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1.
MAGMA ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38795276

RESUMO

OBJECTIVE: Glioblastoma multiforme is a highly aggressive form of brain cancer, and early diagnosis plays a pivotal role in improving patient survival rates. In this regard, molecular magnetic resonance imaging has emerged as a promising imaging modality due to its exceptional sensitivity to minute tissue changes and the ability to penetrate deep into the brain. This study aimed to assess the efficacy of a novel contrast agent in detecting gliomas during MRI scans. MATERIALS AND METHODS: The contrast agent utilized modified chitosan coating on manganese oxide nanoparticles. The modification included adding methotrexate and 5-aminolevulinic acid (MnO2/CS@5-ALA-MTX) to target cells with overexpressed folate receptors and breaking down excess hydrogen peroxide in tumor tissue, resulting in enhanced signal intensity in T1-weighted MR images but diminished signal intensity in T2*-weighted MR images. RESULTS: The nanosystem was characterized and evaluated in MR imaging, safety, and ability to target cells both in vivo and in vitro. MTX-free nanoparticles (MnO2/CS@5-ALA NPs) had no obvious cytotoxicity on cell lines U87MG and NIH3T3 after 24/48 h at a concentration of up to 160 µgr/mL (cell viability more than 80%). In this system, methotrexate enables tumor targeting and the MnO2/5-ALA improves T1-T2*-weighted MRI. In addition, MRI scans of mice with M109 carcinoma indicated significant tumor uptake and NP capacity to improve the positive contrast effect. CONCLUSION: This developed MnO2/CS@5-ALA-MTX nanoparticle system may exhibit great potential in the accurate diagnosis of folate receptor over-expressing cancers such as glioblastoma.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38839606

RESUMO

This study aims to estimate organ dose and cancer risks, establish region-specific diagnostic reference levels (DRLs), and determine achievable doses (ADs) for common CT procedures in adults in the northwest of Iran. Effective and organ doses were estimated using VirtualDoseCT software in a sample of 480 adult patients who underwent head, sinus, chest, and abdomen-pelvis (AP) CT scans. The guidelines provided by the BEIR VII report were utilized to estimate cancer risks. Effective and organ doses for specific procedures were determined, with the highest mean organ dose being observed in the brain during head CT examinations, with a value of 54.02 mGy. It was observed that the lungs in chest examinations and the colon in AP examinations had the highest risk of cancer, with rates of 30.72 and 21.37 per 100,000 persons, respectively. Higher cancer risk values were generally exhibited by females compared to males. The DRLs for common CT examinations were established as follows: Head CT (CTDIvol 41 mGy, DLP 760 mGy cm), Sinus CT (CTDIvol 16 mGy, DLP 261 mGy cm), Chest CT (CTDIvol 8 mGy, DLP 287 mGy cm), and AP CT (CTDIvol 9 mGy, DLP 508 mGy cm). Significant variations in dose distribution among facilities were identified, indicating the need for optimization. The study highlights the importance of minimizing radiation exposure to critical organs and promoting patient safety in CT examinations. The establishment of region-specific DRLs and ADs can help optimize radiation doses and reduce cancer risks for patients.

3.
Environ Res ; 236(Pt 1): 116526, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37487920

RESUMO

Photothermal therapy (PTT) is an emerging non-invasive method used in cancer treatment. In PTT, near-infrared laser light is absorbed by a chromophore and converted into heat within the tumor tissue. PTT for cancer usually combines a variety of interactive plasmonic nanomaterials with laser irradiation. PTT enjoys PT agents with high conversion efficiency to convert light into heat to destroy malignant tissue. In this review, published studies concerned with the use of nanoparticles (NPs) in PTT were collected by a systematic and comprehensive search of PubMed, Cochrane, Embase, and Scopus databases. Gold, silver and iron NPs were the most frequent choice in PTT. The use of surface modified NPs allowed selective delivery and led to a precise controlled increase in the local temperature. The presence of NPs during PTT can increase the reactive generation of oxygen species, damage the DNA and mitochondria, leading to cancer cell death mainly via apoptosis. Many studies recently used core-shell metal NPs, and the effects of the polymer coating or ligands targeted to specific cellular receptors in order to increase PTT efficiency were often reported. The effective parameters (NP type, size, concentration, coated polymers or attached ligands, exposure conditions, cell line or type, and cell death mechanisms) were investigated individually. With the advances in chemical synthesis technology, NPs with different shapes, sizes, and coatings can be prepared with desirable properties, to achieve multimodal cancer treatment with precision and specificity.

