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1.
J Biomed Mater Res A ; 112(5): 733-742, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38088136

RESUMO

Among all the cancers, colorectal cancer (CRC) has the third mortality rank in both genders. Cancer vaccines have shown promising results in boosting patients' immune systems to fight cancer. Using the IEDB database, we predicted mouse MHC-I (H2-Ld) binding epitopes from four tumor-associated antigens (APC, KRAS, TP53, and PIK3CA) and designed a multi-epitope vaccine. We expressed the candidate vaccine and encapsulated it into the cationic micelle with polyethyleneimine conjugated to oleic acid as its building blocks. We studied tumor inhibition effect, cytokine production, and lymphocyte proliferation in the mouse CRC model after vaccination. Our finding illustrated significant tumor growth inhibition in mouse models treated with the candidate nanovaccine. Besides the significant release of IFN-γ and IL-4 by immunized mouse spleen T-lymphocytes, T-cell proliferation assay results confirmed effective immune response after the vaccination. These results demonstrate the potential therapeutic effects of nanovaccines and could be a possible approach to CRC immunotherapy.


Assuntos
Vacinas Anticâncer , Neoplasias Colorretais , Masculino , Humanos , Feminino , Animais , Camundongos , Epitopos , Micelas , Antígenos de Neoplasias , Neoplasias Colorretais/terapia , Ativação Linfocitária
2.
Sci Rep ; 13(1): 15131, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37704633

RESUMO

To solve the traditional radiotherapy obstacles, and also to enhance the radiation therapy efficacy various radiosensitizers have been developed. Radiosensitizers are promising agents that under X-ray irradiation enhance injury to tumor tissue by accelerating DNA damage. In this report, silver-silver sulfide nanoparticles (Ag-Ag2S NPs) were synthesized via a facile, one-pot and environmentally friendly biomineralization method. Ag-Ag2S was coated with bovine serum albumin (BSA) in situ and applied as an X-ray sensitizer to enhance the efficiency of radiotherapy. Also, folic acid (FA) was conjugated to Ag-Ag2S@BSA to impart active targeting capability to the final formulation (Ag-Ag2S@BSA-FA). Prepared NPs were characterized by transmission electron microscopes (TEM), scanning electron microscope (SEM), dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), X-ray diffraction analysis (XRD), and X-ray photoelectron spectroscopy (XPS) techniques. Results show that most of the NPs have well-defined uniform Janus structures. The biocompatibility of the NPs was then evaluated both in vitro and in vivo. A series of in vitro assays were performed on 4T1 cancer cells to evaluate the therapeutic efficacy of the designed NPs. In addition, the radio-enhancing ability of the NPs was tested on the 4T1 breast cancer murine model. MTT, live and dead cell staining, apoptosis, ROS generation, and clonogenic in vitro assays demonstrated the efficacy of NPs as radiosensitizers in radiotherapy. In vivo results as well as H&E staining tumor tissues confirmed tumor destruction in the group that received Ag-Ag2S@BSA-FA NPs and exposed to X-ray. The results showed that prepared tumor-targeted Ag-Ag2S@BSA-FA NPs could be potential candidates as radiosensitizers for enhanced radiotherapy.


Assuntos
Neoplasias , Radioterapia (Especialidade) , Radiossensibilizantes , Animais , Camundongos , Prata/farmacologia , Biomineralização , Radiossensibilizantes/farmacologia , Projetos de Pesquisa , Ácido Fólico
3.
Mikrochim Acta ; 190(5): 184, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37069457

