Monodisperse magnetic nanoparticles for theranostic applications

Effective medical care requires the concurrent monitoring of medical treatment. The combination of imaging and therapeutics allows a large degree of control over the treatment efficacy and is now commonly referred to as "theranostics". Magnetic nanoparticles (NPs) provide a unique nanoplatform for theranostic applications because of their biocompatibility, their responses to the external magnetic field, and their sizes which are comparable to that of functional biomolecules. Recent studies of magnetic NPs for both imaging and therapeutic applications have led to greater control over size, surface functionalization, magnetic properties, and specific binding capabilities of the NPs. The combination of the deep tissue penetration of the magnetic field and the ability of magnetic NPs to enhance magnetic resonance imaging sensitivity and magnetic heating efficiency makes magnetic NPs promising candidates for successful future theranostics. In this Account, we review recent advances in the synthesis of magnetic NPs for biomedical applications such as magnetic resonance imaging (MRI) and magnetic fluid hyperthermia (MFH). Our focus is on iron oxide (Fe(3)O(4)) NPs, gold-iron oxide (Au-Fe(3)O(4)) NPs, metallic iron (Fe) NPs, and Fe-based alloy NPs, such as iron-cobalt (FeCo) and iron-platinum (FePt) NPs. Because of the ease of fabrication and their approved clinical usage, Fe(3)O(4) NPs with controlled sizes and surface chemistry have been studied extensively for MRI and MFH applications. Porous hollow Fe(3)O(4) NPs are expected to have similar magnetic, chemical, and biological properties as the solid Fe(3)O(4) NPs, and their structures offer the additional opportunity to store and release drugs at a target. The Au-Fe(3)O(4) NPs combine both magnetically active Fe(3)O(4) and optically active Au within one nanostructure and are a promising NP platform for multimodal imaging and therapeutics. Metallic Fe and FeCo NPs offer the opportunity for probes with even higher magnetizations. However, metallic NPs are normally very reactive and are subject to fast oxidation in biological solutions. Once they are coated with a layer of polycrystalline Fe(3)O(4) or a graphitic shell, these metallic NPs are more stable and provide better contrast for MRI and more effective heating for MFH. FePt NPs are chemically more stable than Fe and FeCo NPs and have shown great potential as contrast agents for both MRI and X-ray computed tomography (CT) and as robust probes for controlled heating in MFH.     

中空介孔氧化硅纳米颗粒的制备及应用进展

集空腔与介孔结构于一体的中空介孔氧化硅纳米材料(HMSNs)因其高比表面积、可调孔径、低密度和高渗透等特性,而在诸多领域展现了极大的潜在应用前景。该文对中空-介孔氧化硅纳米颗粒的主要制备方法及其优缺点进行了概述,着重阐述了硬核模板法、液体界面组装法和界面重组与转换法的研究进展;同时,介绍了中空介孔氧化硅纳米颗粒在生物医药、催化和光学领域方面的应用。最后,对其制备和应用目前存在的挑战以及后续突破方向进行了分析和展望。     

中空介孔氧化硅纳米颗粒的制备及应用进展

集空腔与介孔结构于一体的中空介孔氧化硅纳米颗粒因其高比表面积、可调孔径、低密度和高渗透等特性,而在诸多领域展现了极大的潜在应用前景。本文对中空-介孔氧化硅纳米颗粒的主要制备方法及其优缺点进行了概述,着重阐述了硬核模板法、液体界面组装法和界面重组与转换法;同时介绍了中空介孔氧化硅纳米颗粒在生物医药、催化和光学领域的应用情况。最后,对其制备和应用存在的挑战和研究方向进行了分析和展望。     

Biodegradability of mesoporous silica nanoparticles

Biodegradability significantly impacts the bioapplication of mesoporous silica nanoparticles (MSN). In recent years, immense efforts have been made to understand and tailor the biodegradability of MSN. In this mini review, we overview the recent reports on the biodegradation of MSN, with a focus on the correlation between biodegradation and physicochemical properties including specific surface area, morphology, pore size, particle diameter and condensation degree of silicon-oxygen network. In addition, strategies for improving the biodegradability of MSN such as metal ions and organic species doping are also introduced.     

