work, a G-Rg3 PEGylated long-circulating liposome (PEG-L-Rg3) is designed and developed to improve symptoms in type 2 diabetic mice. The as-prepared PEG-L-Rg3 with a spherical structure shows a particle size of â¼ 140.5 ± 1.4 nm, the zeta potential of -0.10 ± 0.05 mV, and a high encapsulation rate of 99.8 %. Notably, in vivo experimental results demonstrate that PEG-L-Rg3 exhibits efficient ability to improve body weight and food intake in streptozotocin-induced type 2 diabetic mice. Moreover, PEG-L-Rg3 also enhances fasting insulin (FINS) and insulin sensitivity index (ISI). In addition, the glucose tolerance of mice is significantly improved after the treatment of PEG-L-Rg3, indicating that PEG-L-Rg3 can be a potential drug for the treatment of type 2 diabetes, which provides a new way for the treatment of type 2 diabetes using ginsenosides.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Ginsenósidos , Hiperglucemia , Resistencia a la Insulina , Liposomas , Polietilenglicoles , Animales , Ginsenósidos/administración & dosificación , Ginsenósidos/farmacología , Ginsenósidos/química , Ratones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológico , Polietilenglicoles/química , Masculino , Hiperglucemia/tratamiento farmacológico , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Estreptozocina , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Insulina , Tamaño de la PartículaRESUMEN
Human growth hormone (hGH) has emerged as a promising therapeutic agent to prevent and treat skin photoaging. However, the success of hGH therapy largely lies in the availability of an optimal delivery system that enables the efficient delivery of hGH to the dermal layer of the skin. Here, we report a delivery system of hyaluronic acid/liposome-gel-encapsulated hGH (HA/HL-Gel) that can transdermally deliver hGH into the skin for hGH-based photoaging therapy through the upregulation of collagen type I (collagen-I). Specifically, hGH-liposomes were prepared by ethanol injection and then modified with HA to achieve specific targeting. The best formulation of HA/hGH-liposomes (HA/HL) had a high encapsulation efficiency (about 20%), with a size of 180 ± 1.2 nm. The optimized HA/HL was further incorporated into the carbomer gel to form an HA/HL-Gel. The biological activity of HA/HL on human dermal fibroblasts (HDFs) was confirmed by the elevated expression level of collagen-I through the enhanced local formation of insulin-like growth factor-1 (IGF-1) in the photoaging model. Moreover, HA/HL-Gel reduced ultraviolet (UV)-induced erythema and wrinkle formation. Meanwhile, immunohistochemical staining further showed higher levels of collagen-I in the HA/HL-Gel group compared to other groups tested. Taken together, these results demonstrate that HA/HL-Gel treatment could significantly ameliorate skin photoaging and thus may be used as a clinical potential for antiaging therapy.
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Hormona de Crecimiento Humana , Liposomas , Envejecimiento de la Piel , Envejecimiento de la Piel/efectos de los fármacos , Humanos , Liposomas/química , Hormona de Crecimiento Humana/administración & dosificación , Hormona de Crecimiento Humana/química , Administración Cutánea , Geles/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Tamaño de la Partícula , Ensayo de Materiales , Animales , Proteínas Recombinantes/administración & dosificación , Piel/metabolismo , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Rayos Ultravioleta , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismoRESUMEN
The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach in which a combination of nano- and milli-second pulses produces large amounts of IFN-γ mRNA-loaded sEVs with CD64 overexpressed on their surface. The CD64 molecule serves as an adaptor to dock targeting ligands, such as anti-CD71 and anti-programmed cell death-ligand 1 (PD-L1) antibodies. The resulting immunogenic sEVs (imsEV) preferentially target glioblastoma cells and generate potent antitumour activities in vivo, including against tumours intrinsically resistant to immunotherapy. Together, these results provide an adaptive approach to engineering mRNA-loaded sEVs with targeting functionality and pave the way for their adoption in cancer immunotherapy applications.