RESUMO

In recent years, various types of radiosensitizers have been developed to address the challenges of cancer radiotherapy. Here, platinum-functionalized oxygenated single-walled carbon nanotubes (O-SWCNTs-Pt) coated with folic acid (FA) and bovine serum albumin (BSA) (O-SWCNTs-Pt-BSA-FA) were synthesized, characterized, and used as radiosensitizers to improve the therapeutic efficacy of X-rays in a mouse model of breast cancer (4T1) in vitro. The nanosensitizer was characterized by different techniques, such as transmission electron microscopy (TEM), selected area electron diffraction (SAED), dynamic light scattering (DLS), zeta potential, X-ray diffraction (XRD), ultraviolet-visible (UV-visible), and Fourier transform infrared (FTIR) spectrometry. The evaluation of cell viability with nanocarriers O-SWCNTs-BSA, O-SWCNTs-Pt-BSA, Pt-BSA-FA, and O-SWCNTs-Pt-BSA-FA is reported at the concentrations of 10, 30, and 90 µg/mL by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in the presence and absence of X-rays at 4 and 8 Gy. The results showed that administration of O-SWCNTs-BSA, O-SWCNTs-Pt-BSA, Pt-BSA-FA, and O-SWCNTs-Pt-BSA-FA + 8 Gy at a concentration of 90 µg/mL reduced survival by 75.31, 65.32, 67.35, and 60.35%, respectively. O-SWCNTs-Pt-BSA-FA has a hydrodynamic size of 88.57 nm and a surface charge of -29 mV, which indicates special stability. Compared with O-SWCNTs-BSA, O-SWCNTs-Pt-BSA, and Pt-BSA-FA, it has very strong cell-killing activity in the 4T1 cell line. It is also noteworthy that SWCNTs can act as a controlled release and delivery system for PtNPs due to their unique properties and easy penetration into biological membranes. As a result, the  new nanosensitizer may play a role in cancer treatment in conjunction with radiotherapy technology. Graphical abstract.


Assuntos
Nanopartículas Metálicas , Nanotubos de Carbono , Neoplasias , Animais , Camundongos , Nanotubos de Carbono/química , Platina , Raios X , Linhagem Celular , Soroalbumina Bovina/química , Neoplasias/tratamento farmacológico
4.
Heliyon ; 9(3): e13874, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36895357

RESUMO

Despite the over spatial separation and the ability to determine soft tissues, insufficient contrast is the shortcoming of magnetic resonance imaging (MRI) that could be circumvented by the use of contrast agents. The use of MRI contrast agents are widely applied to enhance the vision of internal body structures. Nano-sized contrast materials have unique application advantages compared to other contrast agents due to their size and shape. However, for contrast agents such as bare iron (II, III) oxide (Fe3O4) magnetic nanoparticles (NPs), aggregation and accumulation are the main shortcomings. Thus, surface modifications are necessary for their use in biopharmaceutical applications. Gold, Au, nanoparticles are of big interesting for use in biomedical purposes due to their chemical stability and oxidation resistance. In this study, we synthesized magnetic Fe3O4-Au hybrid NPs with a facile method and coated them with bovine serum albumin (BSA) to increase their chemical stability and biocompatibility. Afterwards, the hybrid nanosystem was characterized by some methods, and their potential to increase MRI contrast was investigated by the phantom MRI experiments. Our data showed that the signal intensity on MR images was significantly reduced, thus confirming the contrast ability of the formulated Fe3O4-Au-BSA NPs.

5.
J Biomater Sci Polym Ed ; 34(13): 1824-1842, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36869798

RESUMO

Application of conventional chemotherapy regardless of its unique effectiveness have been gradually being edged aside due to limited targeting capability, lack of selectivity and chemotherapy-associated side effects. To this end, colon-targeted nanoparticles via combination therapy have shown great therapeutic potential against cancer. Herein, pH/enzyme-responsive biocompatible polymeric nanohydrogels based on poly(methacrylic acid) (PMAA) containing methotrexate (MTX) and chloroquine (CQ) were fabricated. PMAA-MTX-CQ exhibited high drug loading capacity of which MTX was 4.99% and was CQ 25.01% and displayed pH/enzyme-triggered drug release behavior. Higher CQ release rate (76%) under simulated acidic microenvironment of tumor tissue whereas 39% of CQ was released under normal physiological conditions. Intestinally, MTX release was facilitated in the presence of proteinase K enzyme. TEM image demonstrated spherical morphology with particle size of less than 50 nm. In vitro and in vivo toxicity assessments indicated that developed nanoplatforms possessed great biocompatibility. These nanohydrogels did not cause any adverse effects against Artemia Salina and HFF2 cells (around 100% cell viability) which highlight the safety of prepared nanohydrogels. There was no death in mice received different concentrations of nanohydrogel through oral administration and less than 5% hemolysis was found in red blood cells incubated with PMAA nanohydrogels. In vitro anti-cancer results showed that combination therapy based on PMAA-MTX-CQ can effectively suppress the growth of SW480 colon cancer cells (29% cell viability) compared to monotherapy. Altogether, these findings suggest that pH/enzyme-responsive PMAA-MTX-CQ could effectively inhibit cancer cell growth and progression via site-specific delivery of its cargo in a safe and controlled manner.


