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1.
Nat Commun ; 12(1): 1999, 2021 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-33790276

RESUMEN

Intratumoral immunotherapy is an emerging modality for the treatment of solid tumors. Toll-like receptor (TLR) agonists have shown promise for eliciting immune responses, but systemic administration often results in the development of adverse side effects. Herein, we investigate whether localized delivery of the TLR agonist, resiquimod (R848), via platelet membrane-coated nanoparticles (PNP-R848) elicits antitumor responses. The membrane coating provides a means of enhancing interactions with the tumor microenvironment, thereby maximizing the activity of R848. Intratumoral administration of PNP-R848 strongly enhances local immune activation and leads to complete tumor regression in a colorectal tumor model, while providing protection against repeated tumor re-challenges. Moreover, treatment of an aggressive breast cancer model with intratumoral PNP-R848 delays tumor growth and inhibits lung metastasis. Our findings highlight the promise of locally delivering immunostimulatory payloads using biomimetic nanocarriers, which possess advantages such as enhanced biocompatibility and natural targeting affinities.


Asunto(s)
Imidazoles/uso terapéutico , Inmunoterapia/métodos , Nanopartículas/uso terapéutico , Neoplasias/terapia , Microambiente Tumoral/efectos de los fármacos , Animales , Plaquetas/química , Plaquetas/metabolismo , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Línea Celular Tumoral , Membrana Celular/química , Membrana Celular/metabolismo , Células Cultivadas , Femenino , Células HT29 , Humanos , Imidazoles/química , Imidazoles/inmunología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Ratones Endogámicos C57BL , Nanopartículas/química , Neoplasias/inmunología , Neoplasias/patología , Resultado del Tratamiento , Microambiente Tumoral/inmunología
2.
Int J Nanomedicine ; 16: 2585-2595, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33833513

RESUMEN

Background: In cancer nanomedicine, drugs are transported by nanocarriers through a biological system to produce a therapeutic effect. The efficacy of the treatment is affected by the ability of the nanocarriers to overcome biological transport barriers to reach their target. In this work, we focus on the process of nanocarrier penetration through tumour tissue after extravasation. Visualising the dynamics of nanocarriers in tissue is difficult in vivo, and in vitro assays often do not capture the spatial and physical constraints relevant to model tissue penetration. Methods: We propose a new simple, low-cost method to observe the transport dynamics of nanoparticles through a tissue-mimetic microfluidic chip. After loading a chip with triplicate conditions of gel type and loading with microparticles, microscopic analysis allows for tracking of fluorescent nanoparticles as they move through hydrogels (Matrigel and Collagen I) with and without cell-sized microparticles. A bespoke image-processing codebase written in MATLAB allows for statistical analysis of this tracking, and time-dependent dynamics can be determined. Results: To demonstrate the method, we show size-dependence of transport mechanics can be observed, with diffusion of fluorescein dye throughout the channel in 8 h, while 20 nm carboxylate FluoSphere diffusion was hindered through both Collagen I and Matrigel™. Statistical measurements of the results are generated through the software package and show the significance of both size and presence of microparticles on penetration depth. Conclusion: This provides an easy-to-understand output for the end user to measure nanoparticle tissue penetration, enabling the first steps towards future automated experimentation of transport dynamics for rational nanocarrier design.


Asunto(s)
Geles/química , Microfluídica/métodos , Nanopartículas/administración & dosificación , Nanopartículas/metabolismo , Andamios del Tejido/química , Colágeno/química , Colágeno/metabolismo , Difusión , Humanos , Nanomedicina/métodos , Nanopartículas/química
3.
Int J Nanomedicine ; 16: 2597-2613, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33833514

