RESUMEN
Cerasomes are a promising modification of liposomes with covalent siloxane networks on the surface that provide outstanding morphological stability while maintaining all the useful traits of liposomes. Herein, thin film hydration and ethanol sol injection methods were utilized to produce cerasomes of various composition, which were then evaluated for the purpose of drug delivery. The most promising nanoparticles obtained by the thin film method were studied closely using MTT assay, flow cytometry and fluorescence microscopy on T98G glioblastoma cell line and modified with surfactants to achieve stability and the ability to bypass the blood-brain barrier. An antitumor agent, paclitaxel, was loaded into cerasomes, which increased its potency and demonstrated increased ability to induce apoptosis in T98G glioblastoma cell culture. Cerasomes loaded with fluorescent dye rhodamine B demonstrated significantly increased fluorescence in brain slices of Wistar rats compared to free rhodamine B. Thin film hydration with Tween 80 addition was established as a more reliable and versatile method for cerasome preparation. Cerasomes increased the antitumor action of paclitaxel toward T98G cancer cells by a factor of 36 and were able to deliver rhodamine B over the blood-brain barrier in rats.
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Glioblastoma , Liposomas , Ratas , Animales , Ratas Wistar , Sistemas de Liberación de Medicamentos/métodos , Paclitaxel , Lípidos , Línea Celular TumoralRESUMEN
A simple and sensitive electrochemical cholesterol biosensor was fabricated based on ceramic-coated liposome (cerasome) and graphene quantum dots (GQDs) with good conductivity. The cerasome consists of a lipid-bilayer membrane and a ceramic surface as a soft biomimetic interface, and the mild layer-by-layer self-assembled method as the immobilization strategy on the surface of the modified electrode was used, which can provide good biocompatibility to maintain the biological activity of cholesterol oxidase (ChOx). The GQDs promoted electron transport between the enzyme and the electrode more effectively. The structure of the cerasome-forming lipid was characterized by Fourier transform infrared (FT-IR). The morphology and characteristics of the cerasome and GQDs were characterized by transmission electron microscopy (TEM), zeta potential, photoluminescence spectra (PL), etc. The proposed biosensors revealed excellent catalytic performance to cholesterol with a linear concentration range of 16.0 × 10-6-6.186 × 10-3 mol/L, with a low detection limit (LOD) of 5.0 × 10-6 mol/L. The Michaelis-Menten constant (Km) of ChOx was 5.46 mmol/L, indicating that the immobilized ChOx on the PEI/GQDs/PEI/cerasome-modified electrode has a good affinity to cholesterol. Moreover, the as-fabricated electrochemical biosensor exhibited good stability, anti-interference ability, and practical application for cholesterol detection.
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Técnicas Biosensibles , Grafito , Puntos Cuánticos , Biomimética , Técnicas Biosensibles/métodos , Colesterol , Colesterol Oxidasa/química , Técnicas Electroquímicas , Grafito/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Encapsulation of cargoes in nanocontainers is widely used in different fields to solve the problems of their solubility, homogeneity, stability, protection from unwanted chemical and biological destructive effects, and functional activity improvement. This approach is of special importance in biomedicine, since this makes it possible to reduce the limitations of drug delivery related to the toxicity and side effects of therapeutics, their low bioavailability and biocompatibility. This review highlights current progress in the use of lipid systems to deliver active substances to the human body. Various lipid compositions modified with amphiphilic open-chain and macrocyclic compounds, peptide molecules and alternative target ligands are discussed. Liposome modification also evolves by creating new hybrid structures consisting of organic and inorganic parts. Such nanohybrid platforms include cerasomes, which are considered as alternative nanocarriers allowing to reduce inherent limitations of lipid nanoparticles. Compositions based on mesoporous silica are beginning to acquire no less relevance due to their unique features, such as advanced porous properties, well-proven drug delivery efficiency and their versatility for creating highly efficient nanomaterials. The types of silica nanoparticles, their efficacy in biomedical applications and hybrid inorganic-polymer platforms are the subject of discussion in this review, with current challenges emphasized.
