Cytotoxicity and Cellular Uptake of Amorphous Silica Nanoparticles in Human Cancer Cells

The cytotoxic effects of silica nanoparticles (SNPs) on different human cancer cells, as well as the uptake kinetics and pathways of SNPs have been studied here. SNPs with the diameter of ≈20 nm induced a dose‐dependent cytotoxicity in both gastric cancer cells (MGC80–3) and cervical adenocarcinoma epithelial cells (HeLa), but MGC80–3 cells were more susceptible to the cytotoxic effect induced by SNPs. Changes in the nuclear morphology and flow cytometric analysis with annexin V/PI double staining show that SNPs induced a higher degree of apoptosis in MGC80–3 cells. Accordingly, more remarkable reactive oxygen species (ROS) burst is detected in SNP‐treated MGC80–3 cells. Using fluorescein isothiocyanate (FITC)‐labeled SNPs and flow cytometry, it is found that the uptake of SNPs is more efficient in MGC80–3 than in HeLa cells. SNPs are internalized into both cancer cells through energy‐dependent pathway. Inhibitor studies with dynasore and methyl‐β‐cyclodextrin show that these cancer cells took up 20 nm SNPs mainly through the caveolin‐mediated endocytosis, while in HeLa cells SNPs internalization was also via dynamin‐dependent clathrin‐mediated pathway. These findings indicate that SNPs cause differential cytotoxic effects in different human cancer cells, which might be related to the uptake process and efficiency toward these cancer cells.     

Doxorubicin‐Anchored Curcumin Nanoparticles for Multimode Cancer Treatment against Human Liver Carcinoma Cells

Curcumin (Curcuma longa L), a yellow‐colored Indian spice, receives immense attention for the prevention and treatment of various cancers. Despite the superlative therapeutic efficacy, its poor solubility and instability in the aqueous medium hinder the effectiveness of cancer treatment. The novel preparation of curcumin nanoparticles by mechanical grinding of curcumin crystals without any toxic organic solvents is described here for the first time. The surface of curcumin nanoparticles is modified with the negatively charged polyelectrolyte poly(sodium 4‐strynesulfonate) through hydrogen bonding, which is the key to increasing the solubility and stability in the aqueous medium. The negative surface charge is exploited to conjugate doxorubicin drug molecule on the surface of curcumin nanoparticles as evidenced by fluorescence quenching experiments. Doxorubicin‐conjugated curcumin nanoparticles have a higher solubility with an enhanced cytotoxic effect toward the human hepatocellular carcinoma cell line by a reactive‐oxygen‐species‐mediated p53‐dependent apoptotic pathway. The combination of chemotherapy and photodynamic therapy significantly enhances antitumor activity of doxorubicin‐conjugated curcumin nanoparticles, and is expected to be a promising anticancer agent with special reference to human liver carcinoma cells.     

The Internalization,Distribution, and Ultrastructure Damage of Silica Nanoparticles in Human Hepatic L‐02 Cells

Nowadays, due to the wide use of amorphous silica nanoparticles (SiNPs), their adverse effects on human beings are attracting more attention. Understanding the interaction between SiNPs and cells is a fundamental step for toxicity assessment. Therefore, the current study is aimed at elaborating the internalization process, subcellular distribution, ultrastructure damage, and cytotoxicity of two different sizes of SiNPs (Nano‐Si64 and Nano‐Si46) in L‐02 cells. The results indicate that the smaller‐sized SiNPs, Nano‐Si46, accumulate in cells more efficiently and produce a stronger cytotoxic effect than Nano‐Si64. Both types of nanoparticles can accumulate in L‐02 cells through the active endocytotic pathway and passive diffusion, and distribute within endocytotic vesicles or freely in cytoplasma and organelles. Microvillus fracture, membrane injury, mitochondria damage, degranulation of the rough endoplasmic reticulum, lamellar‐like structure, lysosome destruction, autophagosomes, and autophagy‐lysosomes are found in L‐02 cells. Oxidative damage and direct interaction between SiNPs and subcellular structure are responsible for the toxicity.     

