RESUMO
PURPOSES: Senescence is an inevitable and irreversible process, which may lead to loss in muscle and bone density, decline in brain volume and loss in renal clearance. Although aging is a well-known process, few studies on the consumption of nanodrugs by elderly people were performed. METHODS: We evaluated three different nanosystems: i) carbon based nanosystem (Graphene Quantum Dots, GQD), ii) polymeric nanoparticles and mesoporous silica (magnetic core mesoporous silica, MMSN). In previous studies, our group has already characterized GQD and MMSN nanoparticles by dynamic light scattering analysis, atomic force microscopy, transmission electron microscopy, X-ray diffraction, Raman analysis, fluorescence and absorbance. The polymeric nanoparticle has been characterized by AFM and DLS. All the nanosystems were radiolabeled with 99 m-Tc by. The in vivo biodistribution/tissue deposition analysis evaluation was done using elder (PN270) and young (PN90) mice injected with radioactive nanosystems. RESULTS: The nanosystems used in this study were well-formed as the radiolabeling processes were stable. Biodistribution analysis showed that there is a decrease in the uptake of the nanoparticles in elder mice when compared to young mice, showing that is necessary to increase the initial dose in elder people to achieve the same concentration when compared to young animals. CONCLUSION: The discrepancy on tissue distribution of nanosystems between young and elder individuals must be monitored, as the therapeutic effect will be different in the groups. Noteworthy, this data is an alarm that some specific conditions must be evaluated before commercialization of nano-drugs. Graphical Abstract Changes between younger and elderly individuals are undoubtedly, especially in drug tissue deposition, biodistribution and pharmacokinetics. The same thought should be applied to nanoparticles. A comprehensive analysis on how age discrepancy change the biological behavior of nanoparticles has been performed.
Assuntos
Grafite/química , Nanopartículas/química , Nanopartículas/metabolismo , Poliésteres/química , Dióxido de Silício/química , Fatores Etários , Animais , Marcação por Isótopo , Nanopartículas de Magnetita/química , Camundongos , Modelos Animais , Nanopartículas/administração & dosagem , Tamanho da Partícula , Porosidade , Propriedades de Superfície , Tecnécio/química , Distribuição TecidualRESUMO
: Nanodrugs have in recent years been a subject of great debate. In 2017 alone, almost 50 nanodrugs were approved for clinical use worldwide. Despite the advantages related to nanodrugs/nanomedicine, there is still a lack of information regarding the biological safety, as the real behavior of these nanodrugs in the body. In order to better understand these aspects, in this study, we evaluated the effect of polylactic acid (PLA) nanoparticles (NPs) and magnetic core mesoporous silica nanoparticles (MMSN), of 1000 nm and 50 nm, respectively, on human cells. In this direction we evaluated the cell cycle, cytochemistry, proliferation and tubulogenesis on tumor cells lines: from melanoma (MV3), breast cancer (MCF-7, MDA-MB-213), glioma (U373MG), prostate (PC3), gastric (AGS) and colon adenocarcinoma (HT-29) and non-tumor cell lines: from human melanocyte (NGM), fibroblast (FGH) and endothelial (HUVEC), respectively. The data showed that an acute exposure to both, polymeric nanoparticles or MMSN, did not show any relevant toxic effects on neither tumor cells nor non-tumor cells, suggesting that although nanodrugs may present unrevealed aspects, under acute exposition to human cells they are harmless.
Assuntos
Nanopartículas/toxicidade , Ciclo Celular , Proliferação de Células , Óxido Ferroso-Férrico/química , Fibroblastos/metabolismo , Fibroblastos/fisiologia , Células HT29 , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Células MCF-7 , Nanopartículas/química , Poliésteres/química , Dióxido de Silício/químicaRESUMO
Breast cancer is women's most common type of cancer, with a global rate of over 522,000 deaths per year. One of the main problems related to breast cancer relies in the early detection, as the specialized treatment. In this direction was developed, characterized and tested in vivo a smart delivery system, based on radiolabelled magnetic core mesoporous silica doped with trastuzumab as intralesional nanodrug for breast cancer imaging and possible therapy. The results showed that nanoparticles had a size of 58.9 ± 8.1 nm, with specific surface area of 872 m2/g and pore volume of 0.85 cm3/g with a pore diameter of 3.15 nm. The magnetic core mesoporous silica was efficiently labelled with 99mTc (97.5% ±0.8) and doped >98%. The cytotoxicity assay, demonstrated they are safe to use. The data were corroborated with the IC50 result of: 829.6 µg ± 43.2. The biodistribution showed an uptake by the tumour of 7.5% (systemic via) and 97.37% (intralesional) with less than 3% of these nanoparticles absorbed by healthy tissues. In a period 6-h post-injection, no barrier delimited by the tumour was crossed, corroborating the use as intralesional nanodrug.
