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Sci Rep ; 10(1): 5925, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245980


The efficacy of different modalities of treating breast cancer is inhibited by several limitations such as off-targeted drug distribution, rapid drug clearance, and drug resistance. To overcome these limitations, we developed Lf-Doxo-PMNSs for combined chemo-MF-PTT. The PMNSs were synthesized by hydrothermal method and their physicochemical properties were examined by FE-SEM, TEM, DLS, TGA, XRD investigations. The cytotoxicity of as-synthesized NPs against 4T1 cells was carried out by MTT and flow cytometry assays. Afterwards, the anti-cancer activities of as-synthesized Lf-Doxo-PMNSs on the tumor status, drug distribution and apoptosis mechanism were evaluated. The anti-cancer assays showed that Lf-Doxo-PMNSs significantly suppressed the cancer cell proliferation and tumor weight by prolonging drug availability and potential drug loading in tumor cells; whereas they showed a minimum cytotoxicity against non-cancerous cells. Likewise, combined chemo-MF-PTT using Lf-Doxo-PMNSs displayed the highest anti-cancer activity followed by combined chemo-PTT and combined chemo-MF therapy based on altering the apoptosis mechanism. Therefore, these results showed that combined chemo-MF-PTT based on Lf-Doxo-PMNSs can be used as a promising therapeutic platform with potential targeted drug delivery and high loading capacity features as well as reducing cancer drug resistance.

Neoplasias da Mama/terapia , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Hipertermia Induzida/métodos , Terapia de Campo Magnético/métodos , Fotoquimioterapia/métodos , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral/transplante , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Nanopartículas de Magnetita/química , Camundongos , Nanosferas/química , Distribuição Tecidual
Talanta ; 212: 120782, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32113545


Development of optical nanobiosensors has emerged as one of the most important bioresearch areas of interest over the past decades especially in the modern innovations in the design and utilization of sensing platforms. The application of nanobiosensors has been accelerated with the introduction of plasmonic NPs, which overcome the most of the limitations in the case of conventional optical nanobiosensors. Since the plasmonic AuNPs-based nanobiosensors provide high potential achievements to develop promising platforms in fully integrated multiplex assays, some well-developed investigations are clearly required to improve the current technologies and integration of multiple signal inputs. Therefore, in this literature, we summarized the performance and achievements of optical nanobiosensors according to plasmonic rules of AuNPs, including SPR, LSPR, SERS and chiroptical phenomena. Also, we investigated the effects of the physicochemical properties of AuNPs such as size, shape, composition, and assembly on the plasmonic signal propagation in AuNPs-based nanobiosensors. Moreover, we presented an overview on the current state of plasmonic AuNPs-based nanobiosensors in the biomedical activities. Besides, this paper looks at the current and future challenges and opportunities of ongoing efforts to achieve the potential applications of AuNPs-based optical plasmonic nanobiosensors in integration with other nanomaterials. Taken together, the main focus of this paper is to provide some applicable information to develop current methodologies in fabrication of potential AuNPs-based nanobiosensors for detection of a wide range of analytes.

Mater Sci Eng C Mater Biol Appl ; 108: 110422, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924012


The utilization of AuNPs in therapeutic applications has been accelerated by discovering their catalytic activity consistent with the activity of natural enzymes. However, to reduce unwanted activities, it is imperative to fully understand their catalytic mechanisms to increase efficiency and safety. Therefore, along with other reports, we aimed to classify the enzymatic activity of Au nanozymes based on recent advance in their applications in biosensing and therapeutic activities. The results of the reported experiments indicate that the Au nanozymes can be used in biosensing of a wide range of agents such as molecule (H2O2 and glucose), ions, nucleic acids, proteins, cells, and pathogens. Furthermore, they can be used as potential candidates in inhibition of neurodegenerative diseases, cancer therapy, and antibacterial activities. Biosensing and therapeutic activities are generally based on colorimetric assays and the controlling the ROS level in the targeted cells, respectively. Finally, a brief explanation of the current challenges of the Au nanozymes in biomedical approaches was discussed. Indeed, this review holds a great promise in understanding the Au nanozymes properties and their development in biotechnology, medicine, and related industries.