Assuntos
Neoplasias Colorretais , Nanopartículas , Camundongos , Animais , Metotrexato/farmacologia , Cloroquina/farmacologia , Polímeros , Sistemas de Liberação de Medicamentos/métodos , Concentração de Íons de Hidrogênio , Neoplasias Colorretais/tratamento farmacológico , Microambiente Tumoral
6.
Oxid Med Cell Longev ; 2023: 7643280, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36865347

RESUMO

Ischemic stroke is the most common among various stroke types and the second leading cause of death, worldwide. Edaravone (EDV) is one of the cardinal antioxidants that is capable of scavenging reactive oxygen species, especially hydroxyl molecules, and has been already used for ischemic stroke treatment. However, poor water solubility, low stability, and bioavailability in aqueous media are major EDV drawbacks. Thus, to overcome the aforementioned drawbacks, nanogel was exploited as a drug carrier of EDV. Furthermore, decorating the nanogel surface with glutathione as targeting ligands would potentiate the therapeutic efficacy. Nanovehicle characterization was assessed with various analytical techniques. Size (199 nm, hydrodynamic diameter) and zeta potential (-25 mV) of optimum formulation were assessed. The outcome demonstrated a diameter of around 100 nm, sphere shape, and homogenous morphology. Encapsulation efficiency and drug loading were determined to be 99.9% and 37.5%, respectively. In vitro drug release profile depicted a sustained release process. EDV and glutathione presence in one vehicle simultaneously made the possibility of antioxidant effects on the brain in specific doses, which resulted in elevated spatial memory and learning along with cognitive function in Wistar rats. In addition, significantly lower MDA and PCO and higher levels of neural GSH and antioxidant levels were observed, while histopathological improvement was approved. The developed nanogel can be a suited vehicle for drug delivery of EDV to the brain and improve ischemia-induced oxidative stress cell damage.


Assuntos
AVC Isquêmico , Neuroproteção , Ratos , Animais , Ratos Wistar , Edaravone/farmacologia , Edaravone/uso terapêutico , Nanogéis , Encéfalo , Glutationa , Isquemia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doença Aguda
7.
Int J Biol Macromol ; 234: 123636, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36775221

RESUMO

A wide range of high-Z nanomaterials are fabricated to decrease radiation dose by sensitizing cells to irradiation through various mechanisms such as ROS generation enhancement. Alginate-coated silver sulfide nanoparticles (Ag2S@Alg) were synthesized and characterized by SEM, TEM, DLS, XRD, EPS, FT-IR, and UV-vis analysis techniques. Cytotoxicity of nanoparticles was tested against HFF-2, MCF-7, and 4 T1 cell lines for biocompatibility and radio enhancement ability evaluation, respectively. Moreover, the hemolysis assay demonstrated that the nanoparticles were biocompatible and nontoxic. In vitro intracellular ROS generation and calcein AM/PI co-staining unveiled cancerous cell death induction by nanoradiosensitizer, Ag2S@Alg. Further, histopathology results emphasized the tumor ablation capability of Ag2S@Alg. Silver anticancer properties were also recognized and combined with its radiosensitizing effect under X-ray irradiation.