RESUMEN

Introduction: Limited by tumor vascular barriers, restricted intratumoural T cell infiltration and nanoparticles accumulation remain major bottlenecks for anticancer therapy. Platelets are now known to maintain tumor vascular integrity. Therefore, inhibition of tumor-associated platelets may be an effective method to increase T cell infiltration and drug accumulation at tumor sites. Herein, we designed an ultrasound-responsive nitric oxide (NO) release nanosystem, SNO-HSA-PTX, which can release NO in response to ultrasound (US) irradiation, thereby inhibiting platelet function and opening the tumor vascular barrier, promoting drug accumulation and T cell infiltration. Methods: We evaluated the ability of SNO-HSA-PTX to release NO in response to US irradiation. We also tested the effect of SNO-HSA-PTX on platelet function. Plenty of studies including cytotoxicity, pharmacokinetics study, biodistribution, blood perfusion, T cell infiltration, in vivo antitumor efficacy and safety assessment were conducted to investigate the antitumor effect of SNO-HSA-PTX. Results: SNO-HSA-PTX with US irradiation inhibited tumor-associated platelets activation and induced openings in the tumor vascular barriers, which promoted the accumulation of SNO-HSA-PTX nanoparticles to the tumor sites. Meanwhile, the damaged vascular barriers allowed oxygen-carrying hemoglobin to infiltrate tumor regions, alleviating hypoxia of the tumor microenvironment. In addition, the intratumoral T cell infiltration was augmented, together with chemotherapy and NO therapy, which greatly inhibited tumor growth. Discussion: Our research designed a simple strategy to open the vascular barrier by inhibiting the tumor-associated platelets, which provide new ideas for anti-tumor treatment.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Linfocitos Infiltrantes de Tumor/inmunología , Nanopartículas/administración & dosificación , Óxido Nítrico/metabolismo , Compuestos Nitrosos/química , Paclitaxel/farmacología , Albúmina Sérica Humana/química , Ondas Ultrasónicas , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/farmacología , Apoptosis , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/química , Paclitaxel/administración & dosificación , Paclitaxel/farmacocinética , Distribución Tisular , Células Tumorales Cultivadas , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Georgian Med News ; (311): 173-177, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33814414

RESUMEN

The purpose of this study was to evaluate effect of process and formulation variables on the preparation of Erysimum extract loaded PLGA nanoparticles. The influence of the various biopharmaceutical factors such as type of organic solvent, type and concentration of surfactant, polymer concentration in the organic phase, ratio of organic phase and water phase were studied. Modified emulsification solvent evaporation method was used for preparation of nanoparticles. Based on the performed experiments optimal formulation of nanocomposite is suggested. Nanoparticle size, size distribution and entrapment efficiency were determined. Among five non-ionic surfactants polyvinyl alcohol provided more stable nanocomposite. Influence mechanisms of different surfactants on nanoparticle formation are provided. Water miscible organic solvent, acetone obtained 232 nm nanoparticles with improved size distribution. Entrapment efficiency was increased to 73% by reducing ratio of organic and water phases. Based on experiments nanoparticles with stable, reproducible properties are fabricated.


Asunto(s)
Productos Biológicos , Erysimum , Nanopartículas , Portadores de Fármacos , Ácido Láctico , Tamaño de la Partícula , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico
5.
Int J Nanomedicine ; 16: 2357-2372, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790554

RESUMEN

Purpose: Non-small cell lung cancer (NSCLC) is an aggressive tumor with high mortality and poor prognosis. In this study, we designed a liposome encapsulating polymeric micelles (PMs) loaded with vinorelbine (NVB) and cis-diamminedichloroplatinum (II) (cisplatin or CDDP) for the treatment of NSCLC. Materials and Methods: Sodium poly(α-l-glutamic acid)-graft-methoxy-polyethylene glycol (PLG-G-PEG5K) was used to prepare NVB-loaded NVB-PMs and CDDP-loaded CDDP-PMs that were co-encapsulated into liposomes by a reverse evaporation method, yielding NVB and CDDP co-delivery liposomes (CoNP-lips) composed of egg phosphatidyl lipid-80/cholesterol/DPPG/DSPE-mPEG2000 at a molar ratio of 52:32:14:2. The CoNP-lips were characterized in terms of particle size, zeta potential, drug content, encapsulation efficiency, and structural properties. Drug release by the CoNP-lips as well as their stability and cytotoxicity was evaluated in vitro, and their antitumor efficacy was assessed in a mouse xenograft model of Lewis lung carcinoma cell-derived tumors. Results: CoNP-lips had a spherical shape with uniform size distribution; the average particle size was 162.97±9.06 nm, and the average zeta potential was -13.02±0.22 mV. In vitro cytotoxicity analysis and the combination index demonstrated that the CoNP-lips achieved a synergistic cytotoxic effect at an NVB:CDDP weight ratio of 2:1 in an NSCLC cell line. There was sustained release of both drugs from CoNP-lips. The pharmacokinetic analysis showed that CoNP-lips had a higher plasma half-life than NP solution, with 6.52- and 8.03-fold larger areas under the receiver operating characteristic curves of NVB and CDDP. CoNP-lips showed antitumor efficacy in tumor-bearing C57BL/6 mice and drug accumulation in tumors via the enhanced permeability and retention effect. Conclusion: CoNP-lips are a promising formulation for targeted therapy in NSCLC.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/uso terapéutico , Sistemas de Liberación de Medicamentos , Neoplasias Pulmonares/tratamiento farmacológico , Micelas , Polímeros/química , Vinorelbina/uso terapéutico , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cisplatino/administración & dosificación , Cisplatino/farmacocinética , Cisplatino/farmacología , Liberación de Fármacos , Humanos , Liposomas , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos C57BL , Nanopartículas/ultraestructura , Tamaño de la Partícula , Polietilenglicoles/química , Ratas Sprague-Dawley , Distribución Tisular , Vinorelbina/farmacocinética , Vinorelbina/farmacología
6.
Int J Nanomedicine ; 16: 2373-2388, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790555