Assuntos
Portadores de Fármacos , Nanopartículas , Dióxido de Silício , Trastuzumab , Neoplasias de Mama Triplo Negativas , Animais , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/uso terapêutico , Tamanho da Partícula , Dióxido de Silício/química , Dióxido de Silício/farmacocinética , Distribuição Tecidual , Trastuzumab/química , Trastuzumab/farmacocinética , Trastuzumab/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Nanoparticles have specific features (lipophilicity, surface charge, composition and size). Studies regarding the biological behavior of nanoparticles in diseases such diabetics and obesity are scarce. Here, we evaluated two nanoparticles: magnetic core mesoporous silica (MSN) (58â¯nm) and polycaprolactone (PCL) nanoparticle (280â¯nm) in obese mice. Changes in the biodistribution were observed, especially considering the mononuclear phagocyte system (MPS), and the visceral fat tissue. Nonetheless, our data corroborates the influence of size in the biodistribution in obese animals, supporting that smaller nanoparticles, may show a higher tissue deposition at spleen, due the associated splenomegaly and the complications arising from this state. Finally, our study demonstrated that, in obesity, probably due the low-grade inflammatory state associated with metabolic syndrome a difference in accumulation of nanoparticles was found, with profound impact in the tissue deposition of nanoparticles.
Assuntos
Nanopartículas de Magnetita/química , Obesidade/metabolismo , Poliésteres/química , Dióxido de Silício/química , Animais , Gordura Intra-Abdominal/metabolismo , Imageamento por Ressonância Magnética/métodos , Magnetismo , Masculino , Camundongos Endogâmicos C57BL , Sistema Fagocitário Mononuclear/metabolismo , Porosidade , Distribuição TecidualRESUMO
Whether in the cosmetic or as therapeutic, the use of nanoparticles has been increasing and taking on global proportion. However, there are few studies about the physical potential of long-term use or use in special conditions such as chronic, AIDS, pregnant women and other special health circumstances. In this context, the study of the mutagenicity and the transplacental passage represents an important and reliable model for the primary evaluation of potential health risks, especially maternal and child health. In this study we performed mutagenicity, cytotoxic and transplacental evaluation of magnetic core mesoporous silica nanoparticles, radiolabeled with 99mTc for determination of toxicogenic and embryonic/fetuses potential risk in animal model. Magnetic core mesoporous silica nanoparticles were produced and characterized by obtaining nanoparticles with a size of (58.9 ± 8.1 nm) in spherical shape and with intact magnetic core. The 99 m Tc radiolabeling process demonstrated high efficacy and stability in 98% yield over a period of 8 hours of stability. Mutagenicity assays were performed using Salmonella enteric serovar Typhimurium standard strains TA98, TA100 and TA102. Cytotoxicity assays were performed using WST-1. The transplacental evaluation assays were performed using the in vivo model with rats in two periods: embryonic and fetal stage. The results of both analyzes corroborate that the nanoparticles can i) generate DNA damage; ii) generate cytotoxic potential and iii) cross the transplantation barrier in both stages and bioaccumulates in both embryos and fetuses. The results suggest that complementary evaluations should be conducted in order to attest safety, efficacy and quality of nanoparticles before unrestricted approval of their use.
