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The design and synthesis of artificial materials that mimic the structures, mechanical properties, and ultimately functionalities of biological cells remains a current holy grail of materials science. Here, based on a silica cell bioreplication approach, we report the design and construction of synthetic rebuilt red blood cells (RRBCs) that fully mimic the broad properties of native RBCs: size, biconcave shape, deformability, oxygen-carrying capacity, and long circulation time. Four successive nanoscale processing steps (RBC bioreplication, layer-by-layer polymer deposition, and precision silica etching, followed by RBC ghost membrane vesicle fusion) are employed for RRBC construction. A panel of physicochemical analyses including zeta-potential measurement, fluorescence microscopy, and antibody-mediated agglutination assay proved the recapitulation of RBC shape, size, and membrane structure. Flow-based deformation studies carried out in a microfluidic blood capillary model confirmed the ability of RRBCs to deform and pass through small slits and reconstitute themselves in a manner comparable to native RBCs. Circulation studies of RRBCs conducted ex ovo in a chick embryo and in vivo in a mouse model demonstrated the requirement of both deformability and native cell membrane surface to achieve long-term circulation. To confer additional non-native functionalities to RRBCs, we developed modular procedures with which to load functional cargos such as hemoglobin, drugs, magnetic nanoparticles, and ATP biosensors within the RRBC interior to enable various functions, including oxygen delivery, therapeutic drug delivery, magnetic manipulation, and toxin biosensing and detection. Taken together, RRBCs represent a class of long-circulating RBC-inspired artificial hybrid materials with a broad range of potential applications.
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Biomimética , Preparações Farmacêuticas , Animais , Embrião de Galinha , Membrana Eritrocítica , Eritrócitos , Camundongos , MicrofluídicaRESUMO
Creating a synthetic exoskeleton from abiotic materials to protect delicate mammalian cells and impart them with new functionalities could revolutionize fields like cell-based sensing and create diverse new cellular phenotypes. Herein, the concept of "SupraCells," which are living mammalian cells encapsulated and protected within functional modular nanoparticle-based exoskeletons, is introduced. Exoskeletons are generated within seconds through immediate interparticle and cell/particle complexation that abolishes the macropinocytotic and endocytotic nanoparticle internalization pathways that occur without complexation. SupraCell formation is shown to be generalizable to wide classes of nanoparticles and various types of cells. It induces a spore-like state, wherein cells do not replicate or spread on surfaces but are endowed with extremophile properties, for example, resistance to osmotic stress, reactive oxygen species, pH, and UV exposure, along with abiotic properties like magnetism, conductivity, and multifluorescence. Upon decomplexation cells return to their normal replicative states. SupraCells represent a new class of living hybrid materials with a broad range of functionalities.
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Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Nanopartículas , Animais , Sobrevivência Celular , Citoproteção/efeitos dos fármacos , Humanos , Camundongos , Propriedades de SuperfícieRESUMO
The development of hybrid nanomaterials mimicking antifreeze proteins that can modulate/inhibit the growth of ice crystals for cell/tissue cryopreservation has attracted increasing interests. Herein, we describe the first utilization of zirconium (Zr)-based metal-organic framework (MOF) nanoparticles (NPs) with well-defined surface chemistries for the cryopreservation of red blood cells (RBCs) without the need of any (toxic) organic solvents. Distinguishing features of this cryoprotective approach include the exceptional water stability, low hemolytic activity, and the long periodic arrangement of organic linkers on the surface of MOF NPs, which provide a precise spacing of hydrogen donors to recognize and match the ice crystal planes. Five kinds of Zr-based MOF NPs, with different pore size, surface chemistry, and framework topologies, were used for the cryoprotection of RBCs. A "splat" assay confirmed that MOF NPs not only exhibited ice recrystallization inhibition activities but also acted as a "catalyst" to accelerate the melting of ice crystals. The human RBC cryopreservation tests displayed RBC recoveries of up to â¼40%, which is higher than that obtained via commonly used hydroxyethyl starch polymers. This cryopreservation approach will inspire the design and utilization of MOF-derived nanoarchitectures for the effective cryopreservation of various cell types as well as tissue samples.