RESUMEN

Aim: The metastasis of breast cancer is an important cause of tumor recurrence. This study highlights that tyrosine kinase inhibitors dasatinib (DAS) and rosiglitazone (ROZ) inhibit tumor growth and reduce the occurrence of tumor cell metastasis. Due to the poor water solubility, short half-time in the body of DAS and ROZ, which increases the difficulty of tumor treatment, as well as the demand for nano-drug delivery systems for organ-specific therapies. Methods: Hyaluronic acid (HA) and DAS are bonded by a pH-sensitive ester bond to form an HA-DAS polymer. Then, ROZ was added as the core, D-A-tocopherol polydiethylene glycol isosuccinate (TPGS) and HA-DAS were used as carriers to form HA-DAS and TPGS mixed micelle system loaded with ROZ (THDR-NPs). The size and structure of THDR-NPs were characterized, the drug release, stability and biosafety of THDR-NPs were studied. In vitro, the cytotoxicity, targeting effect and tumor metastasis inhibition of THDR-NPs were evaluated in human breast cancer cell lines. In addition, the selective potency of designed THDR-NPs in depleting was further verified in vivo in the tumor-bearing nude mice model. Results: The designed THDR-NPs have a particle size of less than 100 nm, good stability, biological safety and sustained release, and showed strong therapeutic effects on breast cancer models in vitro and in vivo. Moreover, it has been proved that THDR-NPs have the ability to inhibit tumor metastasis. Conclusion: DAS and ROZ were designed into micelles, the efficacy of THDR-NPs was higher than that of free drugs. These results indicate that nanoparticles have a good application prospect in the treatment of tumor metastasis.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Animales , Peso Corporal/efectos de los fármacos , Neoplasias de la Mama/patología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Dasatinib/administración & dosificación , Dasatinib/farmacocinética , Dasatinib/farmacología , Dasatinib/uso terapéutico , Portadores de Fármacos/química , Liberación de Fármacos , Endocitosis/efectos de los fármacos , Femenino , Hemólisis/efectos de los fármacos , Humanos , Ácido Hialurónico/química , Ratones Endogámicos BALB C , Ratones Desnudos , Micelas , Nanopartículas/química , Nanopartículas/ultraestructura , Tamaño de la Partícula , Espectroscopía de Protones por Resonancia Magnética , Ratas Sprague-Dawley , Rosiglitazona/farmacocinética , Rosiglitazona/farmacología , Rosiglitazona/uso terapéutico , Electricidad Estática , Distribución Tisular/efectos de los fármacos , Carga Tumoral/efectos de los fármacos
7.
Int J Nanomedicine ; 16: 2389-2404, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790556

RESUMEN

Recently, there has been an incredible increase in research about the abnormal growth of cells (neoplasm), focusing on the management, treatment and preventing reoccurrence. It has been understood that the natural defense system, composed of a variety of immune defensive cells, does not just limit its function in eliminating neoplastic cells, but also controls the growth and spread of tumor cells of different kinds to other parts of the body. Cancer immunotherapy, is a cancer treatment plan that educates the body's defensive system to forestall, control, and eliminate tumor cells. The effectiveness of immunotherapy is achieved, to its highest efficacy, by the use of nanoparticles (NPs) for precise and timely delivery of immunotherapies to specific targeted neoplasms, with less or no harm to the healthy cells. Immunotherapies have been affirmed in clinical trials as a cancer regimen for various types of cancers, the side effects resulting from imprecise and non-targeted conveyance is well managed with the use of nanoparticles. Nonetheless, we will concentrate on enhancing cancer immunotherapy approaches by the use of nanoparticles for the productivity of antitumor immunity. Nanoparticles will be presented and utilized as an objective immunotherapy delivery system for high exactness and are thus a promising methodology for cancer treatment.


