RESUMO
Dendritic mesoporous organosilica nanoparticles (DMON) are a new class of biodegradable nanoparticles suitable for biomolecule delivery. We studied the photochemical internalization (PCI) and photodynamic therapy (PDT) of DMON to investigate new ways for DMON to escape from the endosomes-lysosomes and deliver biomolecules into the cytoplasm of cells. We added photosensitizers in the framework of DMON and found that DMON were loaded with siRNA or FVIII factor protein. We made four formulations with four different photosensitizers. The photosensitizers allowed us to perform imaging of DMON in cancer cells, but the presence of the tetrasulfide bond in the framework of DMON quenched the formation of singlet oxygen. Fortunately, one formulation allowed us to efficiently deliver proapoptotic siRNA in MCF-7 cancer cells leading to 31% of cancer cell death, without irradiation. As for FVIII protein, it was loaded in two formulations with drug-loading capacities (DLC) up to 25%. In conclusion, DMON are versatile nanoparticles capable of loading siRNA and delivering it into cancer cells, and also loading FVIII protein with good DLC. Due to the presence of tetrasulfide, it was not possible to perform PDT or PCI.
Assuntos
Nanopartículas , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , RNA Interferente Pequeno/metabolismo , Nanopartículas/química , Fotoquimioterapia/métodos , Células MCF-7 , Linhagem Celular TumoralRESUMO
(1) Background: Due to human activities, greenhouse gas (GHG) concentrations in the atmosphere are constantly rising, causing the greenhouse effect. Among GHGs, carbon dioxide (CO2) is responsible for about two-thirds of the total energy imbalance which is the origin of the increase in the Earth's temperature. (2) Methods: In this field, we describe the development of periodic mesoporous organosilica nanoparticles (PMO NPs) used to capture and store CO2 present in the atmosphere. Several types of PMO NP (bis(triethoxysilyl)ethane (BTEE) as matrix, co-condensed with trialkoxysilylated aminopyridine (py) and trialkoxysilylated bipyridine (Etbipy and iPrbipy)) were synthesized by means of the sol-gel procedure, then characterized with different techniques (DLS, TEM, FTIR, BET). A systematic evaluation of CO2 adsorption was carried out at 298 K and 273 K, at low pressure. (3) Results: The best values of CO2 adsorption were obtained with 6% bipyridine: 1.045 mmol·g-1 at 298 K and 2.26 mmol·g-1 at 273 K. (4) Conclusions: The synthetized BTEE/aminopyridine or bipyridine PMO NPs showed significant results and could be promising for carbon capture and storage (CCS) application.
Assuntos
Dióxido de Carbono , Nanopartículas , Adsorção , Aminopiridinas , Humanos , Porosidade , TemperaturaRESUMO
Periodic Mesoporous Organosilica Nanoparticles (PMONPs) are nanoparticles of high interest for nanomedicine applications. These nanoparticles are not composed of silica (SiO2). They belong to hybrid organic-inorganic systems. We considered using these nanoparticles for CO2 release as a contrast agent for High Intensity Focused Ultrasounds (HIFU). Three molecules (P1-P3) possessing two to four triethoxysilyl groups were synthesized through click chemistry. These molecules possess a tert-butoxycarbonyl (BOC) group whose cleavage in water at 90-100 °C releases CO2. Bis(triethoxysilyl)ethylene E was mixed with the molecules Pn (or not for P3) at a proportion of 90/10 to 75/25, and the polymerization triggered by the sol-gel procedure led to PMONPs. PMONPs were characterized by different techniques, and nanorods of 200-300 nm were obtained. These nanorods were porous at a proportion of 90/10, but non-porous at 75/25. Alternatively, molecules P3 alone led to mesoporous nanoparticles of 100 nm diameter. The BOC group was stable, but it was cleaved at pH 1 in boiling water. Molecules possessing a BOC group were successfully used for the preparation of nanoparticles for CO2 release. The BOC group was stable and we did not observe release of CO2 under HIFU at lysosomal pH of 5.5. The pH needed to be adjusted to 1 in boiling water to cleave the BOC group. Nevertheless, the concept is interesting for HIFU theranostic agents.