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Criopreservação/métodos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Nanopartículas/química , Hemólise/efeitos dos fármacos , Humanos , Modelos Moleculares , Conformação Molecular , Propriedades de Superfície , Zircônio/químicaRESUMO
Targeted drug delivery remains at the forefront of biomedical research but remains a challenge to date. Herein, the first superassembly of nanosized metal-organic polyhedra (MOP) and their biomimetic coatings of lipid bilayers are described to synergistically combine the advantages of micelles and supramolecular coordination cages for targeted drug delivery. The superassembly technique affords unique hydrophobic features that endow individual MOP to act as nanobuilding blocks and enable their superassembly into larger and well-defined nanocarriers with homogeneous sizes over a broad range of diameters. Various cargos are controllably loaded into the MOP with high payloads, and the nanocages are then superassembled to form multidrug delivery systems. Additionally, functional nanoparticles are introduced into the superassemblies via a one-pot process for versatile bioapplications. The MOP superassemblies are surface-engineered with epidermal growth factor receptors and can be targeted to cancer cells. In vivo studies indicated the assemblies to have a substantial circulation half-life of 5.6 h and to undergo renal clearance-characteristics needed for nanomedicines.
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Portadores de Fármacos/química , Substâncias Macromoleculares/química , Metais/química , Nanopartículas/química , Compostos Organometálicos/química , Células A549 , Animais , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Receptores ErbB/química , Receptores ErbB/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Micelas , Modelos Animais , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
The progress of nanoparticle (NP)-based drug delivery has been hindered by an inability to establish structure-activity relationships in vivo. Here, using stable, monosized, radiolabeled, mesoporous silica nanoparticles (MSNs), we apply an integrated SPECT/CT imaging and mathematical modeling approach to understand the combined effects of MSN size, surface chemistry and routes of administration on biodistribution and clearance kinetics in healthy rats. We show that increased particle size from ~32- to ~142-nm results in a monotonic decrease in systemic bioavailability, irrespective of route of administration, with corresponding accumulation in liver and spleen. Cationic MSNs with surface exposed amines (PEI) have reduced circulation, compared to MSNs of identical size and charge but with shielded amines (QA), due to rapid sequestration into liver and spleen. However, QA show greater total excretion than PEI and their size-matched neutral counterparts (TMS). Overall, we provide important predictive functional correlations to support the rational design of nanomedicines.
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Nanopartículas/química , Dióxido de Silício/farmacocinética , Animais , Feminino , Meia-Vida , Cinética , Tamanho da Partícula , Porosidade , Ratos Endogâmicos F344 , Dióxido de Silício/química , Eletricidade Estática , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios XRESUMO
In this review, we highlight the design of nanomaterials for two-photon excitation, in order to treat tumors with a high accuracy. Indeed two-photon excitation allows remote control of the nanoparticles with a spatio-temporal resolution. The nanomaterials are based on mesoporous silica-organosilica nanoparticles including core-shell systems. The therapeutic treatments include drug delivery, photodynamic therapy, gene silencing, and their combinations. At first, the nanosystems designed for two-photon-triggered cytotoxic drug delivery are reviewed. Then the nanomaterials prepared for two-photon photodynamic therapy and reactive oxygen species delivery are discussed. Finally, the nanosystems combining drug delivery or gene silencing with two-photon photodynamic therapy are presented. Due to the rapid progresses concerning two-photon-excited nanomaterials and the interest of near-infrared light to treat deep tumors, we believe this technology could be of high interest for the personalized medicine of the future.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fótons , Dióxido de Silício/química , Inativação Gênica , Humanos , Raios Infravermelhos , Porosidade , Espécies Reativas de Oxigênio/administração & dosagemRESUMO
Silica-based nanomaterials are extensively used in industrial applications and academic biomedical research, thus properly assessing their toxicity and biodegradability is essential for their safe and effective formulation and use. Unfortunately, there is often a lot of confusion in the literature with respect to the toxicity and biodegradability of silica since various studies have yielded contradictory results. In this contribution, we first endeavor to underscore that the simplistic model of silica should be discarded in favor of a more realistic model recognizing that all silicas are not created equal and should thus be considered in the plural as silicas and silica hybrids, which indeed hold various biocompatibility and biodegradability profiles. We then demonstrated that all silicas are-as displayed in Nature-degradable in water by dissolution, as governed by the laws of kinetics. Lastly, we explore the vast potential of tuning the degradability of silica by materials design using various silica hybrids for redox-, pH-, enzymatic-, and biochelation-mediated lysis mechanisms.