Asunto(s)
Sistemas de Liberación de Medicamentos , Objetivos , Inmunoterapia , Nanopartículas/química , Neoplasias/inmunología , Neoplasias/terapia , Animales , Humanos , Nanopartículas/administración & dosificación
8.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33802169

RESUMEN

In order to treat Coronavirus Disease 2019 (COVID-19), we predicted and implemented a drug delivery system (DDS) that can provide stable drug delivery through a computational approach including a clustering algorithm and the Schrödinger software. Six carrier candidates were derived by the proposed method that could find molecules meeting the predefined conditions using the molecular structure and its functional group positional information. Then, just one compound named glycyrrhizin was selected as a candidate for drug delivery through the Schrödinger software. Using glycyrrhizin, nafamostat mesilate (NM), which is known for its efficacy, was converted into micelle nanoparticles (NPs) to improve drug stability and to effectively treat COVID-19. The spherical particle morphology was confirmed by transmission electron microscopy (TEM), and the particle size and stability of 300-400 nm were evaluated by measuring DLSand the zeta potential. The loading of NM was confirmed to be more than 90% efficient using the UV spectrum.


Asunto(s)
/tratamiento farmacológico , Biología Computacional/métodos , Sistemas de Liberación de Medicamentos/métodos , Células A549 , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Benzamidinas/química , Benzamidinas/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Análisis por Conglomerados , Simulación por Computador , Bases de Datos Farmacéuticas , Portadores de Fármacos/química , Reposicionamiento de Medicamentos , Estabilidad de Medicamentos , Ácido Glicirrínico/química , Ácido Glicirrínico/uso terapéutico , Guanidinas/química , Guanidinas/uso terapéutico , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Micelas , Microscopía Electrónica de Transmisión , Estructura Molecular , Nanopartículas/química , Tamaño de la Partícula
9.
Int J Nanomedicine ; 16: 2419-2441, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33814908

RESUMEN

Lignin is an abundant renewable natural biopolymer. Moreover, a significant development in lignin pretreatment and processing technologies has opened a new window to explore lignin and lignin-based bionanomaterials. In the last decade, lignin has been widely explored in different applications such as drug and gene delivery, tissue engineering, food science, water purification, biofuels, environmental, pharmaceuticals, nutraceutical, catalysis, and other interesting low-value-added energy applications. The complex nature and antioxidant, antimicrobial, and biocompatibility of lignin attracted its use in various biomedical applications because of ease of functionalization, availability of diverse functional sites, tunable physicochemical and mechanical properties. In addition to it, its diverse properties such as reactivity towards oxygen radical, metal chelation, renewable nature, biodegradability, favorable interaction with cells, nature to mimic the extracellular environment, and ease of nanoparticles preparation make it a very interesting material for biomedical use. Tremendous progress has been made in drug delivery and tissue engineering in recent years. However, still, it remains challenging to identify an ideal and compatible nanomaterial for biomedical applications. In this review, recent progress of lignin towards biomedical applications especially in drug delivery and in tissue engineering along with challenges, future possibilities have been comprehensively reviewed.


Asunto(s)
Sistemas de Liberación de Medicamentos , Técnicas de Transferencia de Gen , Lignina/química , Ingeniería de Tejidos , Animales , Biomasa , Humanos , Nanopartículas/química , Nanopartículas/ultraestructura
10.
Int J Nanomedicine ; 16: 2443-2459, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33814909

RESUMEN

Background: Specific modifications to carriers to achieve targeted delivery of chemotherapeutics into malignant tissues are a critical point for efficient diagnosis and therapy. In this case, bovine serum albumin (BSA) was conjugated with cetuximab-valine-citrulline (vc)-doxorubicin (DOX) to target epidermal growth factor receptor (EGFR) and enable the release of drug in EGFR-overexpressed tumor cells. Methods: Maleimidocaproyl-valine-citrulline-p-aminobenzylcarbonyl-p-nitrophenol (MC-Val-Cit-PAB-PNP) and DOX were used to synthesize MC-Val-Cit-PAB-DOX, which was further linked with cetuximab to prepare antibody-drug conjugates (ADCs). Then, the ADCs were adsorbed to the surface of the BSA nanoparticles (NPs), which were prepared by a desolvation method to obtain cetuximab-vc-DOX-BSA-NPs. The cetuximab-vc-DOX conjugates adsorbed on the surface of the BSA nanoparticles were determined and optimized by size exclusion chromatography. An in vitro cytotoxicity study was conducted using a colon carcinoma cell line with different EGFR-expression levels to test the selectivity of cetuximab-vc-DOX-NPs. Results: The vc-DOX and cetuximab-vc-DOX conjugates were both synthesized successfully and their structural characteristics confirmed by 1H-NMR and SDS-PAGE. The MTT assay showed stronger cytotoxicity of cetuximab-vc-DOX-NPs versus control IgG-vc-DOX-NPs in EGFR-overexpressing RKO cells. Cellular binding and intracellular accumulation determined by flow cytometry and confocal laser scanning microscopy revealed the strong binding ability of cetuximab-vc-DOX-NPs to RKO cells. The in vivo imaging study demonstrated that cetuximab-vc-DOX-NPs exhibited higher fluorescent intensity in tumor tissues than non-decorated nanoparticles (IgG-vc-DOX-NPs). In vivo tumor inhibition and survival tests showed that cetuximab-vc-DOX-NPs revealed higher tumor inhibition efficacy and lower systemic toxicity than control IgG-vc-DOX- NPs. Conclusion: The obtained results emphasize that cetuximab-vc-DOX-NPs, with good tumor-targeting ability and low systemic toxicity, are a promising targeting system for drug delivery.