Assuntos
Nanomedicina , Nanopartículas/química , Compostos de Organossilício/química , Dióxido de Silício/química , Dióxido de Carbono/química , Química Click , Meios de Contraste/química , Portadores de Fármacos/química , Ésteres do Ácido Fórmico/química , Humanos , Nanopartículas/uso terapêutico , Nanotubos/química , Compostos de Organossilício/uso terapêutico , Porosidade , Dióxido de Silício/uso terapêuticoRESUMO
The aim of the present work is the development of highly efficient targeting molecules to specifically address mesoporous silica nanoparticles (MSNs) designed for the photodynamic therapy (PDT) of prostate cancer. We chose the strategy to develop a novel compound that allows the improvement of the targeting of the cation-independent mannose 6-phosphate receptor, which is overexpressed in prostate cancer. This original sugar, a dimannoside-carboxylate (M6C-Man) grafted on the surface of MSN for PDT applications, leads to a higher endocytosis and thus increases the efficacy of MSNs.
Assuntos
Fotoquimioterapia/métodos , Neoplasias da Próstata/metabolismo , Receptor IGF Tipo 2/metabolismo , Linhagem Celular Tumoral , Endocitose , Humanos , Masculino , Manosefosfatos/administração & dosagem , Manosefosfatos/química , Manosefosfatos/farmacologia , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/metabolismo , Dióxido de Silício/químicaRESUMO
(1) Background: Nanomedicine has recently emerged as a new area of research, particularly to fight cancer. In this field, we were interested in the vectorization of pepstatin A, a peptide which does not cross cell membranes, but which is a potent inhibitor of cathepsin D, an aspartic protease particularly overexpressed in breast cancer. (2) Methods: We studied two kinds of nanoparticles. For pepstatin A delivery, mesoporous silica nanoparticles with large pores (LPMSNs) and hollow organosilica nanoparticles (HOSNPs) obtained through the solâ»gel procedure were used. The nanoparticles were loaded with pepstatin A, and then the nanoparticles were incubated with cancer cells. (3) Results: LPMSNs were monodisperse with 100 nm diameter. HOSNPs were more polydisperse with diameters below 100 nm. Good loading capacities were obtained for both types of nanoparticles. The nanoparticles were endocytosed in cancer cells, and HOSNPs led to the best results for cancer cell killing. (4) Conclusions: Mesoporous silica-based nanoparticles with large pores or cavities are promising for nanomedicine applications with peptides.
Assuntos
Neoplasias da Mama/metabolismo , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Pepstatinas/administração & dosagem , Dióxido de Silício/química , Linhagem Celular Tumoral , Feminino , Humanos , Nanopartículas/ultraestrutura , Pepstatinas/química , PorosidadeRESUMO
(1) Background: Nanomedicine has recently emerged as a promising field, particularly for cancer theranostics. In this context, nanoparticles designed for imaging and therapeutic applications are of interest. We, therefore, studied the encapsulation of upconverting nanoparticles in mesoporous organosilica nanoparticles. Indeed, mesoporous organosilica nanoparticles have been shown to be very efficient for drug delivery, and upconverting nanoparticles are interesting for near-infrared and X-ray computed tomography imaging, depending on the matrix used. (2) Methods: Two different upconverting-based nanoparticles were synthesized with Yb3+-Er3+ as the upconverting system and NaYF4 or BaLuF5 as the matrix. The encapsulation of these nanoparticles was studied through the sol-gel procedure with bis(triethoxysilyl)ethylene and bis(triethoxysilyl)ethane in the presence of CTAB. (3) Results: with bis(triethoxysilyl)ethylene, BaLuF5: Yb3+-Er3+, nanoparticles were not encapsulated, but anchored on the surface of the obtained mesoporous nanorods BaLuF5: Yb3+-Er3+@Ethylene. With bis(triethoxysilyl)ethane, BaLuF5: Yb3+-Er3+ and NaYF4: Yb3+-Er3+nanoparticles were encapsulated in the mesoporous cubic structure leading to BaLuF5: Yb3+-Er3+@Ethane and NaYF4: Yb3+-Er3+@Ethane, respectively. (4) Conclusions: upconversion nanoparticles were located on the surface of mesoporous nanorods obtained by hydrolysis polycondensation of bis(triethoxysilyl)ethylene, whereas encapsulation occurred with bis(triethoxysilyl)ethane. The later nanoparticles NaYF4: Yb3+-Er3+@Ethane or BaLuF5: Yb3+-Er3+@Ethane were promising for applications with cancer cell imaging or X-ray-computed tomography respectively.
