Magnetic nanoparticles: recent developments in drug delivery system

Nanostructured functional materials have demonstrated their great potentials in medical applications, attracting increasing attention because of the opportunities in cancer therapy and the treatment of other ailments. This article reviews the problems and recent advances in the development of magnetic NPs for drug delivery.     

负载氯喹的骨靶向纳米颗粒打破肿瘤细胞增殖与骨吸收之间的恶性循环

肿瘤细胞增殖与骨吸收之间的恶性循环加剧了骨肿瘤的进展和转移风险.为此,我们设计并制备了聚乙二醇-阿仑膦酸钠修饰的聚多巴胺(PPA)纳米粒子,并在其表面负载自噬抑制剂氯喹(CQ),期望利用该治疗载体(PPA/CQ)打破肿瘤细胞增殖与骨吸收之间的恶性循环,从而有效地治疗骨肿瘤.实验证明,PPA/CQ可以有效地富集到骨组织,...     

Hollow mesoporous silica nanoparticles as nanocarriers employed in cancer therapy: A review

Hollow mesoporous silica nanoparticles (HMSNs) have become an attractive drug carrier because of their unique characteristics including stable physicochemical properties, large specific surface area and facile functionalization, especially made into intelligent drug delivery systems (DDSs) for cancer therapy. HMSNs are employed to transport traditional anti-tumor drugs, which can solve the problems of drugs with instability, poor solubility and lack of recognition, etc., while significantly improving the anti-tumor effect. And an unexpected good result will be obtained by combining functional molecules and metal species with HMSNs for cancer diagnosis and treatment. Actually, HMSNs-based DDSs have developed relatively mature in recent years. This review briefly describes how to successfully prepare an ordinary HMSNs-based DDS, as well as its degradation, different stimuli-responses, targets and combination therapy. These versatile intelligent nanoparticles show great potential in clinical aspects.     

Enhancement of radiation cytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles

Gold nanoparticles (GNPs) and modified GNPs having two kinds of functional molecules, cysteamine (AET) and thioglucose (Glu), are synthesized. Cell uptake and radiation cytotoxicity enhancement in a breast-cancer cell line (MCF-7) versus a nonmalignant breast-cell line (MCF-10A) are studied. Transmission electron microscopy (TEM) results show that cancer cells take up functional Glu-GNPs significantly more than naked GNPs. The TEM results also indicate that AET-capped GNPs are mostly bound to the MCF-7 cell membrane, while Glu-GNPs enter the cells and are distributed in the cytoplasm. After MCF-7 cell uptake of Glu-GNPs, or binding of AET-GNPs, the in vitro cytotoxicity effects are observed at 24, 48, and 72 hours. The results show that these functional GNPs have little or no toxicity to these cells. To validate the enhanced killing effect on cancer cells, various forms of radiation are applied such as 200 kVp X-rays and gamma-rays, to the cells, both with and without functional GNPs. By comparison with irradiation alone, the results show that GNPs significantly enhance cancer killing.     

Targeted delivery of nanoparticles bearing fibroblast growth factor-2 by ultrasonic microbubble destruction for therapeutic arteriogenesis

Therapeutic strategies in which recombinant growth factors are injected to stimulate arteriogenesis in patients suffering from occlusive vascular disease stand to benefit from improved targeting, less invasiveness, better growth-factor stability, and more sustained growth-factor release. A microbubble contrast-agent-based system facilitates nanoparticle deposition in tissues that are targeted by 1-MHz ultrasound. This system can then be used to deliver poly(D,L-lactic-co-glycolic acid) nanoparticles containing fibroblast growth factor-2 to mouse adductor muscles in a model of hind-limb arterial insufficiency. Two weeks after treatment, significant increases in both the caliber and total number of collateral arterioles are observed, indicating that the delivery of nanoparticles bearing fibroblast growth factor-2 by ultrasonic microbubble destruction may represent an effective and minimally invasive strategy for the targeted stimulation of therapeutic arteriogenesis.     

Inhibition of influenza virus infection by multivalent sialic-acid-functionalized gold nanoparticles

An efficient synthesis of sialic-acid-terminated glycerol dendron to chemically functionalize 2 nm and 14 nm gold nanoparticles (AuNPs) is described. These nanoparticles are highly stable and show high activity towards the inhibition of influenza virus infection. As the binding of the viral fusion protein hemagglutinin to the host cell surface is mediated by sialic acid receptors, a multivalent interaction with sialic-acid-functionalized AuNPs is expected to competitively inhibit viral infection. Electron microscopy techniques and biochemical analysis show a high binding affinity of the 14 nm AuNPs to hemagglutinin on the virus surface and, less efficiently, to isolated hemagglutinin. The functionalized AuNPs are nontoxic to the cells under the conditions studied. This approach allows a new type of molecular-imaging activity-correlation and is of particular relevance for further application in alternative antiviral therapy.     