4.
MAGMA ; 36(5): 779-795, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37074514

RESUMO

OBJECTIVE: A novel efficient pH-sensitive targeted magnetic resonance imaging (MRI) contrast agent and innovative radio-sensitizing system were synthesized based on MnO2 NPs coated with biocompatible poly-dimethyl-amino-ethyl methacrylate-Co-itaconic acid, (DMAEMA-Co-IA) and targeted with methotrexate (MTX). MATERIALS AND METHODS: The as-established NPs were fully characterized and evaluated for MRI signal enhancement, relaxivity, in vitro cell targeting, cell toxicity, blood compatibility, and radiotherapy (RT) efficacy. RESULTS: The targeted NPs MnO2@Poly(DMAEMA-Co-IA) and MTX-loaded NPs inhibited MCF-7 cell viability more effectively than free MTX after 24 and 48 h, respectively, with no noticeable toxicity. Additionally, the insignificant hemolytic activity demonstrated their proper hemo-compatibility. T1-weighted magnetic resonance imaging was used to distinguish the differential uptake of the produced MnO2@Poly(DMAEMA-Co-IA)-MTX NPs in malignant cells compared to normal ones in the presence of high and low MTX receptor cells (MCF-7 and MCF-10A, respectively). In MRI, the produced theranostic NPs displayed pH-responsive contrast enhancement. As shown by in vitro assays, treatment of cells with MnO2@Poly(DMAEMA-Co-IA)-MTX NPs prior to radiotherapy in hypoxic conditions significantly enhanced therapeutic efficacy. CONCLUSION: We draw the conclusion that using MnO2@Poly(DMAEMA-Co-IA)-MTX NPs in MR imaging and combination radiotherapy may be a successful method for imaging and radiation therapy of hypoxia cells.


Assuntos
Neoplasias da Mama , Nanopartículas , Humanos , Feminino , Metotrexato/farmacologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Compostos de Manganês , Óxidos , Metacrilatos , Meios de Contraste/farmacologia , Imageamento por Ressonância Magnética , Linhagem Celular Tumoral
5.
Cancer Cell Int ; 21(1): 391, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289841

RESUMO

Glioblastoma, WHO grade IV astrocytoma, is the most aggressive type of brain tumors. These cancerous cells have a rapid growth rate, tendency to penetrate vital brain structures, molecular heterogeneity, etc. and this cancer is associated with a poor prognosis and low survival rate. Due to the resistance of glioblastoma cells to conventional therapeutic modalities (such as radiation therapy and chemotherapy) as well as the adverse effects of these modalities, the researchers have attempted to discover an appropriate alternative or adjuvant treatment for glioblastoma. Resveratrol, as an herbal and natural polyphenolic compound, has anti-tumoral property and has shown to be effective in GBM treatment. Resveratrol exerts its anti-tumoral effect through various mechanisms such as regulation of cell cycle progression and cell proliferation, autophagy, oxidant system, apoptosis pathways, and so on. Resveratrol in combination with radiation therapy and chemotherapy has also been used. In the present study, we summarized the current findings on therapeutic potentials of resveratrol in glioblastoma radiotherapy and chemotherapy.