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Lípidos/química , Nanopartículas/química , Disponibilidad Biológica , Portadores de Fármacos , Composición de Medicamentos , Ligandos , Porosidad , Dióxido de SilicioRESUMEN
Rotator cuff tear (RCT) is a prevalent shoulder injury that poses challenges for achieving continuous and functional regeneration of the tendon-to-bone interface (TBI). In this study, we controlled the delivery of growth factors (GFs) from liposomal nanohybrid cerasomes by ultrasound and implanted three-dimensional printed polycaprolactone (PCL) scaffolds modified with polydopamine loaded with bone marrow mesenchymal stem cells (BMSCs) to repair tears of the infraspinatus tendon in a lapine model. Direct suturing (control, CTL) was used as a control. The PCL/BMSC/cerasome (PBC) devices are sutured with the enthesis of the infraspinatus tendon. The cerasomes and PCL scaffolds are highly stable with excellent biocompatibility. The roles of GFs BMP2, TGFß1, and FGF2 in tissue-specific differentiation are validated. Compared with the CTL group, the PBC group had significantly greater proteoglycan deposition (P = 0.0218), collagen volume fraction (P = 0.0078), and proportions of collagen I (P = 0.0085) and collagen III (P = 0.0048). Biotin-labeled in situ hybridization revealed a high rate of survival for transplanted BMSCs. Collagen type co-staining at the TBI is consistent with multiple collagen regeneration. Our studies demonstrate the validity of biomimetic scaffolds of TBI with BMSC-seeded PCL scaffolds and GF-loaded cerasomes to enhance the treatment outcomes for RCTs.
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Células Madre Mesenquimatosas , Poliésteres , Andamios del Tejido , Biomimética , Tendones , Colágeno/metabolismo , Péptidos y Proteínas de Señalización Intercelular/farmacología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Células de la Médula ÓseaRESUMEN
Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration, resulting in dopamine depletion and motor behavior deficits. Since the discovery of L-DOPA, it has been the most prescribed drug for symptomatic relief in PD, whose prolonged use, however, causes undesirable motor fluctuations like dyskinesia and dystonia. Further, therapeutics targeting the pathological hallmarks of PD including α-synuclein aggregation, oxidative stress, neuroinflammation, and autophagy impairment have also been developed, yet PD treatment is a largely unmet success. The inception of the nanovesicle-based drug delivery approach over the past few decades brings add-on advantages to the therapeutic strategies for PD treatment in which nanovesicles (basically phospholipid-containing artificial structures) are used to load and deliver drugs to the target site of the body. The present review narrates the characteristic features of nanovesicles including their blood-brain barrier permeability and ability to reach dopaminergic neurons of the brain and finally discusses the current status of this technology in the treatment of PD. From the review, it becomes evident that with the assistance of nanovesicle technology, the therapeutic efficacy of anti-PD pharmaceuticals, phyto-compounds, as well as that of nucleic acids targeting α-synuclein aggregation gained a significant increment. Furthermore, owing to the multiple drug-carrying abilities of nanovesicles, combination therapy targeting multiple pathogenic events of PD has also found success in preclinical studies and will plausibly lead to effective treatment strategies in the near future.
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Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patología , alfa-Sinucleína/metabolismo , Dopamina/farmacología , Levodopa/farmacología , Levodopa/uso terapéutico , Encéfalo/metabolismo , Neuronas Dopaminérgicas/metabolismoRESUMEN
A novel liposomal nanocomposite, Au@PIL-cerasome, with biocompatibility and conductivity was fabricated via the self-assembly of cerasomes and gold nanoparticles (AuNPs) stabilized by poly(ionic liquid)s (PILs). The surface charge, morphology and chemical composition of the nanocomposites were characterized by the zeta potential, UV-vis, TEM, SEM and EDS. The nanocomposites exhibited structural stability directly on the surface of solid electrodes, without fusion. Electrochemical impedance experiments demonstrated that the nanocomposites had an enhanced conductivity compared with unmodified cerasomes. Horseradish peroxidase (HRP), as a reporter, was immobilized on the nanocomposites without denaturation or inactivation. The direct electron transfer of HRP was achieved, and the HRP/Au@PIL-cerasome/GCE exhibited an amplified current and improved electrocatalytic activity. Activity towards H2O2 displayed a linear range over 10-70 µM and a detection limit of 3.3 µM. Activity towards NO2- displayed linear ranges over 1-5 mM and 5-1280 mM, and the limit of detection was 0.11 mM. In addition, the electrode was stable and reproducible, with 6% RSD. Such multi-component liposomal nanocomposites with an enhanced electrical performance pave a better way for building novel and straightforward 3D stereo biomimetic electrochemical platforms and even molecular communication systems to investigate information transduction between cells.