In vitro and in vivo evaluation of puerarin-loaded PEGylated mesoporous silica nanoparticles

Puerarin, which is extracted from Chinese medicine, is widely used in China and mainly used as a therapeutic agent for the treatment of cardiovascular diseases. Owing to its short elimination half-life in human beings, frequently intravenous administration of high doses of puerarin may be needed, which possibly leads to severe and acute side effects. The development of an effective sustained-release drug delivery system is urgently needed. In this study, PEGylated mesoporous silica nanoparticles (PEG-MSNs) had become a preferred way to prolong the half-life and improve the bioavailability of drugs. The release of puerarin from PEG-MSNs was pH dependent, and the release rate was much faster at lower pH than that at higher pH. Moreover, the PEG-MSNs exhibited improved blood compatibility over the MSNs in terms of low hemolysis, and it could also reduce the side effect of hemolysis induced by PUE. Compared with puerarin, PUE-loaded PEG-MSNs showed a 2.3-fold increase in half-life of puerarin and a 1.47-fold increase in bioavailability. Thus, the PEG-MSNs hold the substantial potential to be further developed as an effective sustained-release drug delivery system.     

Characterisation and intrinsic magnetic resonance properties of nickel nanoparticles

Nickel nanoparticles have been extensively characterised by atomic force microscopy (AFM), scanning electron microscopy (SEM) and confocal micro-Raman spectroscopy. AFM underestimates the particle size compared to SEM measurements. It is shown that Raman spectroscopy can detect the nanometre-thick NiO layer on the particles having frequency shifts of the modes indicative of phonon confinement. The magnetic properties of the particles are studied by ferromagnetic resonance (FMR) of magnetic field aligned particles. The alignment is achieved by suspending the particles in the liquid crystal MBBA and freezing the liquid in a 0.4 T DC magnetic field. The in-field solidification locks the direction of maximum magnetisation of the particles parallel to the direction of the applied DC magnetic field. This removes the effects of dynamical particle fluctuations of the nanoparticles on the magnetic properties allowing a study of the intrinsic magnetic properties of the magnetic nanoparticles. The intensity of the FMR signal decreased with lowering temperature for the particles frozen in the liquid in a 0.4 T DC magnetic field. The effect is suggested to be due to a reduction of the microwave skin depth with lowering temperature.     

Optical and surface morphological properties of triethylamine passivated lead sulphide nanoparticles

The triethylamine capped lead sulphide (PbS) nanoparticles were successfully synthesized by simple wet chemical method. The synthesized product has been characterized by powder X-ray diffraction (XRD), UV–vis spectrophotometry, FTIR spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM) and photoluminescence studies. The size of the PbS nanoparticles was determined from AFM, TEM, XRD and from these studies it is found that the size of the particles of the order of 10–15 nm. Significant “blue shift” from bulk material was observed on the PbS nanoparticles using UV–vis and photoluminescence spectrum.     

Multiphoton molecular photorelease in click-chemistry-functionalized gold nanoparticles

Yellow-green controlled photorelease: probes click-linked to peptide-coated gold nanospheres by a triazole ring can be released in living cells under a focused 561 nm laser at low power. Photocleaving follows a three-photon event stimulated by the excitation of the localized surface plasmon resonance.     

Photoresponsive coumarin-stabilized polymeric nanoparticles as a detectable drug carrier

The ability to create aqueous suspended stable nanoparticles of the hydrophobic homopolymer poly(?‐caprolactone) end‐functionalized with coumarin moieties (CPCL) is demonstrated. Nanoparticles of CPCL are prepared in a continuous manner using nanoprecipitation. The resulting nanoparticles are spherical in morphology, about 40 nm in diameter, and possess a narrow size distribution and excellent stability over 4 months by repulsive surface charge. Nanoparticle size can be easily controlled by manipulating the concentration of CPCL in the solution. The interparticle assembly between the nanoparticles can be reversibly adjusted with photoirradiation due to photoinduced [2 + 2] cyclodimerization and cleavage between the coumarin molecules. In addition, the CPCL nanoparticles show significant cellular uptake without cytotoxicity, and the intrinsic fluorescence of the coumarin functional group permits the direct detection of cellular internalization.     