6.
Bioorg Med Chem ; 30: 115944, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33352388

RESUMO

In an attempt to find new potent cytotoxic compounds, several mono- and bis-pyrazolophthalazines 4a-m and 6a-h were synthesized through an efficient, one-pot, three- and pseudo five-component synthetic approach. All derivatives were evaluated for their in vitro cytotoxic activities against four human cancer cell lines of A549, HepG2, MCF-7, and HT29. Compound 4e showed low toxicity against normal cell lines (MRC-5 and MCF 10A, IC50 > 200 µM) and excellent cytotoxic activity against A549 cell line with IC50 value of 1.25 ± 0.19 µM, which was 1.8 times more potent than doxorubicin (IC50 = 2.31 ± 0.13 µM). In addition, compound 6c exhibited remarkable cytotoxic activity against A549 and MCF-7 cell lines (IC50 = 1.35 ± 0.12 and 0.49 ± 0.01 µM, respectively), more than two-fold higher than that of doxorubicin. The binding properties of the best active mono- and bis-pyrazolophthalazine (4e and 6c) with HSA and DNA were fully evaluated by various techniques including UV-Vis absorption, circular dichroism (CD), Zeta potential and dynamic light scattering analyses indicating interaction of the compounds with the secondary structure of HSA and significant change of DNA conformation, presumably via a groove binding mechanism. Additionally, molecular docking and site-selective binding studies confirmed the fundamental interaction of compounds 4e and 6c with base pairs of DNA. Compounds 4e and 6c showed promising features to be considered as potential lead structures for further studies in cancer therapy.


Assuntos
Antineoplásicos/farmacologia , DNA/química , Desenho de Fármacos , Simulação de Acoplamento Molecular , Ftalazinas/farmacologia , Albumina Sérica Humana/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Sítios de Ligação/efeitos dos fármacos , Bovinos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Ftalazinas/síntese química , Ftalazinas/química , Relação Estrutura-Atividade
7.
MAGMA ; 32(4): 487-500, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30730021

RESUMO

OBJECTIVES: In this study, a novel targeted MRI contrast agent was developed by coating gadolinium oxide nanoparticles (Gd2O3 NPs) with ß-cyclodextrin (CD)-based polyester and targeted by folic acid (FA). MATERIALS AND METHODS: The developed Gd2O3@PCD-FA MRI contrast agent was characterized and evaluated in relaxivity, in vitro cell targeting, cell toxicity, blood compatibility and in vivo tumor MR contrast enhancement. RESULTS: In vitro cytotoxicity and hemolysis assays revealed that Gd2O3@PCD-FA NPs have no significant cytotoxicity after 24 and 48 h against normal human breast cell line (MCF-10A) at concentration of up to 50 µg Gd+3/mL and have high blood compatibility at concentration of up to 500 µg Gd+3/mL. In vitro MR imaging experiments showed that Gd2O3@PCD-FA NPs enable targeted contrast T1- and T2-weighted MR imaging of M109 as overexpressing folate receptor cells. Besides, the in vivo analysis indicated that the maximum contrast-to-noise ratio (CNR) of tumor in mice increased after injection of Gd2O3@PCD-FA up to 5.89 ± 1.3 within 1 h under T1-weighted imaging mode and reduced to 1.45 ± 0.44 after 12 h. While CNR increased up to maximum value of 1.98 ± 0.28 after injection of Gd2O3@PCD within 6 h and reduced to 1.12 ± 0.13 within 12 h. CONCLUSION: The results indicate the potential of Gd2O3@PCD-FA to serve as a novel targeted nano-contrast agent in MRI.


Assuntos
Meios de Contraste/farmacologia , Ciclodextrinas/química , Ácido Fólico/química , Gadolínio/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Ácido Pentético/química , Animais , Linhagem Celular Tumoral , Materiais Revestidos Biocompatíveis , Relação Dose-Resposta a Droga , Hemólise , Humanos , Imageamento por Ressonância Magnética , Camundongos , Transplante de Neoplasias , Termogravimetria
8.
Contemp Oncol (Pozn) ; 23(1): 7-15, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061631

RESUMO

In Iran, a developing country in southwest Asia, an epidemiologic transition is underway from communicable to noncommunicable diseases. In Iran, cancer is the second largest group of chronic non-communicable diseases (NCDs) and the third most common cause of death following heart disease, accidents and other natural phenomena. There are some studies reporting an increasing trend in the incidence and mortality rate of a variety of cancers in Iran. Therefore, controlling and preventive interventions pertaining to cancers must be a main priority for health policy and it is recommended that the high-risk population receive earlier screening. In this review, incidence and mortality of colorectal, lung, liver, thyroid, and bladder cancers in Iran are reported.