A Correlative Analysis of Gold Nanoparticles Internalized by A549 Cells

Fluorescently labeled nanoparticles are widely used to investigate nanoparticle cell interactions by fluorescence microscopy. Owing to limited lateral and axial resolution, nanostructures (<100 nm) cannot be resolved by conventional light micro­scopy techniques. Especially after uptake into cells, a common fate of the fluorescence label and the particle core cannot be taken for granted. In this study, a correlative approach is presented to image fluorescently labeled gold nanoparticles inside whole cells by correlative light and electron microscopy (CLEM). This approach allows for detection of the fluorescently labeled particle shell as well as for the gold core in one sample. In this setup, A549 cells are exposed to 8 nm Atto 647N‐labeled gold nanoparticles (3.3 × 10⁹ particles mL^?1, 0.02 μg Au mL^?1) for 5 h and are subsequently imaged by confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). Eight fluorescence signals located at different intracellular positions are further analyzed by TEM. Five of the eight fluorescence spots are correlated with isolated or agglomerated gold nanoparticles. Three fluorescence signals could not be related to the presence of gold, indicating a loss of the particle shell.     

SiO2包覆共轭聚合物CN-PPV纳米探针的制备与荧光性质

采用纳米沉淀法制备了半导体聚合物CN-PPV纳米粒子,并用改进的Stber方法对纳米粒子进行包覆,获得了发光稳定的SiO2/CN-PPV纳米粒子。用动态光散射(DLS)及透射电镜(TEM)方法对粒子尺寸进行了表征,结果表明包覆前的CN-PPV纳米粒子平均粒径约为30 nm,包覆获得SiO2/CN-PPV纳米粒子的平均粒径约为60 nm。通过紫外-可见吸收光谱及荧光光谱对包覆前后纳米粒子的发光性质进行了比较,发现共轭聚合物CN-PPV包覆后的发射光谱与包覆前相比发生了小的蓝移,表明共轭聚合物的分子构型可能发生了微小变化。SiO2包覆可以提高聚合物发光分子的光稳定性,并且提供用于生物分子耦联的表面,这类材料有望在生物医学成像中获得应用。     

Engineering the Internal Structure of Magnetic Silica Nanoparticles by Thermal Control

Calcination of hydrated iron salts in the pores of both spherical and rod‐shaped mesoporous silica nanoparticles (NPs) changes the internal structure from an ordered 2D hexagonal structure into a smaller number of large voids in the particles with sizes ranging from large hollow cores down to ten nanometer voids. The voids only form when the heating rate is rapid at a rate of 30 °C min^?1. The sizes of the voids are controlled reproducibly by the final calcination temperature; as the temperature is decreased the number of voids decreases as their size increases. The phase of the iron oxide NPs is α‐Fe₂O₃ when annealed at 500 °C, and Fe₃O₄ when annealed at lower temperatures. The water molecules in the hydrated iron (III) chloride precursor salts appear to play important roles by hydrolyzing Si? O? Si bonding, and the resulting silanol is mobile enough to affect the reconstruction into the framed hollow structures at high temperature. Along with hexahydrates, trivalent Fe³⁺ ions are assumed to contribute to the structure disruption of mesoporous silica by replacing tetrahedral Si⁴⁺ ions and making Fe? O? Si bonding. Volume fraction tomography images generated from transmission electron microscopy (TEM) images enable precise visualization of the structures. These results provide a controllable method of engineering the internal shapes in silica matrices containing superparamagnetic NPs.     

Preparation and Fluoroimmunoassay Application of New Red-Region Fluorescent Silica Nanoparticles

This is the first report on the preparation and utilization of a novel red-region fluorescent dye (tetracarboxy aluminum phthalocyanine) doped silica nanoparticles. In these nanoparticles, the tetracarboxy aluminum phthalocyanine molecules were covalently bound to silica matrix to protect the dye leaking from nanoparticles in bio-applications. The surface of the nanoparticles was modified by amino groups and easily bioconjugated with goat anti-human IgG antibody. By employing these nanoparticles as fluorescent probe, a sensitive fluoroimmunoassay method has been developed for the determination of trace level of human IgG. The calibration graph for human IgG was linear over the range of 0–500 ng mL⁻¹ with a detection limit of 1.6 ng mL⁻¹. Compared with the corresponding system using free AlC₄Pc as a probe for determining human IgG, the sensitivity of the proposed system was notably increased. The method was applied to the analysis of human IgG in human sera with satisfactory results.     

