A Vesicle Supra‐Assembly Approach to Synthesize Amine‐Functionalized Hollow Dendritic Mesoporous Silica Nanospheres for Protein Delivery

Intracellular delivery of proteins is a promising strategy of intervention in disease, which relies heavily on the development of efficient delivery platforms due to the cell membrane impermeability of native proteins, particularly for negatively charged large proteins. This work reports a vesicle supra‐assembly approach to synthesize novel amine‐functionalized hollow dendritic mesoporous silica nanospheres (A‐HDMSN). An amine silica source is introduced into a water–oil reaction solution prior to the addition of conventional silica source tetraethylorthosilicate. This strategy favors the formation of composite vesicles as the building blocks which further assemble into the final product. The obtained A‐HDMSN have a cavity core of ≈170 nm, large dendritic mesopores of 20.7 nm in the shell and high pore volume of 2.67 cm³ g^?1. Compared to the calcined counterpart without amine groups (C‐HDMSN), A‐HDMSN possess enhanced loading capacity to large negative proteins (IgG and β‐galactosidase) and improved cellular uptake performance, contributed by the cationic groups. A‐HDMSN enhance the intracellular uptake of β‐galactosidase by up to 5‐fold and 40‐fold compared to C‐HDMSN and free β‐galactosidase, respectively. The active form of β‐galactosidase delivered by A‐HDMSN retains its intracellular catalytic functions.     

Size‐Dependent Cytotoxicity of Monodisperse Silica Nanoparticles in Human Endothelial Cells

The effect that monodisperse amorphous spherical silica particles of different sizes have on the viability of endothelial cells (EAHY926 cell line) is investigated. The results indicate that exposure to silica nanoparticles causes cytotoxic damage (as indicated by lactate dehydrogenase (LDH) release) and a decrease in cell survival (as determined by the tetrazolium reduction, MTT, assay) in the EAHY926 cell line in a dose‐related manner. Concentrations leading to a 50% reduction in cell viability (TC₅₀) for the smallest particles tested (14‐, 15‐, and 16‐nm diameter) ranging from 33 to 47 µg cm^?2 of cell culture differ significantly from values assessed for the bigger nanoparticles: 89 and 254 µg cm^?2 (diameter of 19 and 60 nm, respectively). Two fine silica particles with diameters of 104 and 335 nm show very low cytotoxic response compared to nanometer‐sized particles with TC₅₀ values of 1095 and 1087 µg cm^?2, respectively. The smaller particles also appear to affect the exposed cells faster with cell death (by necrosis) being observed within just a few hours. The surface area of the tested particles is an important parameter in determining the toxicity of monodisperse amorphous silica nanoparticles.     

Nanoarchitectured Structure and Surface Biofunctionality of Mesoporous Silica Nanoparticles

Mesoporous silica nanoparticles (MSNs), one of the important porous materials, have garnered interest owing to their highly attractive physicochemical features and advantageous morphological attributes. They are of particular importance for use in diverse fields including, but not limited to, adsorption, catalysis, and medicine. Despite their intrinsic stable siliceous frameworks, excellent mechanical strength, and optimal morphological attributes, pristine MSNs suffer from poor drug loading efficiency, as well as compatibility and degradability issues for therapeutic, diagnostic, and tissue engineering purposes. Collectively, the desirable and beneficial properties of MSNs have been harnessed by modifying the surface of the siliceous frameworks through incorporating supramolecular assemblies and various metal species, and through incorporating supramolecular assemblies and various metal species and their conjugates. Substantial advancements of these innovative colloidal inorganic nanocontainers drive researchers in promoting them toward innovative applications like stimuli (light/ultrasound/magnetic)-responsive delivery-associated therapies with exceptional performance in vivo. Here, a brief overview of the fabrication of siliceous frameworks, along with discussions on the significant advances in engineering of MSNs, is provided. The scope of the advancement in terms of structural and physicochemical attributes and their effects on biomedical applications with a particular focus on recent studies is emphasized. Finally, interesting perspectives are recapitulated, along with the scope toward clinical translation.     

Mesoporous Silica Nanoparticles: Synthesis,Biocompatibility and Drug Delivery

In the past decade, mesoporous silica nanoparticles (MSNs) have attracted more and more attention for their potential biomedical applications. With their tailored mesoporous structure and high surface area, MSNs as drug delivery systems (DDSs) show significant advantages over traditional drug nanocarriers. In this review, we overview the recent progress in the synthesis of MSNs for drug delivery applications. First, we provide an overview of synthesis strategies for fabricating ordered MSNs and hollow/rattle‐type MSNs. Then, the in vitro and in vivo biocompatibility and biotranslocation of MSNs are discussed in relation to their chemophysical properties including particle size, surface properties, shape, and structure. The review also highlights the significant achievements in drug delivery using mesoporous silica nanoparticles and their multifunctional counterparts as drug carriers. In particular, the biological barriers for nano‐based targeted cancer therapy and MSN‐based targeting strategies are discussed. We conclude with our personal perspectives on the directions in which future work in this field might be focused.     