9.
Contemp Oncol (Pozn) ; 21(3): 232-239, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29180932

RESUMO

AIM OF THE STUDY: Our objective was to quantify the accuracy of dose calculation in the build-up region of the tangential field of the breast for a TiGRT treatment planning system (TPS). MATERIAL AND METHODS: Thermoluminescent dosimeter (TLD) chips were arranged in a RANDO phantom for the dose measurement. TiGRT TPS was also used for the dose calculation. Finally, confidence limit values were obtained to quantify the accuracy of the dose calculation of the TPS at the build-up region. RESULTS: In the open field, for gantry angles of 15°, 30°, and 60°, the confidence limit values were 17.68, 19.97, and 34.62 at a depth of 5 mm, and 24.01, 19.07, and 15.74 at a depth of 15 mm, respectively. In the wedge field, for gantry angles of 15°, 30°, and 60°, the confidence limit values were 21.64, 26.80, and 34.87 at a depth of 5 mm, and 27.92, 22.04, and 20.03 at a depth of 15 mm, respectively. Additionally, the findings showed that at a depth of 5 mm, the confidence limit values increased with increasing gantry angle while at a depth of 15 mm, the confidence limit values decreased with increasing gantry angle. CONCLUSIONS: Overall, TiGRT TPS overestimated doses compared to TLD measurements, and the confidence limit values were greater for the wedge field than for the open fields. Our findings suggest that the assessment of dose distributions in large-dose gradient regions (i.e. build-up region) should not entirely rely on TPS calculations.

10.
Int J Pharm ; 659: 124264, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38788969

RESUMO

Nanotechnology-based diagnostic, and therapeutic approaches revolutionized the field of cancer detection, and treatment, offering tremendous potential for cost-effective interventions in the early stages of disease. This research synthesized bismuth oxide (Bi2O3) nanoparticles (NPs) that were modified with polycyclodextrin (PCD), and functionalized with glucose (Glu) to load curcumin (CUR) for CT imaging and chemo-radiotherapy applications in Breast Cancer. The prepared Bi2O3@PCD-CUR-Glu NPs underwent comprehensive characterization, encompassing various aspects, including cell migration, cytotoxicity, cellular uptake, blood compatibility, reactive oxygen species (ROS) generation ability, real-time PCR analysis, in-vivo safety assessment, in-vivo anti-tumor efficacy, as well as in-vitro CT contrast and X-ray RT enhancement evaluation. CT scan was conducted before and after (1 and 3 h) intravenous injection of Bi2O3@PCD-CUR-Glu NPs. Through the use of coupled plasma optical emission spectrometry (ICP-OES) analysis, the final prepared nanoparticle distribution in the Bab/c mice was assessed. The spherical NPs that were ultimately synthesized and had a diameter of around 80 nm demonstrated exceptional toxicity towards the SKBr-3 breast cancer cell line. The cell viability was at its lowest level after 48 h of exposure to a radiation dose of 2 Gy at a concentration of 100 µg/mL. The combined treatment involving using Bi2O3@PCD-CUR-Glu NPs along with X-ray radiation showed a substantial increase in the generation of ROS, specifically a remarkable 420 % growth. Gene expression analysis indicated that the expression levels of P53, and BAX pro-apoptotic genes were significantly increased. The in-vitro CT imaging analysis conducted unequivocally demonstrated the notable superiority of NPs over Omnipaque in terms of X-ray absorption capacity, a staggering 1.52-fold increase at 80 kVp. The resultsdemonstrated that the targeted Bi2O3@PCD-CUR-Glu NPs could enhance the visibility of a small mice tumor that is detectable by computed tomography and made visible through X-ray attenuation. Results suggested that Bi2O3@PCD-CUR-Glu NPs, integrated with CT imaging and chemo-radiotherapy, have great potential as a versatile theranostic system for clinical application.