Irreversible Adsorption of Serum Proteins onto Nanoparticles

When a material comes in contact with serum or plasma, proteins will immediately adsorb to its surface. The extent of serum protein adsorption as well as the composition of the protein corona is thought to be decisive for the biological fate. The understanding of the mechanism underlying the concurrent adsorption of multiple proteins and the exact ways by which the adsorbed proteins interact with the biological setting, is still rudimentary. For both cases, a correct estimate of the composition of the protein corona is the key for an improved understanding. The protein corona composition is typically analyzed indirectly through analysis of the supernatant after protein desorption. However, in most cases the particles are not analyzed afterward in order to ensure that all proteins indeed have desorbed. Here, the results related to the analysis of the amounts of proteins in the corona are reported, focusing on the desorbed as well as the fraction of proteins that do not desorb. Irreversible protein adsorption can be observed in some cases. The results show that, in addition of the analysis of the supernatant, analysis of the particles is of critical importance to fully characterize the protein corona formed on nanoparticles.     

Glutathione‐Mediated Degradation of Surface‐Capped MnO2 for Drug Release from Mesoporous Silica Nanoparticles to Cancer Cells

Owing to its higher concentration in cancer cells than that in the corresponding normal cells, glutathione (GSH) provides an effective and flexible mechanism to design drug delivery systems. Here a novel GSH‐responsive mesoporous silica nanoparticle (MSN) is reported for controlled drug release. In this system, manganese dioxide (MnO₂) nanostructure, formed by the reduction of KMnO₄ on the surface of carboxyl‐functionalized MSN can block the pores (MSN@MnO₂). By a redox reaction, the capped MnO₂ nanostructure can dissociate into Mn²⁺ in the presence of GSH molecules. The blocked pores are then uncapped, which result in the release of the entrapped drugs. As a proof‐of‐concept, doxorubicin (DOX) as model drug is loaded into MSN@MnO₂. DOX‐loaded MSN@MnO₂ shows an obvious drug release in 10 × 10^?3 m GSH, while no release is observed in the absence of GSH. In vitro studies using human hepatocellular liver carcinoma cell line (HepG2) prove that the DOX‐loaded MSN@MnO₂ can entry into HepG2 cells and efficiently release the loaded DOX, leading to higher cytotoxicity than to that of human normal liver cells (L02). It is believed that further developments of this GSH‐responsive drug delivery system will lead to a new generation of nanodevices for intracellular controlled delivery.     

聚电解质包覆的铕(Ⅲ)配合物@SiO2荧光纳米粒的合成与性质

以二苯甲酰甲烷(DBM)、邻菲罗琳(phen)和丙烯酸(AA)为配体,制备了铕的配合物Eu(Ⅲ)(DBM)2-(phen)(AA).利用St(o)ber法合成了SiO2纳米粒.通过超声辅助,将脂溶性的强荧光铕配合物吸附到SiO2纳米粒上,再包覆阳离子聚电解质聚二烯丙基二甲基氯化铵(PDAC)和阴离子聚电解质聚丙烯酸(P...     

Optical Properties of Ag and Au Nanoparticles Dispersed within the Pores of Monolithic Mesoporous Silica

The optical absorption of silver and gold nanoparticles dispersed within the pores of monolithic mesoporous silica upon annealing at elevated temperatures has been investigated. With decreasing particle size, the surface plasmon resonance position of the particles blue-shifts first and then red-shifts for silver/silica samples, but only red-shifts for gold/silica samples. This size evolution of the resonance position is completely different from that previously reported for fully embedded particles. We assume a local porosity at the particle/matrix interface, such that free surface of particles within the pores may be in contact with ambient air, and present a two-layer core/shell model to calculate the optical properties. These calculations also consider deviations from the optical constants of bulk matter to account for corresponding effects below about 10 nm particle size. From the good agreement between experimental results and model calculations, we conclude a peculiar particle/ambience interaction dominating the size evolution of the resonance. Because of the difference of core electron structure, the relative importance of the effects of local porosity and free surface, respectively, are different for silver and gold. For silver, the effect of the local porosity is stronger, but for gold the opposite is found.     