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Vesículas Extracelulares , Glioblastoma , Humanos , ARN Mensajero/genética , Inmunoterapia/métodos , Vesículas Extracelulares/genética , ElectroporaciónRESUMEN
In recent years, owing to the miniaturization of the fluidic environment, microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems (NDDSs) production processes. Compared with traditional methods, microfluidics improves the controllability and uniformity of NDDSs. The fast mixing and laminar flow properties achieved in the microchannels can tune the physicochemical properties of NDDSs, including particle size, distribution and morphology, resulting in narrow particle size distribution and high drug-loading capacity. The success of lipid nanoparticles encapsulated mRNA vaccines against coronavirus disease 2019 by microfluidics also confirmed its feasibility for scaling up the preparation of NDDSs via parallelization or numbering-up. In this review, we provide a comprehensive summary of microfluidics-based NDDSs, including the fundamentals of microfluidics, microfluidic synthesis of NDDSs, and their industrialization. The challenges of microfluidics-based NDDSs in the current status and the prospects for future development are also discussed. We believe that this review will provide good guidance for microfluidics-based NDDSs.
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Intracellular redox imbalance, achieved by exploiting the tumor microenvironment (TME), has emerged as a promising strategy for cancer therapy. In this study, we developed a multifunctional nanoadjuvant, termed GITFe/Z-HA, by modified a metal-organic backbone Fe/ZIF-8 with hyaluronic acid (HA) targeting. The nanocarriers were loaded with glucose oxidase (Gox), neoindocyanine green (IR820) and tilazamine (TPZ). This design aimed to achieve a cascade reaction within tumor cells, mediated by Gox, Fe3+, and IR820, which consumes intrinsic glucose and oxygen, leading to an elevated production of reactive oxygen species (ROS). This cascade reaction creates a hypoxic environment conducive for TPZ to exert its therapeutic action. Consequently, the combination of photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy demonstrates a good synergistic effect. Moreover, the imbalanced ROS/glutathione (GSH) induced by this treatment approach, along with PTT, promote immunogenic cell death (ICD). This ICD triggers the release of damage-related molecular patterns and CD8+ lymphocyte infiltration sensitizes the immune checkpoint blockade (αPD-L1) response, thereby eliciting a systemic anti-tumor immune response. Collectively, this comprehensive treatment regimen, driven by environmentally stimulated multiple pathways, overcomes the limitations of single therapeutic modalities, thereby improving tumor outcomes. Additionally, these findings provide valuable insights for strategies aimed at modulating the tumor immune microenvironment.
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Ginsenoside compound K (GCK) can efficiently treat rheumatoid arthritis (RA) due to its immune and anti-inflammatory functions. However, GCK exists some shortcomings such as poor aqueous solubility, low permeability to the intestinal cell membrane, and serious P-gp efflux, thus limiting its application. In order to solve these problems, a folic acid-targeted drug delivery system based on liposomes (FA-LP-GCK) was developed. The prepared FA-LP-GCK had a uniform size distribution and spherical structure, the particle size was 249.13 ± 1.40 nm. Meanwhile, they had high encapsulation efficiency (93.33 ± 0.05 %). FA-LP-GCK also presented good stability in artificial gastric juice, so they can be absorbed into the intestine and enter the blood circulation. The activated RAW 264.7 cells were chosen to evaluate the cytotoxicity and cellular uptake capacity of FA-LP-GCK. FA-LP-GCK showed stronger growth inhibition and cellular uptake ability against activated macrophages. Finally, the efficacy of FA-LP-GCK in vivo was evaluated in the adjuvant arthritis rat model. The results showed that FA-LP-GCK can significantly reduce joint swelling. Furthermore, it can significantly inhibit the expression of pro-inflammatory cytokines and improve synovial hyperplasia of joints and pathological changes in the spleen. Therefore, FA-LP-GCK may be a potential therapeutic approach for RA.
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Artritis Reumatoide , Ginsenósidos , Ratas , Animales , Liposomas/uso terapéutico , Sistemas de Liberación de Medicamentos , Ginsenósidos/farmacología , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Ácido Fólico/metabolismoRESUMEN
Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8+ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.
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Blue light (BL) irradiation has been a potentially efficient treatment for many kinds of tumors. In this study, a BL irradiation (centered at 453 nm in wavelength) was proposed to treat the common human liver cancer cell lines of SMMC-7721 and HepG2, examined by means of flow cytometry, western blot, fluorescence microscope assay. In comparison to control groups, the apoptosis and proliferation inhibition of both BL-treated cells are expressively enhanced by mitochondrial apoptosis. The mechanism of apoptosis is related to the more production of reactive oxygen species (ROS) induced by BL and the corresponding changes in the expression of apoptosis-related Bcl-2, Bax and Bad proteins. In addition, the migration rate of the cancer cells could be reduced after BL irradiation. These results demonstrate that introducing BL irradiation is helpful to establish an effective and low toxicity strategy for the clinical treatment of liver tumors.