Surface-functionalized mesoporous silica nanoparticles as sorbents for BTEX

A series of octyl-functionalized and surfactant-containing mesoporous silica nanoparticle (MSN) materials were synthesized via a co-condensation method. The authors investigated the feasibility of the MSN materials as adsorbents for BTEX (benzene, toluene, ethylbenzene, and xylenes) in groundwater. Octyl group functionalization up to 1.5 mol octyl/kg MSN improved BTEX adsorption capacity, while the mesoporous structure was still maintained. The following trend in adsorption equilibrium and kinetics of each BTEX compound onto MSN was observed: p-xylene > ethylbenzene > = toluene > benzene. Pseudo-second-order rate constant for p-xylene adsorption onto MSN was 0.907 g/mmol.min, significantly higher than that of activated carbon (0.043 g/mol.min). Desorption/regeneration with methanol was completed in 2 h, and the regenerated MSN showed the adsorption capability equivalent to the original. We envision that the MSN material could serve as an efficient adsorbent for the removal of BTEX from aqueous phase.     

Mechanized silica nanoparticles: a new frontier in theranostic nanomedicine

Medicine can benefit significantly from advances in nanotechnology because nanoscale assemblies promise to improve on previously established therapeutic and diagnostic regimes. Over the past decade, the use of delivery platforms has attracted attention as researchers shift their focus toward new ways to deliver therapeutic and/or diagnostic agents and away from the development of new drug candidates. Metaphorically, the use of delivery platforms in medicine can be viewed as the "bow-and-arrow" approach, where the drugs are the arrows and the delivery vehicles are the bows. Even if one possesses the best arrows that money can buy, they will not be useful if one does not have the appropriate bow to deliver the arrows to their intended location. Currently, many strategies exist for the delivery of bioactive agents within living tissue. Polymers, dendrimers, micelles, vesicles, and nanoparticles have all been investigated for their use as possible delivery vehicles. With the growth of nanomedicine, one can envisage the possibility of fabricating a theranostic vector that could release powerful therapeutics and diagnostic markers simultaneously and selectively to diseased tissue. In our design of more robust theranostic delivery systems, we have focused our attention on using mesoporous silica nanoparticles (SNPs). The payload "cargo" molecules can be stored within this robust domain, which is stable to a wide range of chemical conditions. This stability allows SNPs to be functionalized with stimulus-responsive mechanically interlocked molecules (MIMs) in the shape of bistable rotaxanes and psuedorotaxanes to yield mechanized silica nanoparticles (MSNPs). In this Account, we chronicle the evolution of various MSNPs, which came about as a result of our decade-long collaboration, and discuss advances in the synthesis of novel hybrid SNPs and the various MIMs which have been attached to their surfaces. These MIMs can be designed in such a way that they either change shape or shed off some of their parts in response to a specific stimulus, such as changes in redox potential, alterations in pH, irradiation with light, or the application of an oscillating magnetic field, allowing a theranostic payload to be released from the nanopores to a precise location at the appropiate time. We have also shown that these integrated systems can operate not only within cells, but also in live animals in response to pre-existing biological triggers. Recognizing that the theranostics of the future could offer a fresh approach to the treatment of degenerative diseases including cancer, we aim to start moving out of the chemical domain and into the biological one. Some MSNPs are already being tested in biological systems.     

负载羧基化球状介孔纳米颗粒TFN膜的研究

在薄层复合膜(thin-film composite membrane, TFC膜)中引入无机纳米颗粒,形成薄层纳米复合膜(thin-film nanocomposite membrane, TFN膜),近几年作为反渗透膜开始应用于水处理研究。但是无机纳米颗粒在TFC膜中的性能的不稳定性和膜的机械强度等变成了突出问题。合成制备了粒径约为110 nm修饰羧基的介孔氧化硅球状纳米颗粒(MSN—COOH),并将其成功地化学键合在TFC膜的表面功能层交联网络中。与TFC膜相比,键合有MSN—COOH的TFN膜,水通量提高了56.2%,保持高脱盐率;由于单分散介孔纳米颗粒表面亲水官能团的引入,使膜表面的亲水性有很大程度提高,单分散介孔纳米颗粒在基体中的有序排列,使膜表面粗糙度降低,提高了膜的抗污染能力。与普通TFN膜相比较,具有更好的稳定性和柔韧性,可以在长时间高压过滤操作下保持稳定。     