Surface functionalization of nanoparticles to control cell interactions and drug release

Nanoparticles made from poly(dl-lactide-co-glycolide) (PLGA) are used to deliver a wide range of bioactive molecules, due to their biocompatibility and biodegradability. This study investigates the surface modification of PLGA nanoparticles via the layer-by-layer (LbL) deposition of polyelectrolytes, and the effects of these coatings on the release behavior, cytotoxicity, hemolytic activity, and cellular uptake efficiency. PLGA nanoparticles are modified via LbL adsorption of two polyelectrolyte pairs: 1) poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) and 2) poly(L-lysine hydrobromide) (PLL) and dextran sulfate (DES). It is demonstrated that both PAH/PSS and PLL/DES coatings suppress the burst release usually observed for unmodified PLGA nanoparticles and that the release behavior can be adjusted by changing the layer numbers, layer materials, or by crosslinking the layer constituents. Neither bare nor polyelectrolyte-modified PLGA nanoparticles show any signs of cytotoxicity. However, nanoparticles with a positively charged polyelectrolyte as the outermost layer induce hemolysis, whereas uncoated particles or particles with a negatively charged polyelectrolyte as the outermost layer show no hemolytic activity. Furthermore, particles with either PAH or PLL as the outermost layer also demonstrate a higher uptake efficiency by L929 fibroblast cells, due to a higher cell-particle affinity. This study suggests that LbL coating of PLGA nanoparticles can control the release behavior of bioactive molecules as well as the surface activity, therefore providing a promising strategy to enhance the efficiency of nanoparticulate drug-delivery systems.     

Preparation of magnetic mesoporous silica nanoparticles as a multifunctional platform for potential drug delivery and hyperthermia

We report the preparation of magnetic mesoporous silica (MMS) nanoparticles with the potential multifunctionality of drug delivery and magnetic hyperthermia. Carbon-encapsulated magnetic colloidal nanoparticles (MCN@C) were used to coat mesoporous silica shells for the formation of the core-shell structured MMS nanoparticles (MCN@C/mSiO₂), and the rattle-type structured MMS nanoparticles (MCN/mSiO₂) were obtained after the removal of the carbon layers from MCN@C/mSiO₂ nanoparticles. The morphology, structure, magnetic hyperthermia ability, drug release behavior, in vitro cytotoxicity and cellular uptake of MMS nanoparticles were investigated. The results revealed that the MCN@C/mSiO₂ and MCN/mSiO₂ nanoparticles had spherical morphology and average particle sizes of 390 and 320 nm, respectively. The MCN@C/mSiO₂ nanoparticles exhibited higher magnetic hyperthermia ability compared to the MCN/mSiO₂ nanoparticles, but the MCN/mSiO₂ nanoparticles had higher drug loading capacity. Both MCN@C/mSiO₂ and MCN/mSiO₂ nanoparticles had similar drug release behavior with pH-controlled release and temperature-accelerated release. Furthermore, the MCN@C/mSiO₂ and MCN/mSiO₂ nanoparticles showed low cytotoxicity and could be internalized into HeLa cells. Therefore, the MCN@C/mSiO₂ and MCN/mSiO₂ nanoparticles would be promising for the combination of drug delivery and magnetic hyperthermia treatment in cancer therapy.     

Logic-embedded vectors for intracellular partitioning, endosomal escape, and exocytosis of nanoparticles

A new generation of nanocarriers, logic-embedded vectors (LEVs), is endowed with the ability to localize components at multiple intracellular sites, thus creating an opportunity for synergistic control of redundant or dual-hit pathways. LEV encoding elements include size, shape, charge, and surface chemistry. In this study, LEVs consist of porous silicon nanocarriers, programmed for cellular uptake and trafficking along the endosomal pathway, and surface-tailored iron oxide nanoparticles, programmed for endosomal sorting and partitioning of particles into unique cellular locations. In the presence of persistent endosomal localization of silicon nanocarriers, amine-functionalized nanoparticles are sorted into multiple vesicular bodies that form novel membrane-bound compartments compatible with cellular secretion, while chitosan-coated nanoparticles escape from endosomes and enter the cytosol. Encapsulation within the porous silicon matrix protects these nanoparticle surface-tailored properties, and enhances endosomal escape of chitosan-coated nanoparticles. Thus, LEVs provide a mechanism for shielded transport of nanoparticles to the lesion, cellular manipulation at multiple levels, and a means for targeting both within and between cells.     