Assuntos
Bismuto , Neoplasias da Mama , Curcumina , Camundongos Endogâmicos BALB C , Nanopartículas , Tomografia Computadorizada por Raios X , beta-Ciclodextrinas , Curcumina/administração & dosagem , Curcumina/química , Curcumina/farmacologia , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Humanos , Linhagem Celular Tumoral , Tomografia Computadorizada por Raios X/métodos , beta-Ciclodextrinas/química , Bismuto/química , Bismuto/administração & dosagem , Nanopartículas/química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Quimiorradioterapia/métodos , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/química
11.
Sci Rep ; 13(1): 14606, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37670132

RESUMO

This study introduces a simple method for preparing a new generation of MnO2 nanomaterials (MNMs) using tannic acid as a template. Two shapes of MnO2 NMs, flower-like M1-MnO2 and near-spherical M2-MnO2, were prepared and compared as dual-active nanozymes and contrast agents in magnetic resonance imaging (MRI). Various parameters, including the crystallinity, morphology, magnetic saturation (Ms), surface functionality, surface area, and porosity of the MNMs were investigated. Flower-like M1-MnO2 NMs were biocompatible and exhibited pH-sensitive oxidase and peroxidase mimetic activity, more potent than near-spherical M2-MnO2. Furthermore, the signal intensity and r1 relaxivity strongly depended on the crystallinity, morphology, pore size, and specific surface area of the synthesized MNMs. Our findings suggest that flower-like M1-MnO2 NM with acceptable dual-enzyme mimetic (oxidase-like and peroxidase-like) and T1 MRI contrast activities could be employed as a promising theranostic system for future purposes.


Assuntos
Meios de Contraste , Nanoestruturas , Compostos de Manganês , Óxidos , Peroxidase , Imageamento por Ressonância Magnética , Peroxidases
12.
J Med Signals Sens ; 12(1): 64-68, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265467

RESUMO

Background: Nowadays, there has been a growing demand for low-dose computed tomography (LDCT) protocols. CT has a critical role in the management of the diagnosis chain of pulmonary disease, especially in lung cancer screening. There have been introduced several dose reduction methods, however, most of them are time-consuming, intricate, and vendor-based strategies that are hardly used in clinics routinely. This study aims to evaluate the image quality and pulmonary nodule detectability of LDCT protocols that are feasible and easy implemented. Image quality was analyzed in a general quality control phantom (Gammex) and then in a manmade lung phantom with nodules-equivalent objects. Methods: This study was designed in a two steps, in the first step, a feasible low-dose lung CT protocol was selected with quality assessment of accreditation phantom image. In the second step, the selected low-dose protocol with an appropriate image quality was performed on a manmade lung phantom in which there were objects equivalent to the pulmonary nodule. Finally, image quality parameters of the phantom at the appropriate scan protocol were compared with the standard protocol. Results: A reduction of about 17% of kVp and 46% in tube current leads to dose reduction by about 70%. The contrast-to-noise ratio in the low-dose protocol remained almost unchanged. The signal-to-noise ratio in the low-dose protocol decreased by approximately 32%, and the noise level has increased by about 1.5 times. However, this reduction method hardly affected the detectability of nodules in man-made pulmonary phantom. Conclusions: Here, we demonstrated that the LDCT scan has an insignificant effect on the perception of lung nodules. In this study, patient dose in lung CT was reduced by modifying of kVp and mAs about approximately 70%. Hence, to step in toward low-dose strategies in medical imaging clinics, using easy-implemented and feasible low-dose strategies may be helpful.