Assuntos
Nanopartículas/química , Nanopartículas/metabolismo , Dióxido de Silício/química , Dióxido de Silício/metabolismo , Cinética , Solubilidade , Água/químicaRESUMO
New therapy development is critically needed for ovarian cancer. We used the chicken egg CAM assay to evaluate efficacy of anticancer drug delivery using recently developed biodegradable PMO (periodic mesoporous organosilica) nanoparticles. Human ovarian cancer cells were transplanted onto the CAM membrane of fertilized eggs, resulting in rapid tumor formation. The tumor closely resembles cancer patient tumor and contains extracellular matrix as well as stromal cells and extensive vasculature. PMO nanoparticles loaded with doxorubicin were injected intravenously into the chicken egg resulting in elimination of the tumor. No significant damage to various organs in the chicken embryo occurred. In contrast, injection of free doxorubicin caused widespread organ damage, even when less amount was administered. The lack of toxic effect of nanoparticle loaded doxorubicin was associated with specific delivery of doxorubicin to the tumor. Furthermore, we observed excellent tumor accumulation of the nanoparticles. Lastly, a tumor could be established in the egg using tumor samples from ovarian cancer patients and that our nanoparticles were effective in eliminating the tumor. These results point to the remarkable efficacy of our nanoparticle based drug delivery system and suggests the value of the chicken egg tumor model for testing novel therapies for ovarian cancer.
Assuntos
Bioensaio , Membrana Corioalantoide , Doxorrubicina , Portadores de Fármacos , Modelos Biológicos , Nanopartículas , Neoplasias Ovarianas , Animais , Linhagem Celular Tumoral , Embrião de Galinha , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Feminino , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologiaRESUMO
The original version of this Article contained an error in the spelling of the author Stanley S. Chou, which was incorrectly given as Stan Chou. This has now been corrected in both the PDF and HTML versions of the Article.
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The limited flux and selectivities of current carbon dioxide membranes and the high costs associated with conventional absorption-based CO2 sequestration call for alternative CO2 separation approaches. Here we describe an enzymatically active, ultra-thin, biomimetic membrane enabling CO2 capture and separation under ambient pressure and temperature conditions. The membrane comprises a ~18-nm-thick close-packed array of 8 nm diameter hydrophilic pores that stabilize water by capillary condensation and precisely accommodate the metalloenzyme carbonic anhydrase (CA). CA catalyzes the rapid interconversion of CO2 and water into carbonic acid. By minimizing diffusional constraints, stabilizing and concentrating CA within the nanopore array to a concentration 10× greater than achievable in solution, our enzymatic liquid membrane separates CO2 at room temperature and atmospheric pressure at a rate of 2600 GPU with CO2/N2 and CO2/H2 selectivities as high as 788 and 1500, respectively, the highest combined flux and selectivity yet reported for ambient condition operation.
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Coherent two-photon-excited (TPE) therapy in the near-infrared (NIR) provides safer cancer treatments than current therapies lacking spatial and temporal selectivities because it is characterized by a 3D spatial resolution of 1 µm3 and very low scattering. In this review, the principle of TPE and its significance in combination with organosilica nanoparticles (NPs) are introduced and then studies involving the design of pioneering TPE-NIR organosilica nanomaterials are discussed for bioimaging, drug delivery, and photodynamic therapy. Organosilica nanoparticles and their rich and well-established chemistry, tunable composition, porosity, size, and morphology provide ideal platforms for minimal side-effect therapies via TPE-NIR. Mesoporous silica and organosilica nanoparticles endowed with high surface areas can be functionalized to carry hydrophobic and biologically unstable two-photon absorbers for drug delivery and diagnosis. Currently, most light-actuated clinical therapeutic applications with NPs involve photodynamic therapy by singlet oxygen generation, but low photosensitizing efficiencies, tumor resistance, and lack of spatial resolution limit their applicability. On the contrary, higher photosensitizing yields, versatile therapies, and a unique spatial resolution are available with engineered two-photon-sensitive organosilica particles that selectively impact tumors while healthy tissues remain untouched. Patients suffering pathologies such as retinoblastoma, breast, and skin cancers will greatly benefit from TPE-NIR ultrasensitive diagnosis and therapy.
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Sistemas de Liberação de Medicamentos/métodos , Nanopartículas , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Dióxido de Silício , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Porosidade , Dióxido de Silício/química , Dióxido de Silício/uso terapêuticoRESUMO
Predetermining the physico-chemical properties, biosafety, and stimuli-responsiveness of nanomaterials in biological environments is essential for safe and effective biomedical applications. At the forefront of biomedical research, mesoporous silica nanoparticles and mesoporous organosilica nanoparticles are increasingly investigated to predict their biological outcome by materials design. In this review, it is first chronicled that how the nanomaterial design of pure silica, partially hybridized organosilica, and fully hybridized organosilica (periodic mesoporous organosilicas) governs not only the physico-chemical properties but also the biosafety of the nanoparticles. The impact of the hybridization on the biocompatibility, protein corona, biodistribution, biodegradability, and clearance of the silica-based particles is described. Then, the influence of the surface engineering, the framework hybridization, as well as the morphology of the particles, on the ability to load and controllably deliver drugs under internal biological stimuli (e.g., pH, redox, enzymes) and external noninvasive stimuli (e.g., light, magnetic, ultrasound) are presented. To conclude, trends in the biomedical applications of silica and organosilica nanovectors are delineated, such as unconventional bioimaging techniques, large cargo delivery, combination therapy, gaseous molecule delivery, antimicrobial protection, and Alzheimer's disease therapy.