Técnicas Biossensoriais/métodos , Ouro/química , Colorimetria , Nanopartículas Metálicas/química , Nanoestruturas/química , Espécies Reativas de Oxigênio/metabolismo
J Biomol Struct Dyn ; 38(12): 3676-3686, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31476976


Nickel oxide nanoparticles (NiO NPs) have received great interests in medical and biotechnological applications. However, their adverse impacts against biological systems have not been well-explored. Herein, the influence of NiO NPs on structural changes, heme degradation and aggregation of hemoglobin (Hb) was evaluated by UV-visible (Vis) spectroscopy, circular dichroism (CD) spectroscopy, fluorescence spectroscopy, transmission electron microscopy (TEM), and molecular modeling investigations. Also, the morphological changes and expression of Bax/Bcl-2 mRNA in human lymphocyte cell exposed to NiO NPs were assayed by DAPI staining and quantitative real-time PCR (qPCR), respectively. The UV-Vis study depicted that NiO NPs resulted in the displacement of aromatic residues and heme groups and production of the pro-aggregatory species. Intrinsic and Thioflavin T (ThT) fluorescence studies revealed that NiO NPs resulted in heme degradation and amorphous aggregation of Hb, respectively, which the latter result was also confirmed by TEM study. Moreover, far UV-CD study depicted that NiO NPs lead to substantial secondary structural changes of Hb. Furthermore, near UV-CD displayed that NiO NPs cause quaternary conformational changes of Hb as well as heme displacement. Molecular modelling study also approved that NiO NPs resulted in structural alterations of Hb and heme deformation. Moreover, morphological and genotoxicity assays revealed that the DNA fragmentation and expression ratio of Bax/Bcl-2 mRNA increased in lymphocyte cells treated with NiO NPs for 24 hr. In conclusion, this study indicates that NiO NPs may affect the biological media and their applications should be limited.Communicated by Ramaswamy H. Sarma.

Apoptose , Linfócitos , Nanopartículas Metálicas/toxicidade , Níquel/toxicidade , Heme , Hemoglobinas , Humanos
Int J Pharm ; 572: 118824, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31715345


In this study, we formulated silymarin-HSA nanoplex and assayed its ability to reduce LPS-induced toxicity in vitro and in vivo. Silymarin molecules were encapsulated into HSA nanoplex and the loading efficiency and characterization of fabricated nanoplex were performed by using HPLC, TEM, SEM, DLS, FTIR analysis, and theoretical studies. Afterwards, their protective effect against LPS (20 µg/ml) -induced toxicity in SH-SY5Y cells was investigated by MTT, ROS, and apoptosis assays. For in vivo experiments, rats were pre-treated with either silymarin or silymarin -HSA nanoplex (200 mg/kg) orally for 3 days and at third day received LPS by IP at a dose of 0.5 mg/kg, 150 min before scarification followed by SOD and CAT activity assay. The formulation of silymarin-HSA nanoplex showed a spherical shape with an average diameter between 50 nm and 150 nm, hydrodynamic radius of 188.3 nm, zeta potential of -26.6 mV, and a drug loading of 97.3%. In LPS-treated cells, pretreatments with silymarin-HSA noncomplex recovered the cell viability and decreased the ROS level and corresponding apoptosis more significantly than free silymarin. In rats, it was also depicted that, silymarin-HSA noncomplex can increase the SOD and CAT activity in brain tissue at LPS-triggered oxidative stress model more significantly than the free counterpart. Therefore, nanoformulation of silymarin improved its capability to reduce LPS-induced oxidative stress by restoring cell viability and elevation of SOD and CAT activity in vitro and in vivo, respectively. In conclusion, formulation of silymarin may hold a great promise in the development of antioxidant agents.

Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Albumina Sérica Humana/química , Silimarina/farmacologia , Animais , Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Lipopolissacarídeos/toxicidade , Masculino , Neuroblastoma/patologia , Tamanho da Partícula , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Silimarina/administração & dosagem