Xinglu Huang

The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function

The interaction between nanoparticles (NPs) and cells has been studied extensively, but the effect of particle shape on cell behavior has received little attention. Herein three different shaped monodisperse mesoporous silica nanoparticles (MSNs) of similar particle diameter, chemical composition and surface charge but with different aspect ratios (ARs, 1, 2, 4) were specially designed. Then the effects of particle shape of these three different shaped particles on cellular uptake and behavior were studied. The results indicated that these different shaped particles were readily internalized in A375 human melanoma (A375) cells by nonspecific cellular uptake. Particles with larger ARs were taken up in larger amounts and had faster internalization rates. Likewise, it was also found that particles with larger ARs had a greater impact on different aspects of cellular function including cell proliferation, apoptosis, cytoskeleton formation, adhesion and migration. These results show that nanoparticles should no longer be viewed as simple carriers for biomedical applications, but can also play an active role in mediating biological effects. Therefore, our findings may provide useful information for the development of new strategies for the design of efficient drug delivery nanocarriers and therapeutic systems and provide insights into nanotoxicity.

The promotion of human malignant melanoma growth by mesoporous silica nanoparticles through decreased reactive oxygen species

The concept that mesoporous silica nanoparticles (MSNs) are regarded as ideal novel drug delivery carriers in tumor therapy has been introduced extensively, but the effects of MSNs on tumor growth have received little attention. Here a model of nude mice xenografted with human malignant melanoma cells (A375) was used to investigate the effect of MSNs on tumor growth. Surprisingly, we found that MSNs have no toxicity to human malignant melanoma but increasing tumor growth in vivo. It was also confirmed that MSNs significantly promoted A375 cell proliferation and accelerated cell cycle progression in vitro. Cellular uptake mechanism showed that MSNs may affect molecular behavior of A375 cells when they entered into cytoplasm. Then, a detailed mechanism indicated that the promotion effect induced by MSNs was due to the decreasing of endogenous reactive oxygen species (ROS) in cells. Further results demonstrated that the upregulation of anti-apoptotic molecules Bcl-2 expression and the inhibition of NF-kappaB activation by MSNs may promote cell proliferation in a redox-sensitive signal pathway. These results show that tumor growth can be regulated by nanocarriers themselves in a ROS-dependent manner and imply that nanocarriers are not necessarily suitable for all kinds of tumor therapy in development drug delivery system.

Doxorubicin loaded silica nanorattles actively seek tumors with improved anti-tumor effects

Silica nanorattles (SNs) have proven to be promising vehicles for drug delivery. In order to further enhance efficacy and minimize adverse effects, active targeted delivery to tumors is necessary. In this work, SNs modified with a tumor specific targeting ligand, folic acid (FA), was used as carrier of doxorubicin (DOX) (DOX-FA-SNs). Drug loading, cytotoxicity and cellular uptake of DOX-FA-SNs in vitro in human cervical carcinoma cells (HeLa cells) were evaluated. DOX-FA-SNs showed a higher cytotoxicity in human cervical carcinoma cells (HeLa cells) than DOX loaded carboxyl (-COOH) and poly(ethylene glycol) (PEG) modified SNs (DOX-COOH-SNs and DOX-PEG-SNs, respectively). However, DOX-FA-SNs showed lower cytotoxicity in folate receptor negative normal mouse fibroblast cells (L929 cells) compared with free DOX. In vivo tumor-targeted fluorescence imaging indicated specific tumor targeting and uptake of FA-SNs in nude mice bearing subcutaneous HeLa cell-derived xenograft tumors. In vivo anti-tumor experiments demonstrated that DOX-FA-SNs (10 mg kg(-1) of DOX) significantly regressed the tumor growth and reduced toxicity compared with free DOX. These results have great significance in developing and optimizing SNs as effective intracellular delivery and specific tumor targeting vehicles.

General Strategy for Designing Functionalized Magnetic Microspheres for Different Bioapplications

Surface functionalization and water solubility of magnetic nanoparticles are crucial for bioapplication. Here, we describe a synthetic approach for direct preparation of a wide range of functionalized and hydrophilic magnetic polymer particles (MPPs) that is both simple and general and involves using different polymers as the source of functional groups. This simple strategy of changing the polymer used in the reaction can give rise to a wide variety of hydrophilic MPPs with a high number of functional groups. For the purpose of bioapplication, we synthesized three types of MPPs with typical functional groups, such as hydroxyl groups (-OH), amino groups (-NH2), and carboxyl groups (-COOH), and further characterized these MPPs by transmission electronic microscopy (TEM), scanning electronic microscopy (SEM), thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), Raman spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The magnetic saturation of the MPPs was also studied and was adequate for most bioapplications. MPPs were shown to have good biocompatibility using cell proliferation and apoptosis assays. Two types of MPPs with different functional groups were used successfully for intracellular imaging and antibody purification. Our results demonstrate that this simple and general synthesis strategy has potential for designing hydrophilic magnetic nanoparticles with multifunctionalities that cater for a range of bioapplications.

Synthesis of Aqueous CdTe/CdS/ZnS Core/shell/shell Quantum Dots by a Chemical Aerosol Flow Method

This work described a continuous method to synthesize CdTe/CdS/ZnS core/shell/shell quantum dots. In an integrated system by flawlessly combining the chemical aerosol flow system working at high temperature (200–300°C) to generate CdTe/CdS intermediate products and an additional heat-up setup at relatively low temperature to overcoat the ZnS shells, the CdTe/CdS/ZnS multishell structures were realized. The as-synthesized CdTe/CdS/ZnS core/shell/shell quantum dots are characterized by photoluminescence spectra, X-ray diffraction (XRD), energy-dispersive X-ray spectra (EDS), transmission electron microscopy (TEM), and high-resolution transmission electron microscopy (HRTEM). Fluorescence and XRD results confirm that the obtained quantum dots have a core/shell/shell structure. It shows the highest quantum yield above 45% when compared to the rhodamine 6G. The core/shell/shell QDs were more stable via the oxidation experiment by H2O2.

Mesoporous magnetic hollow nanoparticles—protein carriers for lysosome escaping and cytosolic delivery

It is important for a controlled release system to determine whether nanoparticles can penetrate cell membranes and deliver protein into the nuclear or cytosolic compartments of cells, and thus function as carriers. Here, we prepared different functionalized mesoporous magnetic hollow nanoparticles (MMHs) and chose bovine serum albumin (BSA) as a model protein to detect the intracellular trafficking of MMHs. The results showed that MMHs modified with amino groups (AMMHs) were efficient in protein loading and that the loading was dependent on the pH, temperature and ionic strength. Furthermore, we found that the AMMHs not only transported BSA into the cells but also released the BSA carried into the nuclear or cytosolic compartments of the cells. In addition, the nanoparticles were biocompatible, and the encapsulation of BSA in AMMHs did not affect their bioactivity. Taken together, AMMHs are excellent carriers for releasing protein into the cytosol and nucleus, and they have the potential to be used in a controlled release system.

Ultrafast synthesis of water-soluble nanocrystals by the chemical aerosol flow method

Water-soluble CdTe nanocrystals are ultrafast synthesized in less than 10 s via the chemical aerosol flow method.