13.
Biofactors ; 48(3): 597-610, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35080781

RESUMO

Although the chemotherapeutic drug, doxorubicin, is commonly used to treat various malignant tumors, its clinical use is restricted because of its toxicity especially cardiotoxicity. The use of curcumin may alleviate some of the doxorubicin-induced cardiotoxic effects. Especially, using the nano-formulation of curcumin can overcome the poor bioavailability of curcumin and enhance its physicochemical properties regarding its efficacy. In this study, we systematically reviewed the potential cardioprotective effects of nano-curcumin against the doxorubicin-induced cardiotoxicity. A systematic search was accomplished based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for the identification of all relevant articles on "the role of nano-curcumin on doxorubicin-induced cardiotoxicity" in the electronic databases of Scopus, PubMed, and Web of Science up to July 2021. One hundred and sixty-nine articles were screened following a predefined set of inclusion and exclusion criteria. Ten eligible scientific papers were finally included in the present systematic review. The administration of doxorubicin reduced the body and heart weights of mice/rats compared to the control groups. In contrast, the combined treatment of doxorubicin and nano-curcumin increased the body and heart weights of animals compared with the doxorubicin-treated groups alone. Furthermore, doxorubicin could significantly induce the biochemical and histological changes in the cardiac tissue; however, coadministration of nano-curcumin formulation demonstrated a pattern opposite to the doxorubicin-induced changes. The coadministration of nano-curcumin alleviates the doxorubicin-induced cardiotoxicity through various mechanisms including antioxidant, anti-inflammatory, and antiapoptotic effects. Also, the cardioprotective effect of nano-curcumin formulation against doxorubicin-induced cardiotoxicity was higher than free curcumin.


Assuntos
Curcumina , Animais , Antioxidantes/farmacologia , Apoptose , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Curcumina/farmacologia , Curcumina/uso terapêutico , Doxorrubicina/toxicidade , Camundongos , Ratos
14.
Oral Radiol ; 37(1): 80-85, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32065334

RESUMO

OBJECTIVE: Although radiation exposure associated with dental radiography is relatively low, patient exposure must be kept practically low. Therefore, it is necessary for each country to establish its own diagnostic reference levels (DRLs) suitable for its equipment and practice. In the present study, dose-width product (DWP) values for panoramic dental radiography were measured and a local DRL was established. METHODS: Five panoramic devices from five radiology clinics of Kashan, Iran were selected to measure the DWP values of panoramic dental radiography. To investigate the DWP values, the parameters of each patient's exposure (e.g., tube voltage, tube current, and exposure time) at these five radiology clinics were extracted. Then, the dose value received by each patient was measured based on a CT pencil chamber. Finally, the overall median DWP values for the patients with small, medium, and large sizes were obtained, and these values were considered as the local DRLs for panoramic dental radiography. RESULTS: A total of 99 adult patients were included in the present study. The findings demonstrated that the median and third-quartile DWP values for these five radiology clinics ranged from 42.3 to 94.3 and 49.7 to 142.8 mGy mm, respectively. The local DRL values, which were established as the overall median DWP values, were 43.4, 52.0, and 80.3 mGy  mm for the adults with small, medium, and large sizes, respectively. CONCLUSION: The local DRL proposed in this study for the adult with standard/medium size was lower than those proposed by other reports and seemed acceptable for panoramic radiography in Kashan, Iran.


Assuntos
Níveis de Referência de Diagnóstico , Radiometria , Adulto , Humanos , Irã (Geográfico) , Doses de Radiação , Radiografia Panorâmica
15.
Carbohydr Polym ; 254: 117262, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357850

RESUMO

A novel theranostic nanoplatform was prepared based on Fe3O4 nanoparticles (NPs) coated with gadolinium ions decorated-polycyclodextrin (PCD) layer (Fe3O4@PCD-Gd) and employed for Curcumin (CUR) loading. The dissolution profile of CUR indicated a pH sensitive release manner. Fe3O4@PCD-Gd NPs exhibited no significant toxicity against both normal and cancerous cell lines (MCF 10A and 4T1, respectively); while the CUR-free NPs showed more toxicity against 4T1 than MCF 10A cells. In vivo anticancer study revealed appropriate capability of the system in tumor shrinking with no tissue toxicity and adverse effect on body weight. In vivo MR imaging of BALB/c mouse showed both T1 and T2 contrast enhancement on the tumor cells. Fe3O4@PCD-Gd/CUR NPs showed significant features as a promising multifunctional system having appropriate T1-T2 dual contrast enhancement and therapeutic efficacy in cancer theranostics.