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Biomimética , Técnicas Electroquímicas/métodos , Oro/química , Líquidos Iónicos/química , Nanopartículas del Metal/química , Propiedades de SuperficieRESUMEN
Thermosensitive liposomes have demonstrated great potential for tumor-specific chemotherapy. Near infrared (NIR) dyes loaded liposomes have also shown improved photothermal effect in cancer theranostics. However, the instability of liposomes often causes premature release of drugs or dyes, impeding their antitumor efficacy. Herein, we fabricated a highly stable thermo-responsive bubble-generating liposomal nanohybrid cerasome with a silicate framework, combined with a NIR dye to achieve NIR light stimulated, tumor-specific, chemo-photothermal synergistic therapy. Methods: In this system, NIR dye of 1,1'-Dioctadecyl-3,3,3',3'- Tetramethylindotricarbocyanine iodide (DiR) with long carbon chains was self-assembled with a cerasome-forming lipid (CFL) to encapsulate ammonium bicarbonate (ABC), which was further used for actively loading doxorubicin (DOX), affording a thermosensitive and photosensitive DOX-DiR@cerasome (ABC). Results: The resulting cerasome could disperse well in different media. Upon NIR light mediated thermal effect, ABC was decomposed to generate CO2 bubbles, resulting in a permeable channel in the cerasome bilayer that significantly enhanced DOX release. After intravenous injection into tumor-bearing mice, DOX-DiR@cerasome (ABC) could be efficiently accumulated at the tumor tissue, as monitored by DiR fluorescence, lasting for more than 5 days. NIR light irradiation was then performed at 36h to locally heat the tumors, resulting in immediate CO2 bubble generation, which could be clearly detected by ultrasound imaging, facilitating the monitoring process of controlled release of the drug. Significant antitumor efficacy could be obtained for the DOX-DiR@cerasome (ABC) + laser group, which was further confirmed by tumor tissue histological analysis.
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Terapia Combinada/métodos , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas , Neoplasias/tratamiento farmacológico , Animales , Línea Celular Tumoral , Portadores de Fármacos , Liberación de Fármacos , Quimioterapia/métodos , Colorantes Fluorescentes , Liposomas/química , Liposomas/uso terapéutico , Ratones , Nanopartículas/química , Nanopartículas/uso terapéutico , Neoplasias/diagnóstico por imagen , Fototerapia/métodos , UltrasonografíaRESUMEN
Drug carriers with tumor targeting and controlled release have strong prospects for application in safe and efficient chemotherapy. Among various carriers, liposomes have good biocompatibility and can enhance the uptake of drugs by cancer cells. However, traditional liposomes have no specific targeting to cancer cells and are prone to insufficient stability, causing early leakage of the drug. Accordingly, organic-inorganic hybrid phospholipid and thermosensitive phospholipid are deliberately introduced into a liposome system to enhance the morphological and structural stability of the liposomes while realizing thermally controlled drug release. Furthermore, modification with a targeting ligand (WSG-peptide) can endow liposomes with active targeting to ovarian carcinoma cells. First, WSG-peptide was grafted onto the hydrophilic terminal of phospholipid molecules, and the organic-inorganic hybrid cerasome-forming lipid (CFL) was synthesized via a two-step chemical reaction. Then, the WSG-grafted thermosensitive liposomal cerasome (c-LIP-WSG) was prepared by thin-film hydration method. The results showed that the c-LIP-WSG had excellent structural stability both in storage and in a simulated circulation environment. In vitro drug release confirmed that the liposomes exhibited thermally controlled release. Cell uptake experiments and living fluorescence imaging of SKOV-3 tumor-bearing nude mice confirmed that the WSG-peptide modified liposomes were provided with specific targeting properties for ovarian carcinoma.
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Antineoplásicos/química , Antineoplásicos/farmacología , Alcaloides de Berberina/química , Alcaloides de Berberina/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacología , Liposomas/química , Animales , Línea Celular , Línea Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacología , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Femenino , Calor , Células Endoteliales de la Vena Umbilical Humana , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Ligandos , Ratones , Ratones Desnudos , Neoplasias Ováricas/tratamiento farmacológico , Péptidos/química , TemperaturaRESUMEN
Rationale: Treatment for Parkinson's disease (PD) is challenged by the presence of the blood-brain barrier (BBB) that significantly limits the effective drug concentration in a patient's brain for therapeutic response throughout various stages of PD. Curcumin holds the potential for α-synuclein clearance to treat PD; however, its applications are still limited due to its low bioavailability and poor permeability through the BBB in a free form. Methods: Herein, this paper fabricated curcumin-loaded polysorbate 80-modified cerasome (CPC) nanoparticles (NPs) with a mean diameter of ~110 nm for enhancing the localized curcumin delivery into the targeted brain nuclei via effective BBB opening in combination with ultrasound-targeted microbubble destruction (UTMD). Results: The liposomal nanohybrid cerasome exhibited superior stability towards PS 80 surfactant solubilization and longer circulation lifetime (t1/2 = 6.22 h), much longer than free curcumin (t1/2 = 0.76 h). The permeation was found to be 1.7-fold higher than that of CPC treatment only at 6 h after the systemic administration of CPC NPs. Notably, motor behaviors, dopamine (DA) level and tyrosine hydroxylase (TH) expression all returned to normal, thanks to α-synuclein (AS) removal mediated by efficient curcumin delivery to the striatum. Most importantly, the animal experiment demonstrated that the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice had notably improved behavior disorder and dopamine depletion during two-week post-observation after treatment with CPC NPs (15 mg curcumin/kg) coupled with UTMD. Conclusion: This novel CPC-UTMD formulation approach could be an effective, safe and amenable choice with higher therapeutic relevance and fewer unwanted complications than conventional chemotherapeutics delivery systems for PD treatment in the near future.