Asunto(s)
Cetuximab/uso terapéutico , Citrulina/química , Neoplasias Colorrectales/tratamiento farmacológico , Doxorrubicina/uso terapéutico , Receptores ErbB/metabolismo , Nanopartículas/química , Albúmina Sérica Bovina/química , Valina/química , Adsorción , Animales , Bovinos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos/métodos , Endocitosis/efectos de los fármacos , Humanos , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Ratones , Tamaño de la Partícula , Espectroscopía de Protones por Resonancia Magnética , Distribución Tisular/efectos de los fármacos
11.
Int J Nanomedicine ; 16: 2477-2486, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33824586

RESUMEN

Purpose: Sensitive and selective point-of-care biosensor is an urgent pursuit of serological antibody detection to control parasite pathogen. For specific, quantitative and on-site screening of Trichinella spiralis infection in livestock, a quantum dot nanobead-monoclonal antibody (QB-mAb) probe-based immunochromatographic assay (ICA) was developed by introducing a competitive sandwich strategy (QB-CICA). Methods: In the QB-CICA, QB-mAb probes competed with serum antibody for a particular epitope, followed by immunocomplexes binding to capture antibody on the test line. With the accumulation of target antibody, captured probes served as signal elements for fluorescent readout in a "turn off" mode, along with the fluorescence gradually weakened. The sensitivity and standard calibration curve of the QB-CICA were quantified using swine sera as negative control (n = 200) and artificial infected swine sera (n = 80) compared with a commercial ELISA kit. Besides, Trichinella spiralis-antibody targeting test ability of the QB-CICA, instead of other parasites or viruses antibodies (n = 10), was evaluated. Results: The QB-CICA exhibited a good linear range, a low detection limit of 189.92 ng mL-1 and 100% selectivity that was higher than commercial ELISA kit (90%), as well as the same serological positive rate (100%) with commercial ELISA kit in different infection dose models. Conclusion: Taking advantage of its simplicity, short response time (25 min), sensitivity and specificity, the proposed QB-CICA has potential applications for parasite-related antibody monitoring in food safety and clinical diagnosis fields.


Asunto(s)
Anticuerpos Antihelmínticos/análisis , Anticuerpos Monoclonales/inmunología , Cromatografía de Afinidad/métodos , Nanopartículas/química , Puntos Cuánticos/química , Trichinella spiralis/inmunología , Triquinelosis/diagnóstico , Triquinelosis/inmunología , Animales , Anticuerpos Antihelmínticos/sangre , Anticuerpos Antihelmínticos/inmunología , Nanopartículas/ultraestructura , Puntos Cuánticos/ultraestructura , Porcinos , Triquinelosis/parasitología
12.
Int J Nanomedicine ; 16: 2487-2499, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33824587

RESUMEN

Purpose: Due to the shortcomings of nanocarriers, the development of carrier-free nanodelivery systems has attracted more and more attention in cancer treatment. However, there are few studies on carrier-free nanosystems that can simultaneously achieve monitoring functions. Here a multifunctional carrier-free nanosystem loaded with curcumin and irinotecan hydrochloride was established for the treatment and monitoring of gastric cancer. Methods: In this study, an irinotecan hydrochloride-curcumin nanosystem in the early stage (the system is named SICN) was prepared. Based on the fluorescence of curcumin, flow cytometry, laser confocal microscopy, and zebrafish fluorescence imaging were used to study the monitoring function of SICN in vivo and in vitro. In addition, HGC-27 human gastric cancer cells were used to study SICN cytotoxicity. Results: Flow cytometry and zebrafish fluorescence imaging monitoring results showed that the uptake of SICN was significantly higher than free curcumin, and the excretion rate was lower. SICN had higher accumulation and retention in cells and zebrafish. Laser confocal microscopy monitoring results showed that SICN was internalized into HGC-27 cells through multiple pathways, including macropinocytosis, caveolin, and clathrin-mediated and clathrin -independent endocytosis, and distributed intracellularly throughout the whole cytoplasm, including lysosomes and Golgi apparatus. In vitro cell experiments showed that SICN nanoparticles were more toxic than single components, and HGC-27 cells had more absorption and higher toxicity to nanoparticles under slightly acidic conditions. Conclusion: SICN is a promising carrier-free nanoparticle, and the combination of two single-component therapies can exert a synergistic antitumor effect. When exposed to a tumor acidic environment, SICN showed stronger cytotoxicity due to charge conversion. More importantly, the nanoparticles' self-monitoring function has been developed, opening up new ideas for combined tumor therapy.