Assuntos
Neoplasias da Mama , Nanopartículas Metálicas , Humanos , Feminino , Alginatos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/patologia , Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Espécies Reativas de Oxigênio , Nanopartículas Metálicas/uso terapêutico
8.
Heliyon ; 9(2): e13740, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36852040

RESUMO

Cancer is among the most common causes of death in the world that affects a large number of people every year. Curcumin is one of the natural anticancer therapeutics with little or no negative effects. However, due to its hydrophobic nature, poor bioavailability, limited gastrointestinal uptake, and fast metabolism, its therapeutic applications are constrained. Therefore, the Bovine Serum Albumin-Coated Copper Sulfide anoparticles (CuS@BSA) for curcumin (CUR) drug delivery were synthesized and characterized, and then curcumin release from the nanosystem. Hemotoxicity, and cytotoxicity was investigated. This study involved the one-step synthesis of CuS@BSA nanoparticles first, followed by the addition of CUR. Then the synthesized nanoparticles were characterized employing Scanning Transient Electron Microscopy (STEM), Ultraviolet-visible spectroscopy (UV-vis) and Fourier-transform infrared spectroscopy (FT-IR) techniques. The Size and surface charge (zeta potential) of synthesized nanoparticles were determined by Dynamic Light Scattering (DLS) to be 120 nm and -13 eV, respectively. The results showed that the CUR loading was around 15% and also the release pattern of CUR was dependent on pH and increased in an acidic environment. The results of the hemolysis assay showed that the synthesized nanoparticles are not hemotoxic. The investigation of the cytotoxic effects of synthesized nanoparticles on cancer cells demonstrated that CuS@BSA nanoparticles did not exhibit any toxicity and therefore are an appropriate candidate for drug delivery.

9.
J Control Release ; 353: 850-863, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36493951

RESUMO

Multifunctional nanoplatforms based on novel bimetallic nanoparticles have emerged as effective radiosensitizers owing to their potential capability in cancer cells radiosensitization. Implementation of chemotherapy along with radiotherapy, known as synchronous chemoradiotherapy, can augment the treatment efficacy. Herein, a tumor targeted nanoradiosensitizer with synchronous chemoradiotion properties, termed as CuFe2O4@BSA-FA-CUR, loaded with curcumin (CUR) and modified by bovine serum albumin (BSA) and folic acid (FA) was developed to enhance tumor accumulation and promote the anti-cancer activity while attenuating adverse effects. Both copper (Cu) and iron (Fe) were utilized in the construction of these submicron scale entities, therefore strong radiosensitization effect is anticipated by implementation of these two metals. The structure-function relationships between constituents of nanomaterials and their function led to the development of nanoscale materials with great radiosensitizing capacity and biosafety. BSA was used to anchor Fe and Cu ions but also to improve colloidal stability, blood circulation time, biocompatibility, and further functionalization. Moreover, to specifically target tumor sites and enhance cellular uptake, FA was conjugated onto the surface of hybrid bimetallic nanoparticles. Finally, CUR as a natural chemotherapeutic agent was encapsulated into the developed bimetallic nanoparticles. With incorporation of all abovementioned stages into one multifunctional nanoplatform, CuFe2O4@BSA-FA-CUR is produced for synergistic chemoradiotherapy with positive outcomes. In vitro investigation revealed that these nanoplatforms bear excellent biosafety, great tumor cell killing ability and radiosensitizing capacity. In addition, high cancer-suppression efficiency was observed through in vivo studies. It is worth mentioning that co-use of CuFe2O4@BSA-FA-CUR nanoplatforms and X-ray radiation led to complete tumor ablation in almost all of the treated mice. No mortality or radiation-induced normal tissue toxicity were observed following administration of CuFe2O4@BSA-FA-CUR nanoparticles which highlights the biosafety of these submicron scale entities. These results offer powerful evidence for the potential capability of CuFe2O4@BSA-FA-CUR in radiosensitization of malignant tumors and opens up a new avenue of research in this area.