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Apoptosis , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Luz , Línea Celular Tumoral , Proliferación Celular , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Tumor drug resistance has long been a major challenge in medical oncology. Ferroptosis is a form of regulated cell death with promising clinical applications. However, the efficacy of ferroptosis-inducing agents is often limited by endogenous factors when used alone, and thus, synergistic therapy offers a promising strategy to address this issue. In this study, we developed an iron-doped metal-organic framework (MOF), Fe/ZIF-8, loaded with glucose oxidase (Gox), l-arginine (l-arg), and adriamycin hydrochloride (Dox). The folic acid (FA)-targeted ZIF-8 (GLDFe/Z-FA) prepared was shown to be a multifunctional nanoparticle based on endogenous hydrogen peroxide (H2O2) and glucose, which trigger adaptive cellular responses in cancer cells. The intracellular glucose level and adenosine-triphosphate (ATP) content decreased, indicating that GLDFe/Z-FA reduced the glucose metabolic rate and induced tumor starvation. And the generated â¢OH and H2O2 induced reactive oxygen species (ROS) overload to implement chemodynamic therapy (CDT). ROS catalyzed l-arg released from GLDFe/Z-FA to release nitric oxide (NO), which inhibited P-glycoprotein expression, prevented Dox efflux, and accumulated intracellular content of Dox to enhance cytotoxicity. GLDFe/Z-FA also catalyzed glutathione degradation, which further disrupted intracellular redox homeostasis, enhanced CDT, and induced cell death. It was shown to follow the ferroptosis pathway and strongly inhibited tumor proliferation both in vitro and in vivo. These findings demonstrate that GLDFe/Z-FA effectively inhibits tumor proliferation, highlighting its potential as a viable therapeutic approach to suppress cancer progression.
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Nanopartículas , Neoplasias , Humanos , Óxido Nítrico , Resistencia a Múltiples Medicamentos , Peróxido de Hidrógeno , Especies Reactivas de Oxígeno , Resistencia a Antineoplásicos , Neoplasias/tratamiento farmacológico , Arginina , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Cancer remains a severe threat to human health. To date, although various therapeutic methods, including radiotherapy (RT), chemotherapy, chemodynamic therapy (CDT), phototherapy, starvation therapy, and immunotherapy, have entered a new stage of rapid progress in cancer theranostics, their limited therapeutic effect and significant side effects need to be considered carefully. With the rapid development of nanotechnology, the marriage of nanomaterials and therapeutic methods provides the practical possibility to improve the deficiencies in cancer therapy. Notably, metal-organic frameworks (MOFs) composed of ions/clusters and bridging ligands through coordination bonds have been widely applied in cancer therapy to deal with the drawbacks of different therapeutic methods, such as severe side effects, low stability, and poor efficacy, owing to their controllable morphologies, tailorable diameters, diverse compositions, tunable porosities, high specific surface areas, facile functionalization, and good biocompatibility. This review summarizes the recent advanced developments and achievements of multifunctional MOF-based nanoplatforms for cancer therapy through single therapy methods, including RT, chemotherapy, CDT, phototherapy (photodynamic and photothermal therapy), starvation therapy and immunotherapy, and combination therapy methods. Moreover, the prospects and challenges of MOF-based nanoplatforms used in tumor therapy are also discussed.
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Estructuras Metalorgánicas , Nanoestructuras , Neoplasias , Humanos , Estructuras Metalorgánicas/uso terapéutico , Estructuras Metalorgánicas/química , Fototerapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Nanoestructuras/química , Portadores de Fármacos/químicaRESUMEN
The success of messenger RNA therapeutics largely depends on the availability of delivery systems that enable the safe, effective and stable translation of genetic material into functional proteins. Here we show that extracellular vesicles (EVs) produced via cellular nanoporation from human dermal fibroblasts, and encapsulating mRNA encoding for extracellular-matrix α1 type-I collagen (COL1A1) induced the formation of collagen-protein grafts and reduced wrinkle formation in the collagen-depleted dermal tissue of mice with photoaged skin. We also show that the intradermal delivery of the mRNA-loaded EVs via a microneedle array led to the prolonged and more uniform synthesis and replacement of collagen in the dermis of the animals. The intradermal delivery of EV-based COL1A1 mRNA may make for an effective protein-replacement therapy for the treatment of photoaged skin.