多糖涂覆的氧化铁纳米粒子的合成及其药物递送应用研究进展

近年来,氧化铁纳米粒子(Iron Oxide Nanoparticles,IONPs)由于具有超顺磁性、生物相容性、比表面积大、易分离等特点而备受科学界关注.然而,裸露的IONPs容易聚集和氧化而失去其应有的特性,采用多糖进行涂覆不仅能提高IONPs的稳定性和生物相容性,还能通过多糖与其他生物活性物质结合,赋予INOPs新的功能.多糖涂覆的IONPs充分结合了多糖的生化特性与磁芯的理化特性,在药物递送中展现出巨大的应用潜力.本文综述了多糖涂覆IONPs的合成方法、合成过程的影响因素、多糖与IONPs的结合机理及其在药物递送中的应用,最后对多糖涂覆的IONPs的合成及其在药物递送方面的应用进行了总结和展望.     

Electrically active, doped monocrystalline silicon nanoparticles produced by hot wire thermal catalytic pyrolysis

Doped silicon nanoparticles have successfully been produced by hot wire thermal catalytic pyrolysis at 40 mbar and a filament temperature of 1800 °C, using a mixture of silane and diborane or phosphine. All particles are monocrystalline with shapes ranging from an octahedron to varying degrees of truncation of this basic shape, with an average diameter of 22 nm. To determine the doping activity, the resistivity of the nanopowders was measured at successive compression levels. While boron doped particles have clean surfaces and are electrically active, with compacted powder having a resistivity of the order of 10³ Ω m, phosphorus doped particles are covered by an oxide layer whose thickness increases from 0.3 nm to 0.6 nm with higher phosphine concentrations. Furthermore, the phosphor atoms are localised at the interface to this surface layer, where they are electrically inactive. These powders have a resistivity in the order of 10⁷ Ω m.     

Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery

We report the development of a biostable methotrexate-immobilized iron oxide nanoparticle drug carrier that may potentially be used for real-time monitoring of drug delivery through magnetic resonance imaging. Methotrexate (MTX) was immobilized on the nanoparticle surface via a poly(ethylene glycol) self-assembled monolayer (PEG SAM). The cytotoxicity of the nanoparticle-drug conjugate (NP-PEG-MTX) to target cells was studied with 9L glioma cells. Cellular uptake experiments showed that the uptake of NP-PEG-MTX conjugates by glioma cells was considerably higher than that of control nanoparticles. Magnetic resonance imaging in 9L cells cultured with NP-PEG-MTX of various concentrations showed significant contrast enhancement. NP-PEG-MTX demonstrated higher cytotoxicity in 9L cells to free MTX in vitro. Leucovorin, an MTX antidote, was used to rescue the cells that had been exposed to NP-PEG-MTX or free MTX, and the experiment verified the biocompatibility of NP-PEG-MTX conjugates and the MTX on NP-PEG-MTX conjugates to be the true source of the cytotoxicity to the target cells. TEM results showed that NP-PEG-MTX conjugates were internalized into the 9L cellular cytoplasm and retained its crystal structure therein for up to 144 h, as identified by electron diffraction. This prolonged particle retention may allow physicians to image tumor cells exposed to the NP-PEG-MTX conjugate over an extended therapeutic time course.     

Fluorescent polymeric nanoparticles: aggregation and phase behavior of pyrene and amphotericin B molecules in nanoparticle cores

The state of aggregation of compounds, especially drugs, in the cores of nanoparticles (NPs) formed by rapid precipitation is a significant unresolved issue. The state can control the dissolution kinetics from the NP, bioavailability, and chemical stability of the compound. A block-copolymer-directed rapid precipitation process is used to form ≈100 nm NPs comprising mixtures of hydrophobic species including fluorescent probe molecules. Fluorescence measurements are used to probe the state of aggregation and dynamics of rearrangement of pyrene (Py), Hostasol Yellow (HosY), and amphotericin B (AmpB) in NP cores. The Flory-Huggins theory of mixing is used to predict the miscibility or phase separation of the fluorophores from the host NP core material (polystyrene, cholesterol, or polycaprolactone). For Py, excimer fluorescence shows an initial microphase separation in the polystyrene core. Over time the Py redistributes more uniformly with a decrease in excimer and increase in monomer fluorescence. The Flory-Huggins theory predicts the miscibility. For HosY, the fluorescence quenching is not time-dependent, thus indicating stability of the microphase-separated fluorophores, which is consistent with the Flory-Huggins theory calculations. For the drug compound AmpB, the amphiphilic character of the molecule creates unusual "anti-Ostwald" ripening behavior in which the size distribution decreases and narrows over time, and the fluorescence demonstrates an increased ordering in the NP core over time--opposite to the behavior observed for Py.