Asunto(s)
Sistemas de Liberación de Medicamentos , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Curcumina/administración & dosificación , Curcumina/farmacología , Curcumina/uso terapéutico , Portadores de Fármacos , Liberación de Fármacos , Endocitosis/efectos de los fármacos , Fluorescencia , Humanos , Imagenología Tridimensional , Irinotecán/farmacología , Irinotecán/uso terapéutico , Tamaño de la Partícula , Pez Cebra
13.
Int J Nanomedicine ; 16: 2501-2513, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33824588

RESUMEN

Introduction: Aim to obtain a NO donor that can control released NO in vivo with the high efficacy of tumor suppression and targeting, a nanoplatform consisting of FA-Fe3O4@mSiO2-Au/DOX was constructed. Methods: In vitro, the nanoplatform catalyzed NO's release with the maximum value of 4.91 µM within 60 min at 43°C pH=5.0, which was increased by 1.14 times when the temperature was 37°C. In vivo, 11.7 µg Au in the tumor tissue was found to catalyze S-nitrosoglutathione continuously, and 54 µM NO was checked out in the urine. Results and Discussion: The high concentration of NO was found to increase the apoptotic rate and to reduce tumor proliferation. In the chemo-photothermal combination therapy, the tumor inhibition rate was increased up to 94.3%, and Au's contribution from catalyzing NO release NO was 8.17%.


Asunto(s)
Oro/química , Neoplasias/patología , Neoplasias/terapia , Óxido Nítrico/metabolismo , Catálisis , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Liberación de Fármacos , Endocitosis/efectos de los fármacos , Ácido Fólico/química , Humanos , Células MCF-7 , Fenómenos Magnéticos , Nanopartículas/química , Nanopartículas/ultraestructura , Tamaño de la Partícula , Porosidad , Silicio/química , Difracción de Rayos X
14.
Int J Nanomedicine ; 16: 2533-2553, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33824590

RESUMEN

Purpose: The present study was intended to fabricate chitosan (Ch)-tamarind gum polysaccharide (TGP) polyelectrolyte complex stabilized cubic nanoparticles of simvastatin and evaluate their potential against human breast cancer cell lines. Materials and Methods: The antisolvent precipitation method was used for formulation of nanoparticles. Factorial design (32) was utilized as a tool to analyze the effect of Ch and TGP concentration on particle size and entrapment efficiency of nanoparticles. Results: Formulated nanoparticles showed high entrapment efficiency (67.19±0.42-83.36±0.23%) and small size (53.3-383.1 nm). The present investigation involved utilization of two biological membranes (egg and tomato) as biological barriers for drug release. The study revealed that drug release from tomato membranes was retarded (as compared to egg membranes) but the release pattern matched that of egg membranes. All formulations followed the Baker-Lansdale model of drug release irrespective of the two different biological barriers. Stability studies were carried out for 45 days and exhibited less variation in particle size as well as a reduction in entrapment efficiency. Simvastatin loaded PEC stabilized nanoparticles exhibited better control on growth of human breast cancer cell lines than simple simvastatin. An unusual anticancer effect of simvastatin nanoparticles is also supported by several other research studies. Conclusion: The present study involves first-time synthesis of Ch-TGP polyelectrolyte complex stabilized nanoparticles of simvastatin against MCF-7 cells. It recommends that, in future, theoretical modeling and IVIVC should be carried out for perfect designing of delivery systems.