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Dermis , Vesículas Extracelulares , Humanos , Ratones , Animales , Dermis/metabolismo , ARN Mensajero/metabolismo , Colágeno/metabolismo , Piel/metabolismo , Vesículas Extracelulares/metabolismoRESUMEN
Purpose: Effective therapy for rheumatoid arthritis (RA) keeps a challenge due to the complex pathogenesis of RA. It is not enough to completely inhibit the process of RA with any single therapy method. The purpose of the research is to compensate for the insufficiency of monotherapy using multiple treatment regimens with different mechanisms. Material and Methods: In this study, we developed a new method to synthesize mesoporous silica nanoparticles hybridized with photosensitizer PCPDTBT (HNs). Branched polyethyleneimine-folic acid (PEI-FA) could be coated on the surface of HNs through electrostatic interactions. It simultaneously blocked the hypoxia-activated prodrug tirapazamine loaded into the mesopores and binded with Mcl-1 siRNA (siMcl-1) that interfered with the expression of the anti-apoptotic protein Mcl-1. Released from the co-delivery nanoparticles (PFHNs/TM) Tirapazamine and siMcl-1 upon exposure to acidic conditions of endosomes/lysosomes in activated macrophages. Under NIR irradiation, photothermal therapy and photodynamic therapy derived from PCPDTBT, hypoxia-activated chemotherapy derived from tirapazamine, and RNAi derived from siMcl-1 were used for the combined treatment for RA by killing activated macrophages. PEI-FA-coated PFHNs/TM exhibited activated macrophage-targeting characteristics, thereby enhancing the in vitro and in vivo NIR-induced combined treatment of RA. Results: The prepared PFHNs/TM have high blood compatibility (far below 5% of hemolysis) and ideal in vitro phototherapy effect while controlling the TPZ release and binding siMcl-1. We prove that PEI-FA-coated PFHNs/TM not only protect the bound siRNA but also are selectively uptaked by activated macrophages through FA receptor-ligand-mediated endocytosis, and effectively silence the target anti-apoptotic protein by siMcl-1 transfection. In vivo, PFHNs/TM have also been revealed to be selectively enriched at the inflammatory site of RA, exhibiting NIR-induced anti-RA efficacy. Conclusion: Overall, these FA-functionalized, pH-responsive PFHNs/TM represent a promising platform for the co-delivery of chemical drugs and nucleic acids for the treatment of RA cooperating with NIR-induced phototherapy.
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Artritis Reumatoide , Nanopartículas , Humanos , Tirapazamina/farmacología , Interferencia de ARN , Sistema de Administración de Fármacos con Nanopartículas , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Fototerapia/métodos , Artritis Reumatoide/tratamiento farmacológico , ARN Interferente Pequeño , Ácido Fólico , HipoxiaRESUMEN
Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of anticancer nano-drug delivery systems. However, problems still exist in the delicate balance between improved anticancer efficacy and reduced toxicity to normal tissues, and opportunities arise along with the development of smart stimuli-responsive delivery strategies. By on-demand responsiveness towards exogenous or endogenous stimulus, these smart delivery systems hold promise for advanced tumor-specificity as well as controllable release behavior in a spatial-temporal manner. Meanwhile, the blossom of nanotechnology, material sciences, and biomedical sciences has shed light on the diverse modern drug delivery systems with smart characteristics, versatile functions, and modification possibilities. This review summarizes the current progress in various strategies for smart drug delivery systems against malignancies and introduces the representative endogenous and exogenous stimuli-responsive smart delivery systems. It may provide references for researchers in the fields of drug delivery, biomaterials, and nanotechnology.
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Liver fibrosis is the deposition of extracellular matrix (ECM) in the liver caused by persistent chronic injury, which can lead to more serious diseases such as cirrhosis or cancer. Blocking the effect of transforming growth factor ß1 (TGF-ß1), one of the most important cytokines in liver fibrosis, may be one of the effective ways to inhibit liver fibrosis. As a kind of natural nano-scale vesicles, small extracellular vesicles (sEvs) have displayed excellent delivery vehicle properties. Herein, we prepared hepatic stellate cell (HSC)-derived sEvs loading left-right determination factor 1 (lefty1) mRNA (sEvLs) and we wanted to verify whether they can inhibit fibrosis by blocking the TGF-ß1 signaling pathway. The results showed that sEvLs had effective cell uptake and reduced activation of HSCs. Rats that were injected with CCl4 by intraperitoneal injection for 6 weeks exhibited obvious symptoms of liver fibrosis and were treated with systemically administered sEvLs and free sEvs for 4 weeks. Rats injected with olive oil alone served as sham controls. Administration of sEvLs significantly reduced the area of fibrosis compared with free sEvs. We demonstrated that sEvLs inhibited HSCs activation and ECM production, and promote ECM degradation by downregulating α-smooth muscle actin (α-SMA), collagen I, tissue inhibitor of metalloproteinase (TIMP) -1 and upregulating matrix metalloprotease (MMP) -1. In summary, as an endogenous delivery vehicle, sEvs could deliver mRNA to attenuate hepatic fibrosis by blocking the TGF-ß/Smad signaling pathway.