Assuntos
Nanopartículas/química , Compostos de Organossilício/química , Sistemas de Liberação de Medicamentos/métodos , Érbio/química , Etano/química , Fluoretos/química , Hidrólise , Nanomedicina/métodos , Nanotubos/química , Tecnologia Farmacêutica/métodos , Itérbio/química , Ítrio/químicaRESUMO
In this review, the use of mesoporous silica nanoparticles for photodynamic therapy (PDT) applications is described for the year 2017. Since the pioneering work in 2009, nanosystems involving mesoporous silica nanoparticles have gained in complexity with a sophisticated core-shell system able to perform multi-imaging and multi-therapies, not only for cancer diseases but also for anti-microbial therapy, atherosclerosis, or Alzheimer disease. Near-infrared, excitation light based on up-converting systems, X-rays or persistent luminescent systems are described for deeper tissue treatments.
Assuntos
Nanopartículas/química , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Dióxido de Silício/farmacologia , Doença de Alzheimer/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Bactérias/efeitos dos fármacos , Tamanho da Partícula , Fármacos Fotossensibilizantes/química , Porosidade , Dióxido de Silício/química , Propriedades de SuperfícieRESUMO
A two-photon photosensitizer with four triethoxysilyl groups is synthesized through the click reaction. This photosensitizer allows the design of bridged silsesquioxane (BS) nanoparticles through a sol-gel process; moreover, gold core BS shells or BS nanoparticles decorated with gold nanospheres are synthesized. An enhancement of the two-photon properties is noted with gold and the nanoparticles are efficient for two-photon imaging and two-photon photodynamic therapy of cancer cells.
Assuntos
Diagnóstico por Imagem , Ouro , Nanopartículas , Neoplasias/diagnóstico , Neoplasias/terapia , Compostos de Organossilício , Fotoquimioterapia , Fótons , Compostos de Amônio Quaternário , Triazóis , Sobrevivência Celular , Fluorescência , Humanos , Células MCF-7 , Nanopartículas/ultraestrutura , Solubilidade , Espectrometria de FluorescênciaRESUMO
The development of personalized and non-invasive cancer therapies based on new targets combined with nanodevices is a major challenge in nanomedicine. In this work, the over-expression of a membrane lectin, the cation-independent mannose 6-phosphate receptor (M6PR), was specifically demonstrated in prostate cancer cell lines and tissues. To efficiently target this lectin a mannose-6-phosphate analogue was synthesized in six steps and grafted onto the surface of functionalized mesoporous silica nanoparticles (MSNs). These MSNs were used for inâ vitro and exâ vivo photodynamic therapy to treat prostate cancer cell lines and primary cell cultures prepared from patient biopsies. The results demonstrated the efficiency of M6PR targeting for prostate cancer theranostic.
Assuntos
Biomarcadores Tumorais/antagonistas & inibidores , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Receptor IGF Tipo 2/antagonistas & inibidores , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Humanos , Masculino , Manosefosfatos/síntese química , Manosefosfatos/química , Nanopartículas/química , Nanopartículas/uso terapêutico , Tamanho da Partícula , Fotoquimioterapia , Porosidade , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Receptor IGF Tipo 2/genética , Dióxido de Silício/química , Propriedades de SuperfícieRESUMO
A therapy of cancer cells: Two-photon-triggered camptothecin delivery with nanoimpellers was studied in MCF-7 breast cancer cells. A fluorophore with a high two-photon absorption cross-section was first incorporated in the nanoimpellers. Fluorescence resonance energy transfer (FRET) from the fluorophore to the azobenzene moiety was demonstrated.
Assuntos
Compostos Azo/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Humanos , NeoplasiasRESUMO
The synthesis of core-shell magnetic mesoporous nanoparticles (MMSNs) through a phase transfer process is usually performed at the 100-250 mg scale. At the gram scale, nanoparticles without cores or with multicore systems are observed. Iron oxide core nanoparticles (IO) were synthesized through a thermal decomposition procedure of α-FeO(OH) in oleic acid. A phase transfer from chloroform to water was then performed in order to wrap the IO nanoparticles with a mesoporous silica shell through the sol-gel procedure. MMSNs were then functionalized with DTPA (diethylenetriaminepentacetic acid) and used for the separation of metal ions. Their toxicity was evaluated. The phase transfer procedure was crucial to obtaining MMSNs on a large scale. Three synthesis parameters were rigorously controlled: temperature, time and glassware. The homogeneous dispersion of MMSNs on the gram scale was successfully obtained. After functionalization with DTPA, the MMSN-DTPAs were shown to have a strong affinity for Ni ions. Furthermore, toxicity was evaluated in cells, zebrafish and seahorse cell metabolic assays, and the nanoparticles were found to be nontoxic. We developed a method of preparing MMSNs at the gram scale. After functionalization with DTPA, the nanoparticles were efficient in metal ion removal and separation; furthermore, no toxicity was noticed up to 125 µg mL-1 in zebrafish.