Assuntos
Celulose , Ciclodextrinas , Gadolínio , Nanopartículas Magnéticas de Óxido de Ferro , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Nanomedicina Teranóstica/métodos , Animais , Antineoplásicos/administração & dosagem , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quelantes , Meios de Contraste , Curcumina/administração & dosagem , Sistemas de Liberação de Medicamentos , Hemólise/efeitos dos fármacos , Humanos , Técnicas In Vitro , Nanopartículas Magnéticas de Óxido de Ferro/química , Nanopartículas Magnéticas de Óxido de Ferro/toxicidade , Nanopartículas Magnéticas de Óxido de Ferro/ultraestrutura , Imageamento por Ressonância Magnética , Magnetismo , Masculino , Teste de Materiais , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Neoplasias Experimentais/patologia , Medicina de Precisão , Espectroscopia de Infravermelho com Transformada de Fourier
16.
J Drug Target ; 28(5): 533-546, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31842616

RESUMO

ß-Cyclodextrine-based polyester was coated on the surface of gadolinium oxide nanoparticles (NPs) and then functionalised with folic acid to produce an efficient pH-sensitive targeted theranostic system (Gd2O3@PCD-FA) for doxorubicin delivery and magnetic resonance imaging (MRI). Gd2O3@PCD-FA was fully characterised by FTIR, vibrating sample magnetometer, TGA, XRD, SEM and TEM analyses. The dissolution profile of DOX showed a pH sensitive release. No significant toxicity was observed for the targeted NPs (Gd2O3@PCD-FA) and DOX-loaded NPs inhibiting M109 cells viability more efficiently than free DOX. Moreover, the negligible hemolytic activity of the targeted NPs showed their appropriate hemocompatibility. The preferential uptake was observed for the developed Gd2O3@PCD-FA-DOX NPs in comparison with Dotarem using T1- and T2-weighted MRI in the presence of folate receptor-positive and folate receptor-negative cancer cells (M109 and 4T1, respectively). Furthermore, in vivo studies revealed that Gd2O3@PCD-FA-DOX not only exhibited considerably relaxivity performance as a contrast agent for MRI, but also improved in vivo anti-tumour efficacy of the system. The results suggest that Gd2O3@PCD-FA-DOX improves its therapeutic efficacy in the treatment of solid tumours and also reduces the adverse effects, so it could be proposed as a promising drug delivery system for chemotherapy and molecular imaging diagnosis in MRI.


Assuntos
Ciclodextrinas/química , Doxorrubicina/química , Gadolínio/química , Nanopartículas/química , Poliésteres/química , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Ciclodextrinas/farmacologia , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico/química , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Medicina de Precisão/métodos , Nanomedicina Teranóstica/métodos
17.
Carbohydr Polym ; 213: 70-78, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30879691

RESUMO

A novel ß-cyclodextrin-based nanosponge (CDNS) was proposed as curcumin (CUR) delivery system improving pharmacokinetics and anticancer activity of CUR. The effect of molar ratio of Epiclon (EPI) as cross-linker and ß-cyclodextrin (ßCD) on the porosity, surface area, swelling ratio, CUR solubility and loading capacity, rate of drug release and selective toxicity of the CDNSs was fully investigated. The high degree of cross-linking led to the formation of mesoporous CDNS having high specific surface area and high loading capacity. All CUR-free CDNSs showed no toxicity against MCF 10A and 4T1 cells as normal and cancerous cells, respectively. While CDNSs-CUR exhibited selective toxicity against cancerous cells. In sum, high CUR aqueous solubility, significant loading and controllable release of the CUR, outstanding and selective toxicity against cancerous cells make CDNS8-CUR (EPI/ßCD = 8) as promising candidate for further study in the cancer therapy.