Assuntos
Antineoplásicos , Curcumina , Nanopartículas , Neoplasias , Camundongos , Animais , Antineoplásicos/uso terapêutico , Portadores de Fármacos , Neoplasias/tratamento farmacológico , Quimiorradioterapia
10.
Biomater Adv ; 140: 213090, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36027669

RESUMO

Janus heterostructures based on bimetallic nanoparticles have emerged as effective radiosensitizers owing to their radiosensitization capabilities in cancer cells. In this context, this study aims at developing a novel bimetallic nanoradiosensitizer, Bi2S3-Fe3O4, to enhance tumor accumulation and promote radiation-induced DNA damage while reducing adverse effects. Due to the presence of both iron oxide and bismuth sulfide metallic nanoparticles in these newly developed nanoparticle, strong radiosensitizing capacity is anticipated through the generation of reactive oxygen species (ROS) to induce DNA damage under X-Ray irradiation. To improve blood circulation time, biocompatibility, colloidal stability, and tuning surface functionalization, the surface of Bi2S3-Fe3O4 bimetallic nanoparticles was coated with bovine serum albumin (BSA). Moreover, to achieve higher cellular uptake and efficient tumor site specificity, folic acid (FA) as a targeting moiety was conjugated onto the bimetallic nanoparticles, termed Bi2S3@BSA-Fe3O4-FA. Biocompatibility, safety, radiation-induced DNA damage by ROS activation and generation, and radiosensitizing ability were confirmed via in vitro and in vivo assays. The administration of Bi2S3@BSA-Fe3O4-FA in 4T1 breast cancer murine model upon X-ray radiation revealed highly effective tumor eradication without causing any mortality or severe toxicity in healthy tissues. These findings offer compelling evidence for the potential capability of Bi2S3@BSA-Fe3O4-FA as an ideal nanoparticle for radiation-induced cancer therapy and open interesting avenues of future research in this area.


Assuntos
Neoplasias da Mama , Nanopartículas Metálicas , Radiossensibilizantes , Animais , Bismuto , Neoplasias da Mama/tratamento farmacológico , Feminino , Óxido Ferroso-Férrico , Humanos , Nanopartículas Metálicas/uso terapêutico , Camundongos , Radiossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio , Soroalbumina Bovina/química , Sulfetos
11.
Mol Biotechnol ; 64(12): 1376-1387, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35670994

RESUMO

The discovery of bacterial-derived Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has revolutionized genome engineering and gene therapy due to its wide range of applications. One of the major challenging issues in CRISPR/Cas system is the lack of an efficient, safe, and clinically suitable delivery of the system's components into target cells. Here, we describe the development of polyethylenimine coated-bovine serum albumin nanoparticles (BSA-PEI NPs) for efficient delivery of CRISPR/Cas9 system in both DNA (px458 plasmid) and ribonucleoprotein (RNP) forms into MDA-MB-231 human breast cancer cell line. Our data showed that synthesized BSA-PEI (BP) NPs delivered plasmid px458 at concentrations of 0.15, 0.25, and 0.35 µg/µl with efficiencies of approximately 29.7, 54.8, and 84.1% into MDA-MB-231 cells, respectively. Our study demonstrated that Cas9/sgRNA RNP complex efficiently (~ 92.6%) delivered by BSA-PEI NPs into the same cells. Analysis of toxicity and biocompatibility of synthesized NPs on human red blood cells, MDA-MB-231 cells, and mice showed that the selected concentration (28 µg/µl) of BSA-PEI NPs for transfection had no remarkable toxicity effects. Thus, obtained results suggest BSA-PEI NPs as one of the most promising carrier for delivering CRISPR/Cas9 to target cells.


Assuntos
Sistemas CRISPR-Cas , Nanopartículas , Animais , Proteína 9 Associada à CRISPR/genética , Humanos , Camundongos , Polietilenoimina , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Soroalbumina Bovina
12.
Nanomedicine (Lond) ; 17(4): 201-217, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35037483