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Nanomedicina , Nanopartículas/química , Dióxido de Silício/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Hemólise/efeitos dos fármacos , Humanos , Porosidade , Coroa de Proteína/química , Distribuição TecidualRESUMO
AIM: Improving the delivery of siRNA into cancer cells via bubble liposomes. Designing a thermoresponsive pegylated liposome through the introduction of ammonium bicarbonate salt into liposomes so as to control their endosomal escape for gene therapy. METHODS: A sub-200 nm nanovector was fully characterized and examined for cellular uptake, cytotoxicity, endosomal escape and gene silencing. RESULTS: The siRNA-liposomes were internalized into cancer cells within 5 min and then released siRNAs in the cytosol prior to lysosomal degradation upon external temperature elevation. This was confirmed by confocal bioimaging and gene silencing reaching up to 90% and further demonstrated by the protein inhibition of both target genes. CONCLUSION: The thermoresponsiveness of ammonium bicarbonate containing liposomes enabled the rapid endosomal escape of the particles and resulted in an efficient gene silencing.
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Healthcare-associated infections (HAIs) are the infections that patients get while receiving medical treatment in a medical facility with bacterial HAIs being the most common. Silver and gold nanoparticles (NPs) have been successfully employed as antibacterial motifs; however, NPs leaching in addition to poor dispersion and overall reproducibility are major hurdles to further product development. In this study, the authors design and fabricate a smart antibacterial mixed-matrix membrane coating comprising colloidal lysozyme-templated gold nanoclusters as nanofillers in poly(ethylene oxide)/poly(butylene terephthalate) amphiphilic polymer matrix. Mesoporous silica nanoparticles-lysozyme functionalized gold nanoclusters disperse homogenously within the polymer matrix with no phase separation and zero NPs leaching. This mixed-matrix coating can successfully sense and inhibit bacterial contamination via a controlled release mechanism that is only triggered by bacteria. The system is coated on a common radiographic dental imaging device (photostimulable phosphor plate) that is prone to oral bacteria contamination. Variation and eventually disappearance of the red fluorescence surface under UV light signals bacterial infection. Kanamycin, an antimicrobial agent, is controllably released to instantly inhibit bacterial growth. Interestingly, the quality of the images obtained with these coated surfaces is the same as uncoated surfaces and thus the safe application of such smart coatings can be expanded to include other medical devices without compromising their utility.
Assuntos
Infecções Bacterianas , Materiais Revestidos Biocompatíveis , Coloide de Ouro , Canamicina , Muramidase , Nanopartículas/química , Dióxido de Silício , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Coloide de Ouro/química , Coloide de Ouro/farmacologia , Humanos , Canamicina/química , Canamicina/farmacologia , Células MCF-7 , Muramidase/química , Muramidase/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologiaRESUMO
The biorelated degradability and clearance of siliceous nanomaterials have been questioned worldwide, since they are crucial prerequisites for the successful translation in clinics. Typically, the degradability and biocompatibility of mesoporous silica nanoparticles (MSNs) have been an ongoing discussion in research circles. The reason for such a concern is that approved pharmaceutical products must not accumulate in the human body, to prevent severe and unpredictable side-effects. Here, the biorelated degradability and clearance of silicon and silica nanoparticles (NPs) are comprehensively summarized. The influence of the size, morphology, surface area, pore size, and surface functional groups, to name a few, on the degradability of silicon and silica NPs is described. The noncovalent organic doping of silica and the covalent incorporation of either hydrolytically stable or redox- and enzymatically cleavable silsesquioxanes is then described for organosilica, bridged silsesquioxane (BS), and periodic mesoporous organosilica (PMO) NPs. Inorganically doped silica particles such as calcium-, iron-, manganese-, and zirconium-doped NPs, also have radically different hydrolytic stabilities. To conclude, the degradability and clearance timelines of various siliceous nanomaterials are compared and it is highlighted that researchers can select a specific nanomaterial in this large family according to the targeted applications and the required clearance kinetics.