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Encéfalo/metabolismo , Curcumina/administración & dosificación , Curcumina/farmacología , Sistemas de Liberación de Medicamentos , Microburbujas , Enfermedad de Parkinson/diagnóstico por imagen , Polisorbatos/química , Animales , Encéfalo/efectos de los fármacos , Curcumina/química , Curcumina/farmacocinética , Dopamina/metabolismo , Hidrodinámica , Liposomas , Ratones Endogámicos C57BL , Modelos Biológicos , Actividad Motora , Neostriado/metabolismo , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Tamaño de la Partícula , Permeabilidad , Electricidad Estática , Distribución Tisular , UltrasonografíaRESUMEN
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a higher risk in younger women and a poorer prognosis and without targeted therapies available currently. Cancer stem cells (CSCs) are increasingly recognized as the main cause of treatment failure and tumor recurrence. The present paper reports the encapsulation of lovastatin (LV) into cerasomes. Compared with free LV, cerasome-encapsulated LV (C-LV) nanohybrids showed cytotoxicity to MDA-MB-231 CSCs in a dose- and time-dependent manner. Furthermore, intravenous injection of C-LV nanohybrids resulted in a significant tumor size reduction in a dose-dependent manner in xenograft tumors derived from subcutaneous inoculation of MDA-MB-231 cells. Furthermore, histopathological and/or immunohistochemical analysis revealed that C-LV nanohybrids significantly induced mammary gland formation and apoptosis and inhibited angiogenesis, the CSC phenotype, and the epithelial-to-mesenchymal transition in xenograft tumors. Most importantly, C-LV nanohybrids were found to be more effective than free LV in inhibiting the growth of breast cancer xenografts and the stemness properties in vivo. To the best of our knowledge, ours is the first demonstration of nanohybrids for efficient inhibition of CSCs derived from TNBC, offering a new option for the TNBC treatment.
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Neoplasias de la Mama Triple Negativas , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Transición Epitelial-Mesenquimal , Femenino , Humanos , Lovastatina , Células Madre NeoplásicasRESUMEN
BACKGROUND: Liposomes have been widely used in gene transfection and drug delivery systems due to their excellent biocompatibility and encapsulation ability, especially, the ability to deliver the gene/drug into the cells via the membrane fusion. Thermosensitive liposomes have been proven to be a precise and effective method for cancer treatment in many preclinical studies. But the imperfect crystalline arrangement between grains occurred, resulting in planar defects at the boundaries of membranes, compromising the stability of thermosensitive liposomes. OBJECTIVE: In the present study, we developed a facile method to improve the stability of ordinary thermosensitive liposomes by introducing organic-inorganic hybrid materials with local Si-O-Si net. METHOD: A cerasome forming lipid, N, N-Dihxadecyl-N'- [(3-triethoxysilyl) propyl] urea, was synthesized and then introduced into the thermosensitive lipids to form the composite liposomes (named as cera-liposomes). The effects of the cerasome forming lipid on the cera-liposomes characteristics, including the morphology, drug loading, Zeta potential and stability of vesicles, were investigated. RESULTS: Cera-liposomes were thermosensitive, and they had a loading efficiency over 2 folds more than conventional thermosensitive liposomes. With the enhanced sustain of Si-O-Si, cera-liposomes were able to avoid collapsing and fusing during storage, and had a good resistance to nonionic surfactant. More than 80% drug was still retained after storage of 15 days at room temperature. CONCLUSION: The cerasome forming lipid showed potential in improving the stability of thermosensitive liposomes. This novel kind of cera-liposomes could be a stable and effective drug carrier for anticancer applications.