Multidisciplinary Role of Mesoporous Silica Nanoparticles in Brain Regeneration and Cancers: From Crossing the Blood–Brain Barrier to Treatment

Mesoporous silica nanoparticles (MSNs) have gained wide attention for their role in biomedicine and as drug delivery vehicles. Their structural tunability, high surface area, and easy functionalization impart significant advantages over conventional materials. In this Review, recent advances in the synthesis, drug delivery, and therapeutic roles of MSNs in the treatment of various neurodegenerative and neuroinflammatory diseases are presented. The intention is to understand how MSN formulations that are capable of encapsulating drug molecules can enhance drug delivery by overcoming the blood–brain barrier (BBB) mediated by specific transport processes. The composition and characteristics of the BBB, and how alterations are observed in neurodegenerative diseases including Alzheimer's, epilepsy, and intracerebral hemorrhage are reviewed. Finally, the factors affecting efficient delivery of MSNs into the brain are summarized, and their most promising functional outcomes are discussed.     

Preparation of Mitochondria- and Epigenetics-Targeting Nanoparticles for Suppression of Cancer Metastasis

Epithelial-to-mesenchymal transition (EMT) of carcinoma cells is a promising target for cancer therapy since it is closely related to tumor metastasis and therapeutic resistance. The process of EMT is strongly associated with epigenetic alterations in cancer cells. In addition, recent accumulating evidence suggests that EMT also has a significant influence on inducing cancer stem cells (CSCs). In this study, novel polymer core–lipid shell nanoparticles (PLNPs) are prepared to suppress cancer EMT by the combined effects of the antioxidant activity of core-encapsulated Mn imidazolium porphyrin (MnImP) and the epigenetic control by histone acetyltransferase-encoding plasmid DNA (pHAT) hybridized onto the shell surface. PLNPs show the ability to control the expression of EMT-related markers, resulting in the suppression of EMT in lung epithelial cancer cells (paraquat-treated A549 cells). Furthermore, PLNPs suppress the levels of intracellular mitochondrial ROS and the transformation to CSCs. The results of this study may provide a novel therapeutic strategy against tumor metastasis and treatment resistance.     

Coassembled Nanoparticles Composed of Functionalized Mesoporous Silica and Pillar[5]arene-Appended Gold Nanoparticles as Mitochondrial-Selective Dual-Drug Carriers

Coassembled nanoparticles composed of functionalized mesoporous silica and pillar[5]arene-appended Au nanoparticles obtained through the formation of a host–guest complex are designed and synthesized as a mitochondrial-selective dual-drug delivery system. A pyridinium-based ligand and fluorescein isothiocyanate are immobilized onto mesoporous silica to act as the mitochondria-targeting ligand and fluorescence tracker, respectively, of a material dubbed NP-3. Carboxylated pillar[5]arene-capped Au nanoparticles (CP-AuNPs) are fabricated by the templated reduction of Au³⁺. Interestingly, coassembled nanoparticles (NP-1) composed of doxorubicin (DOX) loaded NP-3 and CP-AuNPs are then prepared via the formation of a host–guest complex between the pyridinium-based ligand of NP-3 and the pillar[5]arene of CP-AuNPs. To demonstrate the effectiveness of NP-2 and NP-1 as mitochondrial targeting drug delivery systems, DOX and F16 are employed as model drugs. These drugs loaded onto NP-2 and CP-AuNPs, respectively, are selectively delivered to mitochondria, indicating the usefulness of NP-2 and CP-AuNPs as mitochondrial-specific drug-delivery carriers in cancer cells. More interestingly, the use of NP-1 is also associated with the selective accumulation of DOX and F16 in mitochondria. The selective mitochondrial-targeting of NP-1 is possible by NP-2 and F16 exposed to the cytoplasm, allowing the codelivery of the two drugs to the mitochondria.