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This work describes the sol-gel syntheses of para-substituted phenylene-bridged periodic mesoporous organosilica (PMO) nanoparticles (NPs) with tunable morphologies ranging from nanowires to nanospheres. The findings show the key role of the addition of organic co-solvents in the aqueous templates on the final morphologies of PMO NPs. Other factors such as the temperature, the stirring speed, and the amount of organic solvents also influence the shape of PMO NPs. The tuning of the shape of the PMO nanomaterials made it possible to study the influence of the particle morphology on the cellular internalization and biocompatibility.
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Engineering and scaling-up new materials for better water desalination are imperative to find alternative fresh water sources to meet future demands. Herein, the fabrication of hydrophobic poly(ether imide) composite nanofiber membranes doped with novel ethylene-pentafluorophenylene-based periodic mesoporous organosilica nanoparticles is reported for enhanced and fouling resistant membrane distillation. Novel organosilica nanoparticles were homogeneously incorporated into electrospun nanofiber membranes depicting a proportional increase of hydrophobicity to the particle contents. Direct contact membrane distillation experiments on the organosilica-doped membrane with only 5% doping showed an increase of flux of 140% compared to commercial membranes. The high porosity of organosilica nanoparticles was further utilized to load the eugenol antimicrobial agent which produced a dramatic enhancement of the antibiofouling properties of the membrane of 70% after 24 h.
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The delivery of large cargos of diameter above 15nm for biomedical applications has proved challenging since it requires biocompatible, stably-loaded, and biodegradable nanomaterials. In this study, we describe the design of biodegradable silica-iron oxide hybrid nanovectors with large mesopores for large protein delivery in cancer cells. The mesopores of the nanomaterials spanned from 20 to 60nm in diameter and post-functionalization allowed the electrostatic immobilization of large proteins (e.g. mTFP-Ferritin, ~534kDa). Half of the content of the nanovectors was based with iron oxide nanophases which allowed the rapid biodegradation of the carrier in fetal bovine serum and a magnetic responsiveness. The nanovectors released large protein cargos in aqueous solution under acidic pH or magnetic stimuli. The delivery of large proteins was then autonomously achieved in cancer cells via the silica-iron oxide nanovectors, which is thus a promising for biomedical applications.
Assuntos
Sistemas de Liberação de Medicamentos , Compostos Férricos , Ferritinas , Proteínas de Fluorescência Verde , Nanocompostos , Dióxido de Silício , Compostos Férricos/administração & dosagem , Compostos Férricos/química , Ferritinas/administração & dosagem , Ferritinas/química , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/química , Proteínas de Fluorescência Verde/administração & dosagem , Proteínas de Fluorescência Verde/química , Células HeLa , Humanos , Fenômenos Magnéticos , Nanocompostos/administração & dosagem , Nanocompostos/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Porosidade , Propilaminas/administração & dosagem , Propilaminas/química , Dióxido de Silício/administração & dosagem , Dióxido de Silício/químicaRESUMO
Organic-inorganic hybrid materials garner properties from their organic and inorganic matrices as well as synergistic features, and therefore have recently attracted much attention at the nanoscale. Non-porous organosilica hybrid nanomaterials with a high organic content such as silsesquioxanes (R-SiO1.5, with R organic groups) and bridged silsesquioxanes (O1.5Si-R-SiO1.5) are especially attractive hybrids since they provide 20 to 80 weight percent of organic functional groups in addition to the known chemistry and stability of silica. In the organosilica family, silsesquioxanes (R-SiO1.5) stand between silicas (SiO2) and silicones (R2SiO), and are variously called organosilicas, ormosil (organically-modified silica), polysilsesquioxanes and silica hybrids. Herein, we comprehensively review non-porous silsesquioxane and bridged silsesquioxane nanomaterials and their applications in nanomedicine, electro-optics, and catalysis.
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We describe biodegradable mesoporous hybrid nanoparticles (NPs) in the presence of proteins and their applications for drug delivery. We synthesized oxamide phenylene-based mesoporous organosilica nanoparticles (MON) in the absence of a silica source which had remarkably high organic content and high surface areas. Oxamide functions provided biodegradability in the presence of trypsin model proteins. MON displayed exceptionally high payloads of hydrophilic and hydrophobic drugs (up to 84â wt %), and a unique zero premature leakage without the pore capping, unlike mesoporous silica. MON were biocompatible and internalized into cancer cells for drug delivery.