RESUMO
BACKGROUND: In addition to their great optical properties, nanodiamonds (NDs) have recently proved useful for two-photon-excited photodynamic therapy (TPE-PDT) applications. Indeed, they are able to produce reactive oxygen species (ROS) directly upon two-photon excitation but not with one-photon excitation; Methods: Fluorescent NDs (FNDs) with a 100 nm diameter and detonation NDs (DNDs) of 30 nm were compared. In order to use the gems for cancer-cell theranostics, they were encapsulated in a bis(triethoxysilyl)ethylene-based (ENE) periodic mesoporous organosilica (PMO) shell, and the surface of the formed nanoparticles (NPs) was modified by the direct grafting of polyethylene glycol (PEG) and amino groups using PEG-hexyltriethoxysilane and aminoundecyltriethoxysilane during the sol-gel process. The NPs' phototoxicity and interaction with MDA-MB-231 breast cancer cells were evaluated afterwards; Results: Transmission electronic microscopy images showed the formation of core-shell NPs. Infrared spectra and zeta-potential measurements confirmed the grafting of PEG and NH2 groups. The encapsulation of the NDs allowed for the imaging of cancer cells with NDs and for the performance of TPE-PDT of MDA-MB-231 cancer cells with significant mortality. CONCLUSIONS: Multifunctional ND@PMO core-shell nanosystems were successfully prepared. The NPs demonstrated high biocompatibility and TPE-PDT efficiency in vitro in the cancer cell model. Such systems hold good potential for two-photon-excited PDT applications.
RESUMO
The synthesis through click chemistry of triethoxysilylated cyclen derivative-based ligands is described. Different methods were used such as the copper catalyzed Huisgen's reaction, or thiol-ene reaction for the functionalization of the cyclen scaffold with azidopropyltriethoxysilane or mercaptopropyltriethoxysilane, respectively. These ligands were then grafted on magnetic mesoporous silica nanoparticles (MMSN) for extraction and separation of Ni(ii) and Co(ii) metal ions from model solutions. The bare and ligand-modified MMSN materials revealed high adsorption capacity (1.0-2.13 mmol g-1) and quick adsorption kinetics, achieving over 80% of the total capacity in 1-2 hours.
RESUMO
The world of biomedical research is in constant evolution, requiring more and more conditions and norms through pre-clinic and clinic studies. Nanodiamonds (NDs) with exceptional optical, thermal and mechanical properties emerged on the global scientific scene and recently gained more attention in biomedicine and bioanalysis fields. Many problematics have been deliberated to better understand their in vitro and in vivo efficiency and compatibility. Light was shed on their synthesis, modification and purification steps, as well as particle size and surface properties in order to find the most suitable operating conditions. In this review, we present the latest advances of NDs use in bioapplications. A large variety of subjects including anticancer and antimicrobial systems, wound healing and tissue engineering management tools, but also bioimaging and labeling probes are tackled. The key information resulting from these recent works were evidenced to make an overview of the potential features of NDs, with a special look on emerging therapeutic and diagnosis combinations.