PEG-templated mesoporous silica nanoparticles exclusively target cancer cells

Mesoporous silica nanoparticles (MSNs) have been proposed as DNA and drug delivery carriers, as well as efficient tools for fluorescent cell tracking. The major limitation is that MSNs enter cells regardless of a target-specific functionalization. Here we show that non functionalized MSNs, synthesized using a PEG surfactant-based interfacial synthesis procedure, do not enter cells, while a highly specific, receptor mediated, cellular internalization of folic acid (FOL) grafted MSNs (MSN-FOL), occurs exclusively in folate receptor (FR) expressing cells. Neither the classical clathrin pathway nor macropinocytosis is involved in the MSN endocytic process, while fluorescent MSNs (MSN-FITC) enter cells through aspecific, caveolae-mediated, endocytosis. Moreover, internalized particles seem to be mostly exocytosed from cells within 96 h. Finally, cisplatin (Cp) loaded MSN-FOL were tested on cancerous FR-positive (HeLa) or normal FR-negative (HEK293) cells. A strong growth arrest was observed only in HeLa cells treated with MSN-FOL-Cp. The results presented here show that our mesoporous nanoparticles do not enter cells unless opportunely functionalized, suggesting that they could represent a promising vehicle for drug targeting applications.     

Preparation of mesoporous benzene–silica nanoparticles

Nanoparticles of periodic mesoporous organosilica (PMO) with benzene bridging groups were prepared using a 1,4-bis(triethoxysilyl)benzene organosilica precursor and mixed surfactant templates composed of a poly(ethylene oxide)–poly(dl-lactic acid-co-glycolic acid)–poly(ethylene oxide) (PEO–PLGA–PEO) triblock copolymer and a fluorocarbon surfactant under acidic conditions. Mesoporous organosilica particles clearly exhibited a nanoscale diameter of 50–1000 nm by scanning electron microscopy. Moreover, these particles possessed a mesostructure with uniform pores in the range of 6.3–6.6 nm and core-shell type spherical morphology, which were confirmed by Synchrotron small angle X-ray scattering, transmission electron microscopy, and nitrogen adsorption analysis. Benzene bridging groups linked covalently to Si atoms were analyzed by solid state ¹³C- and ²⁹Si MAS NMR.     

Preparation and anticorrosion resistance of a self-curing epoxy nanocomposite coating based on mesoporous silica nanoparticles loaded with perfluorooctyl triethoxysilane

Organic coatings are prone to failure due to diffusion of the corrosion media toward the metal surface through the microcracks caused by internal and environmental stresses especially in immersion environment. In order to extend the service lifetime of organic coatings, we developed a self-curing epoxy resin/perfluorooctyl triethoxysilane (POTS)-loaded mesoporous silica nanoparticles (MSNs) nanocomposite (SEP/POTS-MSNs) coating, by embedding the POTS-loaded MSNs (POTS-MSNs) into an SEP resin. Fourier transform infrared, X-ray photoelectron spectroscopy, and Brunauer–Emmett–Teller analyses were conducted to confirm the successful loading of POTS in the MSNs. Thermogravimetric analysis was used to characterize the loading amount of POTS. The corrosion protection properties of the SEP, SEP/MSNs, and SEP/POTS-MSNs coatings were evaluated by electrochemical impedance spectroscopy and potentiodynamic polarization tests. The results indicate that the SEP/POTS-MSNs coating with only 30 μm thickness showed corrosion resistance with Z _{f = 0.01 Hz} of 4.7 × 10⁸ Ω/cm² and i_corr of 0.026 nA/cm² after 58 hr of immersion in boiling water, which were both two orders of magnitude higher than those of the SEP coating. The SEP/POTS-MSNs coating combines the advantages of the SEP coating and the POTS-MSNs. We anticipate that the SEP/POTS-MSNs coating has promising potential for use in immersion environments.     

Adsorption and release of biocides with mesoporous silica nanoparticles

In this proof-of-concept study, an agricultural biocide (imidacloprid) was effectively loaded into the mesoporous silica nanoparticles (MSNs) with different pore sizes, morphologies and mesoporous structures for termite control. This resulted in nanoparticles with a large surface area, tunable pore diameter and small particle size, which are ideal carriers for adsorption and controlled release of imidacloprid. The effect of pore size, surface area and mesoporous structure on uptake and release of imidacloprid was systematically studied. It was found that the adsorption amount and release profile of imidacloprid were dependent on the type of mesoporous structure and surface area of particles. Specifically, MCM-48 type mesoporous silica nanoparticles with a three dimensional (3D) open network structure and high surface area displayed the highest adsorption capacity compared to other types of silica nanoparticles. Release of imidacloprid from these nanoparticles was found to be controlled over 48 hours. Finally, in vivo laboratory testing on termite control proved the efficacy of these nanoparticles as delivery carriers for biopesticides. We believe that the present study will contribute to the design of more effective controlled and targeted delivery for other biomolecules.     