RESUMO

Aim: The aim of the present investigation was to develop niosomes containing both curcumin (CUR) and methotrexate (MTX). Also, the combinational effect of CUR and MTX in both free and niosomal forms on growth inhibition potential and induction of apoptosis in the HCT-116 cell line were exploited. Materials & methods: Niosomes were prepared by the thin-film hydration method and their physicochemical properties were determined by various techniques. Cellular uptake, cell apoptosis, wound healing and MTT assay were conducted to ascertain niosomes' feasibility for cancer therapy. Results: The combination of CUR and MTX in niosomal formulation showed more toxicity than their combination in free form. Conclusion: The nanocarrier-based approach was effective for the codelivery of CUR and MTX against cancer cells in vitro.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Curcumina , Antineoplásicos/química , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Curcumina/química , Células HCT116 , Humanos , Lipossomos/química , Metotrexato/química , Tamanho da Partícula
13.
Int J Biol Macromol ; 200: 335-349, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34999039

RESUMO

Insulin-like growth factor-1 receptor (IGF-1R) is expressed in malignant and normal breast tissue, and its intermittent activation by multiple IGF-1 signaling pathways leads to neoplasm cell proliferation, impaired apoptosis, increased survival, and resistance to cytotoxic therapeutic agents. Therefore, simultaneous suppression of the receptor and its cognate ligand would be a powerful promising strategy inhibiting malignant phenotypes of breast cancer cells. In the present study, Methoxypoly(ethylene glycol) - Poly(caprolactone) was hybridized with Dimethyldioctadecylammonium bromide (DDAB) cationic lipid (mPEG-PCL-DDAB) nanoparticles (NPs) and used as a carrier for simultaneous delivery of lycopene and insulin-like growth factor 1 receptor-specific lycopene encapsulated-mPEG-PCL-DDAB nanoparticle/siRNA to MCF-7 breast cancer cells. Then, the antitumor effects of this construct were evaluated in vitro. The results demonstrated that the synthesized mPEG-PCL-DDAB nanoparticle had suitable physicochemical properties. The use of mPEG-PCL-DDAB nanoparticle-loaded anti-insulin-like growth factor 1 receptor-siRNA and lycopene dramatically induced the process of apoptosis and arrested cell cycle in the MCF-7 tumor cell lines. In general, the findings of this study demonstrated the potency of mPEG-PCL-DDAB nanoparticles for dual delivery of siRNA, and lycopene in breast cancer cell lines followed the induction of apoptosis.


Assuntos
Lipossomos , Nanopartículas
14.
Nanomedicine (Lond) ; 17(2): 95-105, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35000461

RESUMO

Aim: To prepare a novel hybrid system for the controlled release and delivery of curcumin (CUR). Methods: A method for the ultrasound-assisted fabrication of protein-modified nanosized graphene oxide-like carbon-based nanoparticles (CBNPs) was developed. After being modified with bovine serum albumin (BSA), CUR was loaded onto the synthesized hybrid (labeled CBNPs@BSA-CUR). The structure and properties of the synthesized nanoparticles were elucidated using transmission electron microscopy (TEM), atomic force microscopy (AFM), ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR) and x-ray photoelectron spectroscopy (XPS) methods. Results: CBNPs@BSA-CUR showed pH sensitivity and were calculated as controlled CUR release behavior. The drug-free system exhibited good biocompatibility and was nontoxic. However, CBNPs@BSA-CUR showed acceptable antiproliferative ability against MCF-7 breast cancer cells. Conclusion: CBNPs@BSA-CUR could be considered a highly promising nontoxic nanocarrier for the delivery of CUR with good biosafety.


Assuntos
Curcumina , Nanopartículas , Curcumina/química , Curcumina/farmacologia , Portadores de Fármacos/química , Humanos , Células MCF-7 , Nanopartículas/química , Soroalbumina Bovina/química
15.
Bioact Mater ; 7: 74-84, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34466718