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A co-delivery system of SN38 (7-ethyl-10-hydroxyl camptothecin) prodrug and CUR (curcumin) was designed for the treatment of lung cancer by pulmonary delivery. SN38 was linked to cell-penetrating peptide (CPP) TAT via a polyethylene glycol (PEG) linker to form the SN38 prodrug (TAT-PEG-SN38). Liposomes co-loaded with amphiphilic TAT-PEG-SN38 and curcumin (Lip-TAT-PEG-SN38/CUR) were successfully prepared by a microfluidic method for the treatment of lung cancer via pulmonary delivery. Lip-TAT-PEG-SN38/CUR showed nanometer-sized sphericity and a particle size of 171.21 nm. Besides, Lip-TAT-PEG-SN38/CUR exhibited enhanced antiproliferative effect, increased cell apoptosis induction and improved cell cycle arrest compared to the single agents in vitro. The combination induced significant tumor inhibition in a BALB/c mouse lung cancer model. These results indicated that our SN38 prodrug and curcumin co-delivery system was a promising candidate for lung cancer treatment.
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Péptidos de Penetración Celular , Curcumina , Neoplasias Pulmonares , Nanopartículas , Profármacos , Animales , Camptotecina , Línea Celular Tumoral , Curcumina/farmacología , Sistemas de Liberación de Medicamentos/métodos , Liposomas , Neoplasias Pulmonares/tratamiento farmacológico , Ratones , Polietilenglicoles , Profármacos/farmacologíaRESUMEN
As an important means of communication among cells, exosomes are being studied more and more widely, especially in the context of cancer immunotherapy. In the phase of tumor immunoediting, exosomes derived from tumor cells and different immune cells have complex and changeable physiological functions, because they carry different proteins and nucleic acid from the source cells. Based on the role of exosomes in the communication between different cells, cancer treatment methods are also under continuous research. This review briefly introduces the molecular composition of exosomes, which is closely related to their secretion mechanism. Subsequently, the role of exosomes encapsulating different information molecules is summarized. The role of exosomes in the three phases of tumor immunoediting is introduced in detail, and the relevant literature of exosomes in the tumor immune microenvironment is summarized by using a novel framework for extracting relevant documents. Finally, it summarizes the various exosome-based immunotherapies currently proposed, as well as the challenges and future prospects of exosomes in tumor immunotherapy.
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Verbascoside (VB) is a phenylethanoid glycoside extracted from the herbaceous plant Verbascum sinuatum and plays a neuroprotective role in Alzheimer's disease (AD). The goal of this study was to explore the neuroprotective mechanism of VB. Based on the proteomics analysis, immunohistochemistry, immunofluorescence, Western blot, and ELISA were utilized to explore the neuroprotective mechanism of VB in context of neuroinflammation in APP/PS1 mice, LPS-induced BV2 cells, and/or Aß1-42-stimulated N2a cells. Proteomic analysis demonstrated that the neuroprotection of VB correlated closely to its anti-inflammatory effect. VB significantly blocked microglia and astrocyte against activation in brains of APP/PS1 mice, suppressed the generation of IL-1ß as well as IL-6, and boosted that of IL-4, IL-10 and TGF-ß in vivo, which were analogous to results acquired in vitro. Furthermore, VB effectively restrained the phosphorylation of IKKα+ß, IκBα, and NF-κB-p65 in APP/PS1 mice; LPS-induced BV2 cells, and Aß1-42-stimulated N2a cells and lowered the tendency of NF-κB-p65 translocation towards nucleus in vitro. These results demonstrate that the neuroprotective effect of VB correlates to the modulation of neuroinflammation via NF-κB-p65 pathway, making VB as a hopeful candidate drug for the prevention and treatment of AD.