Multistimuli responsive polymeric nanosystems for theranostic applications

This article describes the synthesis, and characterization of two novel multistimuli responsive polymeric nanosystems for theranostic applications. For this purpose, the poly(N-isopropylacrylamide-co-itaconic anhydride) [P(NIPAAm-co-IA)] copolymer was synthesized by a free radical initiated polymerization method, and subsequently a macrobranched terpolymer was synthesized by partial esterification of P(NIPAAm-co-IA) copolymer with monomethoxy poly(ethylene glycol) [PNIPAAm-co-(PIA-g-PEG)]. This terpolymer with carboxylic functional groups adsorbed onto the surface of Fe₃O₄ nanoparticles (MNHG (1)). In another experimental process the PEG end-capped itaconat macromonomer (PEGIAM) was adsorbed onto the surface of Fe₃O₄ nanoparticles, and then copolymerized with NIPAAm via a free radical initiated polymerization technique (MNHG (2)). The chemical structures of all samples as representatives were characterized by means of FTIR and ¹H NMR spectroscopies. The LCST, morphologies, elemental compositions, and magnetic properties of the synthesized MNHGs were examined. The potential cytotoxic effects of the MNHGs were evaluated by MTT assay. According to the results, we envision that the synthesized MNHGs may be find theranostic applications, in part due to their smart physicochemical properties.     

Molecular imaging with theranostic nanoparticles

Nanoparticles (NPs) offer diagnostic and therapeutic capabilities not available with small molecules or microscale tools. As the field of molecular imaging has emerged from the blending of molecular biology with medical imaging, NP imaging is increasingly common for both therapeutic and diagnostic applications. The term theranostic describes technology with concurrent and complementary diagnostic and therapeutic capabilities. Although NPs have been FDA-approved for clinical use as transport vehicles for nearly 15 years, full translation of their theranostic potential is incomplete. However, NPs have shown remarkable success in the areas of drug delivery and magnetic resonance imaging. Emerging applications include image-guided resection, optical/photoacoustic imaging in vivo, contrast-enhanced ultrasound, and thermoablative therapy. Diagnosis with NPs in molecular imaging involves the correlation of the signal with a phenotype. The location and intensity of NP signals emanating from a living subject indicate the disease area's size, stage, and biochemical signature. Therapy with NPs uses the image for resection or delivery of a small molecule or RNA therapeutic. Ablation of the affected area is also possible via heat or radioactivity. The ideal theranostic NP includes several features: (1) it selectively and rapidly accumulates in diseased tissue; (2) it reports biochemical and morphological characteristics of the area; (3) it delivers an effective therapeutic; and (4) it is safe and biodegrades with nontoxic byproducts. Such a system contains a central imaging core surrounded by small molecule therapeutics. The system targets via ligands such as IgG and is protected from immune scavengers by a cloak of protective polymer. Although no NP has achieved all of the above criteria, many NPs possess one or more of these features. While the most clinically translatable NPs have been used in the field of magnetic resonance imaging, other types in development are quickly becoming more biocompatible through methods that modify their toxicity and biodistribution profiles. In this Account, we describe diagnostic imaging and therapeutic uses of NPs. We propose and offer examples of five primary types of nanoparticles with concurrent diagnostic and therapeutic uses.     

Amino-functionalized mesoporous silica nanoparticles: adsorption and protection for pcDNA3.1(+)-PKB-HA

This work evaluated the adsorption and protection capacities of amino-functionalized mesoporous silica nanoparticles (Am-MSNs) for the recombinant DNA (rDNA), pcDNA3.1(+)-PKB-HA. The in vitro biocompatibility of Am-MSNs was also tested on HeLa and A549 cells, respectively. The results reveal that the MSNs modified with 3-aminopropyltriethoxysilane exhibit good adsorption capacity for pcDNA3.1(+)-PKB-HA at physiological conditions and the adsorption amount is higher than that of other silica nanoparticles. Moreover, the material can also protect pcDNA3.1(+)-PKB-HA from enzymatic degradation completely and presents high in vitro biocompatibility. This demonstrates that Am-MSNs may be potential nonviral vector candidates for pcDNA3.1(+)-PKB-HA.     