RESUMO

Synchronous chemotherapy and radiotherapy, termed chemoradiation therapy, is now an important standard regime for synergistic cancer treatment. For such treatment, nanoparticles can serve as improved carriers of chemotherapeutics into tumors and as better radiosensitizers for localized radiotherapy. Herein, we designed a Schottky-type theranostic heterostructure, Bi2S3-Au, with deep level defects (DLDs) in Bi2S3 as a nano-radiosensitizer and CT imaging contrast agent which can generate reactive free radicals to initiate DNA damage within tumor cells under X-ray irradiation. Methotrexate (MTX) was conjugated onto the Bi2S3-Au nanoparticles as a chemotherapeutic agent showing enzymatic stimuli-responsive release behavior. The designed hybrid system also contained curcumin (CUR), which cannot only serve as a nutritional supplement for chemotherapy, but also can play an important role in the radioprotection of normal cells. Impressively, this combined one-dose chemoradiation therapeutic injection of co-drug loaded bimetallic multifunctional theranostic nanoparticles with a one-time clinical X-ray irradiation, completely eradicated tumors in mice after approximately 20 days after irradiation showing extremely effective anticancer efficacy which should be further studied for numerous anti-cancer applications.

16.
Pharm Dev Technol ; 27(1): 19-24, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34895033

RESUMO

In this project, a biocompatible block copolymer including poly ethylene glycol and poly caprolactone was synthesized using ring-opening reaction. Then, the copolymer was conjugated to folic acid using lysine as a linker. Also, curcumin (CUR) was used as a therapeutic anticancer agent. Nanoprecipitation method was used to prepare CUR-loaded polymeric micelles. Different methods including Fourier-transform infrared spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS) were used to characterize the prepared nanocarriers (NCs). MTT assay and hemolysis assay were used to evaluate in vitro anticancer efficiency and biocompatibility of the prepared NCs, respectively. The results proved efficiency of NCs as a drug delivery system (DDS) in various aspects such as physicochemical properties and biocompatibility. Also, in vivo results showed that NCs did not show any severe weight loss and side effects on mice, and the anti-cancer study results of the CUR-loaded NCs proved that the conjugation of folic acid on the surface of NCs as a targeting agent could increase the therapeutic efficacy of CUR.


Assuntos
Curcumina , Neoplasias , Animais , Curcumina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Ácido Fólico/química , Camundongos , Micelas , Neoplasias/tratamento farmacológico , Polietilenoglicóis/química , Polímeros/química
17.
Adv Healthc Mater ; 11(3): e2102321, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34800003

RESUMO

An optimal radiosensitizer with improved tumor retention has an important effect on tumor radiation therapy. Herein, gold nanoparticles (Au NPs) and drug-containing, mPEG-conjugated CUR (mPEG-CUR), self-assembled NPs (mPEG-CUR@Au) are developed and evaluated as a drug carrier and radiosensitizer in a breast cancer mice model. As a result, cancer therapy efficacy is improved significantly by applying all-in-one NPs to achieve synchronous chemoradiotherapy, as evidenced by studies evaluating cell viability, proliferation, and ROS production. In vivo anticancer experiments show that the mPEG-CUR@Au system improves the radiation sensitivity of 4T1 mammary carcinoma and completely abrogates breast cancer.


Assuntos
Curcumina , Nanopartículas Metálicas , Nanopartículas , Neoplasias , Pró-Fármacos , Animais , Linhagem Celular Tumoral , Curcumina/uso terapêutico , Ouro , Nanopartículas Metálicas/uso terapêutico , Camundongos , Nanoconjugados , Neoplasias/tratamento farmacológico , Pró-Fármacos/farmacologia , Raios X
18.
J Mater Chem B ; 9(22): 4510-4522, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34027529

RESUMO

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research. The present study aims to design a nanoplatform that offers the opportunity to enhance antitumor activity while minimizing side effects. Given the Au-mediated X-ray radiation enhancement and the ability of Fe-based nanomaterials to create reactive oxygen species (ROS) and DNA damage, we anticipated that bimetallic Fe3O4-Au heterodimer would bring strong radiosensitizing capacity. Fe3O4-Au heterodimer surface was covered with bovine serum albumin (BSA) to achieve good surface functionality, stability and prolonged blood circulation. Folic acid (FA) moieties were added to the nanoformulation to increase tumor-homing, specificity and uptake. Finally, curcumin (CUR) was incorporated into the nanoparticle to function as a natural anticancer agent. The integration of all these components has yielded a single nanoplatform, Fe3O4-Au-BSA-FA-CUR, capable of successfully fulfilling the mission of superadditive cancer therapy to avoid the risks of organ removal surgery. The efficacy of the proposed nanoplatform was investigated in vitro and in vivo. High radiosensitizing ability, X-ray-induced ROS generation and DNA damage, and good biocompatibility were demonstrated through in vitro experiments. Also, the administration of Fe3O4-Au-BSA-FA-CUR with X-ray irradiation completely eradicated the tumor without any mortality and toxicity in healthy tissues in vivo. Our results highlight the potential of CUR-loaded Fe3O4-Au-BSA-FA heteronanostructure to enable synergistic localized radiochemotherapy and open up a new door to attractive possibilities that warrant further exploration.