Assuntos
Reagentes de Ligações Cruzadas/farmacologia , Curcumina/toxicidade , Nanopartículas/química , beta-Ciclodextrinas/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Reagentes de Ligações Cruzadas/administração & dosagem , Reagentes de Ligações Cruzadas/química , Curcumina/administração & dosagem , Curcumina/química , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Humanos , Camundongos , Estrutura Molecular , Tamanho da Partícula , Solubilidade , Relação Estrutura-Atividade , Propriedades de Superfície , Termodinâmica , beta-Ciclodextrinas/química
18.
J Cancer Res Ther ; 15(3): 517-521, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31169213

RESUMO

OBJECTIVE: Date palm seed extract (DPSE) has various compounds revealing antioxidant features. This study aimed to evaluate the radioprotective effect of DPSE in total body gamma irradiation. MATERIALS AND METHODS: At first, chemical characteristics of DPSE were analyzed by ultraviolet, visible and Fourier transform infrared spectroscopy. Then, the toxicity of DPSE was assessed. For this purpose, 60 mice were divided into five groups, and each of the groups were injected by the doses of 100, 200, 300, 400, and 500 mg/kg, respectively. At the termination of the experiment, mortality rate and weight loss of all mice were evaluated over a period of 30 days. Finally, the radioprotective effect of DPSE was evaluated by dividing 36 mice into three groups: control, test, and placebo and then were irradiated by Cobalt-60. RESULTS: According to the findings, there was no mortality due to DPSE. Furthermore, for the maximum dose of 500 mg/kg, the number of mice surviving at the termination of the experiment with and without injection of DPSE was reported as 83% and 41%, respectively. In addition, a significant difference was obtained between radiated mice with and without DPSE injection (P = 0.035). CONCLUSION: The findings showed that DPSE injected into mice before irradiation has no toxicity and could protect mice from lethal effects of total body irradiation. The use of DPSE as a new radioprotector agent in the human needs further studies, particularly clinical trials.


Assuntos
Raios gama , Phoeniceae/química , Extratos Vegetais/farmacologia , Protetores contra Radiação/farmacologia , Sementes/química , Animais , Raios gama/efeitos adversos , Masculino , Camundongos , Extratos Vegetais/química , Protetores contra Radiação/química , Análise Espectral , Taxa de Sobrevida , Irradiação Corporal Total
19.
J Colloid Interface Sci ; 556: 128-139, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31437658

RESUMO

Magnetic drug delivery system is one of the most important strategies for cancer diagnosis and treatment. In this study, a novel theranostic system was fabricated based on cyclodextrin nanosponge (CDNS) polymer anchored on the surface of Magnetite nanoparticles (Fe3O4/CDNS NPs) which was then decorated with folic acid (FA) as a targeting agent (Fe3O4/CDNS-FA). Curcumin (CUR), a hydrophobic model drug, was next loaded into the cyclodextrin cavity and polymeric matrix of CDNS (Fe3O4/CDNS-FA@CUR). The system was fully characterized. The in vitro release study revealed pH-sensitive behavior. Cytotoxicity assays indicated a negligible toxicity for CUR free Fe3O4/CDNS-FA NPs against both of M109 cancerous cells and MCF 10A normal cells. CUR-loaded Fe3O4/CDNS-FA NPs exhibited higher toxicity against M109 cancerous cells than MCF 10A normal cells (p < 0.05). Fe3O4/CDNS-FA@CUR NPs resulted in much more cell viability on normal cells than pure CUR (p < 0.05). Moreover, blood compatibility study showed minor hemolytic activity. In vitro MRI studies illustrated negative signal increase in cells affirming acceptable diagnostic ability of the nanocarrier. The T2 MR signal intensity for Fe3O4/CDNS-FA@CUR NPs in M109 cells was around 2-fold higher than that of MCF 10A cells. This implies two times higher selective cellular uptake of the Fe3O4/CDNS-FA@CUR NPs into M109 cell compared to MCF 10A. The multifunctional nanocarrier could be considered as promising candidate for cancer theranostics because of the smart drug release, selective cytotoxicity, suitable hemocompatibility, and proper T2 MRI contrast efficiency.


Assuntos
Materiais Revestidos Biocompatíveis , Meios de Contraste , Curcumina , Sistemas de Liberação de Medicamentos , Ácido Fólico , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita , Neoplasias , Linhagem Celular Tumoral , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Meios de Contraste/química , Meios de Contraste/farmacocinética , Meios de Contraste/farmacologia , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Ácido Fólico/química , Ácido Fólico/farmacocinética , Ácido Fólico/farmacologia , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
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