Assuntos
Portadores de Fármacos/química , Desenvolvimento de Medicamentos/métodos , Nanodiamantes/química , Nanomedicina/tendências , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanodiamantes/administração & dosagem , Tamanho da Partícula , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologiaRESUMO
We report herein the preparation of mixed periodic mesoporous organosilica nanoparticles (E-Pn 75/25 and 90/10 PMO NPs) by sol-gel co-condensation of E-1,2-bis(triethoxysilyl)ethylene ((E)-BTSE or E) with previously synthesized disilylated tert-butyl 3,5-dialkoxybenzoates bearing either sulfide (precursor P1) or carbamate (precursor P2) functionalities in the linker. The syntheses were performed with cetyltrimethylammonium bromide (CTAB) as template in the presence of sodium hydroxide in water at 80 °C. The nanomaterials have been characterized by Transmission Electron Microscopy (TEM), nitrogen-sorption measurements (BET), Dynamic Light Scattering (DLS), zeta-potential, Thermogravimetric Analysis (TGA), FTIR, 13C CP MAS NMR and small angle X-ray diffraction (p-XRD). All the nanomaterials were obtained as mesoporous rodlike-shape nanoparticles. Remarkably, E-Pn 90/10 PMO NPs presented high specific surface areas ranging from 700 to 970 m2g-1, comparable or even higher than pure E PMO nanorods. Moreover, XRD analyses showed an organized porosity for E-P1 90/10 PMO NPs typical for a hexagonal 2D symmetry. The other materials showed a worm-like mesoporosity.
RESUMO
Porphyrin-based periodic mesoporous organosilica nanoparticles (PMO) synthesized from a large functional octatriethoxysilylated porphyrin precursor and allowing two-photon excitation photodynamic therapy (TPE-PDT) and NIR imaging were synthesized. These PMO were grafted with polyethylene glycol (PEG) moieties and an analogue of mannose 6-phosphate functionalized at the anomeric position (AMFA). AMFAs are known to efficiently target mannose 6-phosphate receptors (M6PRs) which are over-expressed in various cancers. Here, we demonstrated for the first time that M6PRs were over-expressed in rhabdomyosarcoma (RMS) cells and could be efficiently targeted with PMO-AMFA allowing TPE imaging and TPE-PDT of RMS cells. The comparison with healthy myoblasts demonstrated an absence of biological effects, suggesting a cancer cell specificity in the biomedical action observed.
Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Compostos de Organossilício/farmacologia , Receptor IGF Tipo 2/antagonistas & inibidores , Rabdomiossarcoma/tratamento farmacológico , Nanomedicina Teranóstica , Antineoplásicos/síntese química , Antineoplásicos/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Humanos , Nanopartículas/química , Imagem Óptica , Compostos de Organossilício/síntese química , Compostos de Organossilício/química , Tamanho da Partícula , Fotoquimioterapia , Porosidade , Porfirinas/química , Porfirinas/farmacologia , Proteômica , Receptor IGF Tipo 2/genética , Rabdomiossarcoma/diagnóstico por imagem , Rabdomiossarcoma/genética , Propriedades de Superfície , Células Tumorais CultivadasAssuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Fótons , Compostos Azo/química , Camptotecina/farmacologia , Fluorescência , Humanos , Imageamento Tridimensional , Células MCF-7 , Nanopartículas/ultraestrutura , Porosidade , Propídio/metabolismo , Dióxido de Silício/química , beta-Ciclodextrinas/químicaRESUMO
Functionalisation of MSN with mannose for PDT applications dramatically improved the efficiency of PDT on breast cancer cells.
Assuntos
Manose/química , Nanopartículas/química , Fotoquimioterapia , Dióxido de Silício/química , Apoptose , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Células HeLa , Humanos , Lectinas Tipo C/metabolismo , Manose/metabolismo , Receptor de Manose , Lectinas de Ligação a Manose/metabolismo , Estrutura Molecular , Receptores de Superfície Celular/metabolismoRESUMO
Mesoporous silica nanoparticles have unique properties: a specific large surface or a narrow casting of the sizes of pores. The perspectives of use are the creation of new tools for the premature diagnosis. For these potential biological applications, the harmlessness of these nanoparticles must be established.
Assuntos
Microscopia de Fluorescência por Excitação Multifotônica/métodos , Nanopartículas , Óptica e Fotônica , Dióxido de Silício , Nanotecnologia/métodos , Propriedades de SuperfícieRESUMO
Mesoporous organosilica nanoparticles (PHT-PMO) have been prepared from an octa-triethoxysilylated Zn phthalocyanine precursor. These PHT-PMO nanoparticles had no dark toxicity but high phototoxicity when irradiated at 650 nm, and remarkable near-infrared phototoxicity when excited at 760 and 810 nm. The PHT-PMO were then aminated to promote electrostatic complexation with siRNA. Transfection experiments were performed upon NIR irradiation and photochemical internalization was very efficient, leading to 65% luciferase extinction in MCF-7 cancer cells expressing stable luciferase.