Assuntos
Neoplasias da Mama/terapia , Compostos Férricos/farmacologia , Ouro/farmacologia , Radiossensibilizantes/farmacologia , Animais , Linhagem Celular Tumoral , Quimiorradioterapia , Camundongos
19.
Nanomedicine (Lond) ; 16(6): 497-516, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33683164

RESUMO

COVID-19, as an emerging infectious disease, has caused significant mortality and morbidity along with socioeconomic impact. No effective treatment or vaccine has been approved yet for this pandemic disease. Cutting-edge tools, especially nanotechnology, should be strongly considered to tackle this virus. This review aims to propose several strategies to design and fabricate effective diagnostic and therapeutic agents against COVID-19 by the aid of nanotechnology. Polymeric, inorganic self-assembling materials and peptide-based nanoparticles are promising tools for battling COVID-19 as well as its rapid diagnosis. This review summarizes all of the exciting advances nanomaterials are making toward COVID-19 prevention, diagnosis and therapy.


Assuntos
COVID-19/diagnóstico , COVID-19/terapia , Nanomedicina/métodos , Nanoestruturas/uso terapêutico , Animais , COVID-19/prevenção & controle , Teste para COVID-19/métodos , Humanos , Nanoestruturas/química , Nanotecnologia/métodos , Peptídeos/química , Peptídeos/uso terapêutico , Polímeros/química , Polímeros/uso terapêutico , Proteínas/química , Proteínas/uso terapêutico , SARS-CoV-2/isolamento & purificação
20.
Iran Biomed J ; 25(2): 106-16, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33465843

RESUMO

Background: To study the anticancer activity of Plantago major, we assessed the effect of ethanolic, methanolic and acetonic extracts of this plant on HCT-116, SW-480, and HEK-293 cell lines as control. Methods: The cytotoxic activity, biocompatibility, and toxicity were evaluated by MTT assay, hemolysis, and Artemia salina-LD50 (on mice) tests, respectively. The analysis of the extracts was performed by GC-MS analysis. Results: The results showed that all the extracts had the most antiproliferative properties on the HCT-116 cell line. The P. major root extract was more effective than the aerial parts, and IC50 values for ethanolic, methanolic and acetonic root extracts were 405.59, 470.16, and 82.26 µg/mL, respectively on HCT-116 cell line at 72 h. Hemolysis degree of the ethanolic extract of aerial and root parts were approximately 1% at 400 µg/mL.. Using the ethanolic extracts, the Artemia survived every concentration, and no toxicity was observed. One week after the oral administration of different parts of P. major extracts, none of the mice died, even those were administered 2000 mg/kg. The results of GC/MS analysis showed that P. major extracts contain potential anticancer compounds, such as stearic acid (8.61%) in aerial parts of methanolic extract and 1,2- Benzenedicarboxylic acid, mono(2-ethylhexyl)ester (88.07% and 40.63%) in aerial and root parts of acetonic extract of P. major. Conclusion: Our findings suggest that the P. major is a source of potential compounds with antiproliferative properties.


Assuntos
Materiais Biocompatíveis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantago/química , Plantas Medicinais/química , Administração Oral , Animais , Artemia , Peso Corporal/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Etanol , Cromatografia Gasosa-Espectrometria de Massas , Células HEK293 , Hemólise/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Camundongos , Extratos Vegetais/toxicidade , Testes de Toxicidade Aguda
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