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Sistemas de Liberación de Medicamentos/métodos , Liposomas/química , Oxígeno/química , Silicio/química , Urea/química , Doxorrubicina/química , Estabilidad de Medicamentos , Liposomas/ultraestructura , Transición de Fase , Propiedades de SuperficieRESUMEN
Cerasome is a freshly developped bilayer vehicle that resemble traditional liposome but has higher mophorlogical stability. In this study, a novel redox-responsive cerasome (RRC) was developed for tumor-targeting drug delivery. The cerasome-forming lipid (CFL) that comprise a cleavable disulfide bond as connector unit of the triethoxysilyl head and the hydrophobic alkyl double chain was synthesized and subsequently used to prepare cerasome through ethanol injection method. RRC that has liposome-resembling lipid bilayer structure was proved being outstanding at drug loading capacity as well as morphological stability as compared to conventional liposomes. In addition, in vitro drug release tests of DOX/RRCs showed a redox-responsive drug release profile: accelerated DOX releasing compared to reduction-insensitive cerasomes (RICs) in the presence of 10mM of GSH. Under the same condition, the reduction sensibility of RRC was further proved by increased hydrodynamic diameter and destroying of integrity from DLS and SEM results. RRC showed non-toxic to human embryonic kidney 293 cells, indicating that this material has good biocompatibility. On the other hand, DOX/RRCs showed a resemble IC50 (half inhibitory concentration) value to that of free DOX to human hepatoma SMMC-7721 cells and breast cancer MCF-7 cells. IC50 values at 48h were found to decrease in the following order: DOX/RIC>DOX/RRC>DOX. Taken together, the RRC developped in this study is of great potential to be utilized as a promising platform for intracellular anticancer drug delivery.
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Portadores de Fármacos/química , Membrana Dobles de Lípidos/química , Liposomas/química , Nanoestructuras/química , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Estabilidad de Medicamentos , Células HEK293 , Humanos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Espacio Intracelular/metabolismo , Células MCF-7 , Microscopía Electrónica de Rastreo , Nanoestructuras/ultraestructura , Oxidación-ReducciónRESUMEN
A novel fluorescent nanohybrid was fabricated via the self-assembly of semiconductive quantum dots (QDs) on biocompatible cerasomes. The nanohybrid (denoted as QDs-cerasome) was used as an electrode material for visible protein immobilization and bioelectrochemistry. The morphology and surface properties of the QDs-cerasome hybrid were characterized by transmission electron microscopies, atomic force microscopies and zeta potential measurements. Because the QDs-cerasome hybrid possessed a positive charge in aqueous solution, it could be used as a matrix to immobilize negatively charged hemoglobin (Hb) via electrostatic interaction. Ultraviolet-visible spectroscopy demonstrated that Hb was immobilized on the hybrid matrix without denaturation. The fluorescence of the QDs-cerasome was quenched as Hb was immobilized, indicating that the protein immobilization process could be visibly detected. Compared with protein electrodes constructed using a single-component material, including Hb-QDs/GC and Hb-cerasome/GC electrodes, the Hb-QDs-cerasome/GC electrode not only realized enhanced direct electrochemistry, but also displayed higher sensitivity and a wider linear range toward the detection of hydrogen peroxide because of the synergistic effect of the QDs and cerasomes. The experimental results demonstrate that this fluorescent multicomponent hybrid material provides a novel and effective platform to immobilize a redox protein to realize direct electrochemistry. As such, this hybrid shows promise for application in third-generation electrochemical biosensors.
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Puntos Cuánticos , Técnicas Biosensibles , Catálisis , Técnicas Electroquímicas , Electrodos , Hemoglobinas , Peróxido de HidrógenoRESUMEN
This Article reported the fabrication of a robust theranostic cerasome encapsulating indocyanine green (ICG) by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)2000]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DSPE-PEG2000-DOTA), followed by chelating radioisotope of (177)Lu. Its applications in optical and nuclear imaging of tumor uptake and biodistribution, as well as photothermal killing of cancer cells, were investigated. It was found that the obtained cerasome could act efficiently as fluorescence contrast agent as well as nuclear imaging tracer. Encapsulating ICG into cerasome could protect ICG from degradation, aggregation, and fast elimination from body, resulting in remarkable improvement in near-infrared fluorescence imaging, photothermal stability, and in vivo pharmacokinetic profile. Both fluorescence and nuclear imaging showed that such agent could selectively accumulate in tumor site after intravenous injection of the cerasome agent into Lewis lung carcinoma tumor bearing mice, resulting in efficient photothermal ablation of tumor through a one-time NIR laser irradiation at the best time window. The ability to track the uptake of cerasomes on a whole body basis could provide researchers with an excellent tool for developing cerasome-based drug delivery agents, especially the strategy of labeling cerasomes with theranostic radionuclide (177)Lu, enabling the ability of the (177)Lu-labeled cerasomes for radionuclide cancer therapy and even the combined therapy.