Tuning biodegradability and biocompatibility of mesoporous silica nanoparticles by doping strontium

Mesoporous silica nanoparticle (MSN), one of the most widely used nanomaterials, is of poor biodegradability in vivo due to its highly stable Si–O–Si structure. Here, the structural stability of Si–O–Si was regulated by doping strontium ion. Sr-doped MSNs (Sr-MSNs) were synthesized by a cetyltrimethylammonium-bromide-mediated template method and their phase, morphology, structure, physicochemical properties, in vitro degradability and cytocompatibility were investigated. Results indicated that Sr²⁺ was successfully incorporated into MSN with the collapse of the ordered mesoporous structure. Sr-doping significantly improved the specific surface area, in vitro degradability and cytocompatibility of MSN in a Sr-content-dependent manner. Particularly, excessive Sr-doping gave rise to generating impure strontium silicate which converted into disordered amorphous silica during degradation and hindered the biodegradable behaviors of MSN. Hence, the synthetic Sr-MSNs with excellent surface nature, biodegradability and biocompatibility were supposed to be applied as potential carriers for the controllable release of drugs and ions in numerous clinical applications.     

功能化介孔二氧化硅纳米粒子在药物递送系统中的研究进展

综述了刺激响应型的介孔二氧化硅纳米粒子在药物递送系统中的研究进展,包括氧化还原型释药、磁响应型释药、温度响应型释药、pH响应型释药、酶响应型释药和联合刺激响应型释药,并对未来的发展方向进行了展望,以期为介孔二氧化硅粒子的功能化修饰以及实际应用提供参考。     

功能化介孔二氧化硅纳米粒子在药物递送系统中的研究进展

综述了刺激响应型的介孔二氧化硅纳米粒子在药物递送系统中的研究进展,包括氧化还原型释药、磁响应型释药、温度响应型释药、pH响应型释药、酶响应型释药和联合刺激响应型释药,并对未来的发展方向进行了展望,以期为介孔二氧化硅粒子的功能化修饰以及实际应用提供参考。     

Polymer nanocomposite powders and melt spun fibers filled with silica nanoparticles

Nanocomposite powders from polypropylene filled with surface modified and unmodified fumed silica have been prepared from polymer solution to achieve improved mixing and have been forwarded to fiber melt spinning. The surface of the fumed silica was modified with dodecyl alkoxy silanes. Crystallization velocity and viscosity of the PP nanocomposites thereof were determined to ensure good melt spinning processing conditions for all composite compositions. Upon addition of untreated filler particles, a shear thinning and an increased crystallization velocity of the polymer melt was found, while only minor changes were detected in the presence of surface modified fumed silica particles. The composites and the polymer fibers made from these powder composites by melt spinning were mainly characterized by optical microscopy (OM), scanning electron microscopy (SEM), mechanical measurements, differential scanning calorimetry (DSC), and solid‐state NMR. The unmodified fumed silica was found to have a strong influence on the mechanical fiber properties, while the surface modified silica only a small one. Fibers were additionally characterized with respect to the uniformity, the PP crystallinity, moisture absorption, and the water contact angle. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 218–227, 2007     

Growth and branching of gold nanoparticles through mesoporous silica thin films

Composite materials made of mesoporous oxide thin films containing metallic nanoparticles are of high interest in various fields, including catalysis, biosensing and non-linear optics. We demonstrate in this work the fabrication of such composite materials containing a sub-monolayer of gold nanoparticles (GNPs) of various shapes covered with mesoporous silica thin films. Additionally, the shape of the GNPs (and thus their optical properties) can be modified in situ through seeded growth and branching. Such growth proceeds upon wetting with HAuCl(4) solution, a surfactant (cetyltrimethylammonium bromide, CTAB) and a mild reducing agent (ascorbic acid, AA). The effect of varying several reaction parameters (time and CTAB and AA concentrations) was evaluated, showing that more anisotropic particles are obtained at longer reaction times, lower CTAB concentration and higher AA concentration. The final shape of the GNPs was also found to depend on their initial shape and size, as well as the pore size of the mesoporous film covering them. Because the growth proceeds through the pores of the film, it may lead to shapes that are not easily obtained in solution, such as particles with branches on one side only. Finally, we have confirmed that no damage was induced to the mesoporous silica structure during the growth process and thus the final particles remain well covered by the thin film, which can eventually be used as a filter between the GNPs and the outer medium.