Asunto(s)
Quitosano/química , Nanopartículas/química , Gomas de Plantas/química , Polielectrolitos/química , Polisacáridos/química , Simvastatina/farmacología , Tamarindus/química , Antineoplásicos/farmacología , Muerte Celular/efectos de los fármacos , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Humanos , Células MCF-7 , Nanopartículas/ultraestructura , Tamaño de la Partícula , Espectrofotometría Infrarroja , Electricidad Estática
15.
Adv Exp Med Biol ; 1310: 115-132, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33834435

RESUMEN

Various silica-based fluorescent nanoparticles ((Si-FNP)) with magnetic or metal cores represent a standard class of nanoparticles offering new opportunities for high-resolution cellular imaging and biomedicine applications, such as drug delivery. Their high solubility, homogeneity, biocompatibility, and chemical inertness Si-FNPs make them attractive probes for correlative light and electron microscopy (CLEM) studies, offering novel insights into nanoparticle-cell interactions in detail. In the present chapter, we present a procedure for imaging silica-based fluorescent magnetic core-shell nanoparticles (Si-FMNP) at the single-particle scale in cells. Our method facilitates the acquisition of information on the extracellular and intercellular distribution of nanoparticles and their various interactions with various cellular organelles when cells are cultured and electroporated by NPs. In addition, such information could facilitate the evaluation of the efficacy of nanocarriers designed for drug delivery.


Asunto(s)
Nanopartículas , Comunicación Celular , Sistemas de Liberación de Medicamentos , Microscopía Electrónica , Dióxido de Silicio
16.
Adv Exp Med Biol ; 1310: 401-447, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33834444

RESUMEN

Nanotechnology has been widely applied to medical interventions for prevention, diagnostics, and therapeutics of diseases, and the application of nanotechnology for medical purposes, which is called as a term "nanomedicine" has received tremendous attention. In particular, the design and development of nanoparticle for biosensors have received a great deal of attention, since those are most impactful area of clinical translation showing potential breakthrough in early diagnosis of diseases such as cancers and infections. For example, the nanoparticles that have intrinsic unique features such as magnetic responsive characteristics or photoluminescence can be utilized for noninvasive visualization of inner body. Drug delivery that makes use of drug-containing nanoparticles as a carrier is another field of study, in which the particulate form nanomedicine is given by parenteral administration for further systemic targeting to pathological tissues. In addition, encapsulation into nanoparticles gives the opportunity to secure the sensitive therapeutic payloads that are readily degraded or deactivated until reached to the target in biological environments, or to provide sufficient solubilization (e.g., to deliver compounds which have physicochemical properties that strongly limit their aqueous solubility and therefore systemic bioavailability). The nanomedicine is further intended to enhance the targeting index such as increased specificity and reduced false binding, thus improve the diagnostic and therapeutic performances. In this chapter, principles of nanomaterials for medicine will be thoroughly covered with applications for imaging-based diagnostics and therapeutics.


Asunto(s)
Nanopartículas , Neoplasias , Sistemas de Liberación de Medicamentos , Humanos , Nanomedicina , Nanotecnología , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico
17.
Nat Commun ; 12(1): 2077, 2021 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-33824321

RESUMEN

Aggregation-induced emission (AIE) has, since its discovery, become a valuable tool in the field of nanoscience. AIEgenic molecules, which display highly stable fluorescence in an assembled state, have applications in various biomedical fields-including photodynamic therapy. Engineering structure-inherent, AIEgenic nanomaterials with motile properties is, however, still an unexplored frontier in the evolution of this potent technology. Here, we present phototactic/phototherapeutic nanomotors where biodegradable block copolymers decorated with AIE motifs can transduce radiant energy into motion and enhance thermophoretic motility driven by an asymmetric Au nanoshell. The hybrid nanomotors can harness two photon near-infrared radiation, triggering autonomous propulsion and simultaneous phototherapeutic generation of reactive oxygen species. The potential of these nanomotors to be applied in photodynamic therapy is demonstrated in vitro, where near-infrared light directed motion and reactive oxygen species induction synergistically enhance efficacy with a high level of spatial control.


Asunto(s)
Luz , Nanopartículas/química , Fototerapia , Línea Celular Tumoral , Oro/química , Células HeLa , Humanos , Movimiento (Física) , Nanopartículas/ultraestructura , Polímeros/química
18.
Water Sci Technol ; 83(7): 1591-1604, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33843745