Assuntos
Fenômenos Magnéticos , Nanopartículas , Placenta/metabolismo , Dióxido de Silício/química , Dióxido de Silício/toxicidade , Animais , Transporte Biológico , Citotoxinas/química , Citotoxinas/metabolismo , Citotoxinas/toxicidade , Dano ao DNA , Feminino , Células Hep G2 , Humanos , Mutagênicos/química , Mutagênicos/metabolismo , Mutagênicos/toxicidade , Porosidade , Gravidez , Ratos , Ratos Wistar , Dióxido de Silício/metabolismo , Fatores de TempoRESUMO
Cancer is responsible for more than 12% of all causes of death in the world, with an annual death rate of more than 7 million people. In this scenario melanoma is one of the most aggressive ones with serious limitation in early detection and therapy. In this direction we developed, characterized and tested in vivo a new drug delivery system based on magnetic core-mesoporous silica nanoparticle that has been doped with dacarbazine and labelled with technetium 99 m to be used as nano-imaging agent (nanoradiopharmaceutical) for early and differential diagnosis and melanoma by single photon emission computed tomography. The results demonstrated the ability of the magnetic core-mesoporous silica to be efficiently (>98%) doped with dacarbazine and also efficiently labelled with 99mTc (technetium 99 m) (>99%). The in vivo test, using inducted mice with melanoma, demonstrated the EPR effect of the magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable when injected intratumorally and the possibility to be used as systemic injection too. In both cases, magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable showed to be a reliable and efficient nano-imaging agent for melanoma.
Assuntos
Dacarbazina/química , Imãs/química , Melanoma/diagnóstico por imagem , Nanopartículas/química , Dióxido de Silício/química , Tecnécio/química , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Diagnóstico Diferencial , Detecção Precoce de Câncer , Humanos , Marcação por Isótopo , Melanoma/patologia , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , PorosidadeRESUMO
The use of monoclonal antibodies (Mab) in the current medicine is increasing. Antibody-drug conjugates (ADCs) represents an increasingly and important modality for treating several types of cancer. In this area, the use of Mab associated with nanoparticles is a valuable strategy. However, the methodology used to calculate the Mab entrapment, efficiency and content is extremely expensive. In this study we developed and tested a novel very simple one-step methodology to calculate monoclonal antibody entrapment in mesoporous silica (with magnetic core) nanoparticles using the radiolabeling process as primary methodology. The magnetic core mesoporous silica were successfully developed and characterised. The PXRD analysis at high angles confirmed the presence of magnetic cores in the structures and transmission electron microscopy allowed to determine structures size (58.9⯱â¯8.1â¯nm). From the isotherm curve, a specific surface area of 872â¯m2/g was estimated along with a pore volume of 0.85â¯cm3/g and an average pore diameter of 3.15â¯nm. The radiolabeling process to proceed the indirect determination were well-done. Trastuzumab were successfully labeled (>97%) with Tc-99m generating a clear suspension. Besides, almost all the Tc-99m used (labeling the trastuzumab) remained trapped in the surface of the mesoporous silica for a period as long as 8â¯h. The indirect methodology demonstrated a high entrapment in magnetic core mesoporous silica surface of Tc-99m-traztuzumab. The results confirmed the potential use from the indirect entrapment efficiency methodology using the radiolabeling process, as a one-step, easy and cheap methodology.
Assuntos
Anticorpos Monoclonais/química , Nanopartículas/química , Tecnécio/química , Magnetismo/métodos , Microscopia Eletrônica de Transmissão/métodos , Tamanho da Partícula , Dióxido de Silício/química , Trastuzumab/químicaRESUMO
The use of nanosystems as diagnosing and therapy systems is increasing each year. There are several nanosystems available and the most prominent ones are: mesoporous silica, nanoemulsion and polymeric nanoparticles. With characteristics like low toxicology, and easy-producing process they have advantages when compared with the traditional system used, as they show specific targeting, controlled release, and higher penetration. In this study we tested three different nanocarriers (polymeric nanoparticles, nanoemulsion and mesoporous silica) containing phthalocyanineas possible PDT drugs (nanodrugs). They were tested in vitro and in vivo: cells and healthy mice, respectively, in order to understand the biological behavior and reach the initial conclusions. The results in cells showed that a dose response was observed with different concentrations of the three nanocarriers. The results in animal showed that all nanosystems have potential for application in PDT, since they were able to produce a visible effect in healthy animals.