RESUMO
Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3âº-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3âº-MIH and its potential to enhance breast cancer management.
Assuntos
Neoplasias da Mama , Imageamento por Ressonância Magnética , Nanopartículas , Dióxido de Silício , Nanomedicina Teranóstica , Dióxido de Silício/química , Animais , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Nanomedicina Teranóstica/métodos , Imageamento por Ressonância Magnética/métodos , Camundongos , Linhagem Celular Tumoral , Nanopartículas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Meios de Contraste/química , Gadolínio/química , Porosidade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Some characteristics of silica-based materials, such as the control/adjustment of their physical and chemical properties, compatibility, and friendly-use synthesis methods, have held the attention of several scientific groups over the years. This condition of prominence becomes even more evident when we seek these characteristics at the micro- and/or nanoscale. Among existing methods to obtain these micro/nanomaterials, the Stöber method is the focus of this review. This method is known to enable the production of silica micro- or nanoparticles from reagents of medium-easy manipulation under mild conditions using equipment that is common in most laboratories. However, this method has many nuances that must be considered to guarantee accurate results, either in size or distribution, and to ensure result reproducibility. Thus, in this review, we discuss the effects of the primary components used in the synthesis of these materials (i.e., TEOS, ammonia, and water), as well as those of other reaction conditions, such as solvent, temperature, and ionic strength. Therefore, we discuss studies involving the synthesis and characterization of micro- and nanoparticles over the years to establish discussions between their experimental observations and proposed models. This review provides experimental observations about the synthesis of these materials, as well as discussions according to complementary and/or contradictory evidence found over the years. This review seeks to help those who intend to work with this method and provide certain key points that, in our experience, can be important to obtain desired results.
RESUMO
Protein corona formation and nanoparticles' aggregation have been heavily discussed over the past years since the lack of fine-mapping of these two combined effects has hindered the targeted delivery evolution and the personalized nanomedicine development. We present a multitechnique approach that combines dynamic light and small-angle X-ray scattering techniques with cryotransmission electron microscopy in a given fashion that efficiently distinguishes protein corona from aggregates formation. This methodology was tested using â¼25 nm model silica nanoparticles incubated with either model proteins or biologically relevant proteomes (such as fetal bovine serum and human plasma) in low and high ionic strength buffers to precisely tune particle-to-protein interactions. In this work, we were able to differentiate protein corona, small aggregates formation, and massive aggregation, as well as obtain fractal information on the aggregates reliably and straightforwardly. The strategy presented here can be expanded to other particle-to-protein mixtures and might be employed as a quality control platform for samples that undergo biological tests.
Assuntos
Nanopartículas , Coroa de Proteína , Humanos , Tamanho da Partícula , Soroalbumina Bovina , Dióxido de SilícioRESUMO
Staphylococcal enterotoxins are one of the most important causative agents of food poisoning. These molecules function as both gastrointestinal toxins and superantigens (SAgs) which can simultaneously bind MHC-II and T cell receptor leading to a non-specific polyclonal T cell activation and massive proinflammatory cytokine release. Common symptoms include vomiting and diarrhea; however, in more severe cases, systemic dissemination may result in toxic shock syndrome and can be lethal in a few hours. Only small amounts of these heat-stable toxins are needed to cause the disease. Therefore, it is highly important to detect quickly low concentrations of SAgs in biological samples. In this work, we report a surface plasmon resonance (SPR)-based capture immunoassay for the detection of the SAg SEG. We analyzed the use of different amplification strategies. The SPR-based double-antibody sandwich approach could detect picomolar levels of SEG. The use of antibody-coated silica nanoparticles (AbSiNPs) as an alternative enhancing reagent also detected SEG in the picomolar range. Although AbSiNPs did not improve the limit of detection, for the same amount of SAg tested, AbSiNPs gave a higher response level than free antibodies. This work highlights the suitability of silica nanoparticles for signal amplification in SPR-based biosensors. Overall, SPR biosensors offer the capability for continuous real-time monitoring and high sensitivity that can be befitting for the detection of enterotoxins in food industries, laboratories and regulatory agencies.
Assuntos
Enterotoxinas/análise , Imunoensaio/métodos , Superantígenos/análise , Ressonância de Plasmônio de Superfície/métodos , Sequência de Aminoácidos , Animais , Anticorpos Antibacterianos , Técnicas Biossensoriais/métodos , Materiais Revestidos Biocompatíveis , Enterotoxinas/genética , Enterotoxinas/imunologia , Microbiologia de Alimentos , Humanos , Limite de Detecção , Nanopartículas , Coelhos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Dióxido de Silício , Intoxicação Alimentar Estafilocócica/diagnóstico , Staphylococcus aureus/química , Staphylococcus aureus/genética , Staphylococcus aureus/imunologia , Superantígenos/genética , Superantígenos/imunologiaRESUMO
Tacrolimus (TAC), a potent immunosuppressive macrolide, has been investigated for ocular diseases due to promising results in the treatment of anterior and posterior segments eye diseases. Mesoporous and functionalized silica nanoparticles show potential as TAC delivery platforms owing to their interesting characteristic as large surface area, uniform pore size distribution, high pore volume, and excellent biocompatibility. The purpose of this study was to incorporate TAC in functionalized silica nanoparticles with 3-aminopropyltriethoxysilane (MSNAPTES) and investigate the safety and biocompatibility of the systems. The MSNAPTES and MSNAPTES TAC nanoparticles were characterized. The in vitro cytotoxicity of MSNAPTES and MSNAPTES load with TAC (MSNAPTES-TAC) in retinal pigment epithelial cells (ARPE-19) was determined, chorioallantoic membrane (CAM) assay model was used to investigate the in vivo biocompatibility, and safety of intravitreal injection was evaluated using clinical examination (assessment of intraocular pressure and indirect fundus ophthalmoscopy), electroretinographic (ERG) and histologic studies in rats' eyes. The elemental analysis (CHN), thermogravimetric (TGA), photon correlation spectroscopy and Fourier transform infrared (FTIR) analysis confirmed the presence of functionalized agent and TAC in the MSNAPTES nanoparticles. TAC loading was estimated at 7% for the MSNAPTES TAC nanoparticles. MSNAPTES and MSNAPTES TAC did not present in vitro cytotoxicity. The drug delivery systems showed good biocompatibility on CAM. No retinal abnormalities, vitreous hemorrhage, neovascularization, retinal detachment, and optic nerve atrophy were observed during the in vivo study. Follow-up ERGs showed no changes in the function of the retina cells after 15 days of intravitreal injection, and histopathologic observations support these findings. In conclusion, MSNAPTES TAC was successfully synthesized, and physicochemical analyses confirmed the presence of TAC in the nanoparticles. In vitro and in vivo studies indicated that MSNAPTES TAC was safe to intravitreal administration. Taking into account the enormous potential of MSNAPTES to carry TAC, this platform could be a promising strategy for TAC ocular drug delivery in the treatment of eye diseases.