RESUMEN

Dairy plants produce 1 to 4 L of wastewater per 1 L of processed milk. The wastewater contains high values of chemical oxygen demand (COD) and biochemical oxygen demand (BOD) concentrations, in addition to high levels of dissolved solids. In this study, synthesized copper oxide nanoparticles (CuONPs) coupled with Sophora Japonica fruit, were used as an adsorbent, for the first time, to treat the effluent of dairy plants in a batch adsorption process. The analysis techniques, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were utilized to characterize the adsorbent. The COD removal, using (CuONPs)-based adsorbent, was investigated by varying contact time, masses of the adsorbent, initial COD value and temperatures. The optimum conditions for highest removal percentage were contact time of 120 min, a temperature of 25 °C, pH value of 7.5, and 1 g of adsorbent. The initial COD values used were in the range of 100-700 ppm. The COD percent removal was in the range of 77 to 95%. Freundlich isotherm exhibited the best fitting for the results (R2 = 0.998) with a favorable spontaneous exothermic adsorption process. Based on the calculated normalized deviation value, the modified diffusion model, intra-diffusion, and pseudo-second-order kinetics all showed very good fitting for the adsorption data as indicated by the kinetics study.


Asunto(s)
Nanopartículas , Contaminantes Químicos del Agua , Adsorción , Cobre , Concentración de Iones de Hidrógeno , Cinética , Óxidos , Espectroscopía Infrarroja por Transformada de Fourier , Termodinámica , Aguas Residuales
19.
Water Sci Technol ; 83(7): 1739-1752, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33843756

RESUMEN

An exceedingly facile green approach that produces a reliable adsorbent based on a transition metal such as Iron (Fe) using Mangifera indica leaf extract at room temperature is described. A single pot method was used for synthesis with no capping agents, surfactants or other templates. The main intention of this study is to synthesize iron nanoparticles from leaf extract (Mangifera indica) and examine its degradation potential for photo-catalytic removal of dyes (Congo red and brilliant green) from wastewater. Characterization of synthesized nanoparticles was executed by pHpzc, scanning electron microscopy and Fourier transform infrared spectroscopy studies and results confirm the presence of iron nano-sheets with biomolecules. All photo-catalytic experimental results were assessed by sum of squared estimate of errors and simple linear regression R2 with dye concentration, pH, contact time and dose rate as dependent and independent variables. Adsorption experimental data was verified by kinetics and isothermal models. Results showed that Langmuir and pseudo second order models give best fitness towards the photo-catalytic adsorption procedure. Thermodynamics revealed that adsorption mechanism is endothermic, described by the values of changes in Gibbs free energy, enthalpy and entropy, and is chemisorption in nature, with spontaneous processes. Overall photo-catalytic adsorption execution with synthesized iron nanoparticles and simple biomass of Mangifera indica gives satisfactory results for treating dye wastewater.


Asunto(s)
Nanopartículas , Contaminantes Químicos del Agua , Adsorción , Colorantes , Concentración de Iones de Hidrógeno , Cinética , Extractos Vegetales , Espectroscopía Infrarroja por Transformada de Fourier , Termodinámica
20.
Artif Cells Nanomed Biotechnol ; 49(1): 204-218, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33645342

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoo tonic, highly pathogenic virus. The new type of coronavirus with contagious nature spread from Wuhan (China) to the whole world in a very short time and caused the new coronavirus disease (COVID-19). COVID-19 has turned into a global public health crisis due to spreading by close person-to-person contact with high transmission capacity. Thus, research about the treatment of the damages caused by the virus or prevention from infection increases everyday. Besides, there is still no approved and definitive, standardized treatment for COVID-19. However, this disaster experienced by human beings has made us realize the significance of having a system ready for use to prevent humanity from viral attacks without wasting time. As is known, nanocarriers can be targeted to the desired cells in vitro and in vivo. The nano-carrier system targeting a specific protein, containing the enzyme inhibiting the action of the virus can be developed. The system can be used by simple modifications when we encounter another virus epidemic in the future. In this review, we present a potential treatment method consisting of a nanoparticle-ribozyme conjugate, targeting ACE-2 receptors by reviewing the virus-associated ribozymes, their structures, types and working mechanisms.


Asunto(s)
/tratamiento farmacológico , Nanopartículas/administración & dosificación , ARN Catalítico/uso terapéutico , ARN Viral/antagonistas & inhibidores , /efectos de los fármacos , /antagonistas & inhibidores , Ensayos Clínicos como Asunto , Portadores de Fármacos , Composición de Medicamentos , Diseño de Fármacos , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Modelos Moleculares , Conformación de Ácido Nucleico , Interferencia de ARN , ARN Catalítico/administración & dosificación , ARN Catalítico/química , ARN Catalítico/clasificación , ARN no Traducido/clasificación , ARN no Traducido/genética , ARN no Traducido/uso terapéutico , Virus del SRAS/efectos de los fármacos , Virus del SRAS/genética , /fisiología , Glicoproteína de la Espiga del Coronavirus/fisiología , Replicación Viral/efectos de los fármacos
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