The Architecture and Function of Monoclonal Antibody‐Functionalized Mesoporous Silica Nanoparticles Loaded with Mifepristone: Repurposing Abortifacient for Cancer Metastatic Chemoprevention

The circulating tumor cells (CTCs) existing in cancer survivors are considered the root cause of cancer metastasis. To prevent the devastating metastasis cascade from initiation, we hypothesize that a biodegradable nanomaterial loaded with the abortifacient mifepristone (MIF) and conjugated with the epithelial cell adhesion molecule antibody (aEpCAM) may serve as a safe and effective cancer metastatic preventive agent by targeting CTCs and preventing their adhesion‐invasion to vascular intima. It is demonstrated that MIF‐loaded mesoporous silica nanoparticles (MSN) coated with aEpCAM (aE‐MSN‐M) can specifically target and bind colorectal cancer cells in either cell medium or blood through EpCAM recognition proven by quantitative flow cytometric detection and free aEpCAM competitive assay. The specific binding results in downregulation of the captured cells and drives them into G0/G1 phase primarily attributed to the effect of aEpCAM. The functional nanoparticles significantly inhibit the heteroadhesion between cancer cells and endothelial cells, suggesting the combined inhibition effects of aEpCAM and MIF on E‐selectin and ICAM‐1 expression. The functionalized nanoparticles circulate in mouse blood long enough to deliver MIF and inhibit lung metastasis. The present proof‐of‐concept study shows that the aE‐MSN‐M can prevent cancer metastasis by restraining CTC activity and their adhesion‐invasion to vascular intima.     

Bioinspired Diselenide‐Bridged Mesoporous Silica Nanoparticles for Dual‐Responsive Protein Delivery

Controlled delivery of protein therapeutics remains a challenge. Here, the inclusion of diselenide‐bond‐containing organosilica moieties into the framework of silica to fabricate biodegradable mesoporous silica nanoparticles (MSNs) with oxidative and redox dual‐responsiveness is reported. These diselenide‐bridged MSNs can encapsulate cytotoxic RNase A into the 8–10 nm internal pores via electrostatic interaction and release the payload via a matrix‐degradation controlled mechanism upon exposure to oxidative or redox conditions. After surface cloaking with cancer‐cell‐derived membrane fragments, these bioinspired RNase A‐loaded MSNs exhibit homologous targeting and immune‐invasion characteristics inherited from the source cancer cells. The efficient in vitro and in vivo anti‐cancer performance, which includes increased blood circulation time and enhanced tumor accumulation along with low toxicity, suggests that these cell‐membrane‐coated, dual‐responsive degradable MSNs represent a promising platform for the delivery of bio‐macromolecules such as protein and nucleic acid therapeutics.     

Biocompatibility,Biodistribution, and Drug‐Delivery Efficiency of Mesoporous Silica Nanoparticles for Cancer Therapy in Animals

Mesoporous silica nanoparticles (MSNs) are a promising material for drug delivery. In this Full Paper, MSNs are first shown to be well tolerated, as demonstrated by serological, hematological, and histopathological examinations of blood samples and mouse tissues after MSN injection. Biodistribution studies using human cancer xenografts are carried out with in vivo imaging and fluorescent microscopy imaging, as well as with inductively coupled plasma mass spectroscopy. The results show that MSNs preferentially accumulate in tumors. Finally, the drug‐delivery capability of MSNs is demonstrated by following tumor growth in mice treated with camptothecin‐loaded MSNs. These results indicate that MSNs are biocompatible, preferentially accumulate in tumors, and effectively deliver drugs to the tumors and suppress tumor growth.     

Amorphous Silica Nanoparticles Promote Monocyte Adhesion to Human Endothelial Cells: Size‐Dependent Effect

There is evidence that nanoparticles can induce endothelial dysfunction. Here, the effect of monodisperse amorphous silica nanoparticles (SiO₂‐NPs) of different diameters on endothelial cells function is examined. Human endothelial cell line (EA.hy926) or primary human pulmonary artery endothelial cells (hPAEC) are seeded in inserts introduced or not above triple cell co‐cultures (pneumocytes, macrophages, and mast cells). Endothelial cells are incubated with SiO₂‐NPs at non‐cytotoxic concentrations for 12 h. A significant increase (up to 2‐fold) in human monocytes adhesion to endothelial cells is observed for 18 and 54 nm particles. Exposure to SiO₂‐NPs induces protein expression of adhesion molecules (ICAM‐1 and VCAM‐1) as well as significant up‐regulation in mRNA expression of ICAM‐1 in both endothelial cell types. Experiments performed with fluorescent‐labelled monodisperse amorphous SiO₂‐NPs of similar size evidence nanoparticle uptake into the cytoplasm of endothelial cells. It is concluded that exposure of human endothelial cells to amorphous silica nanoparticles enhances their adhesive properties. This process is modified by the size of the nanoparticle and the presence of other co‐cultured cells.     

Multifunctional Mesoporous Silica Nanoparticles with Thermal‐Responsive Gatekeeper for NIR Light‐Triggered Chemo/Photothermal‐Therapy

In this work, a matrix metalloproteinase (MMP)‐triggered tumor targeted mesoporous silica nanoparticle (MSN) is designed to realize near‐infrared (NIR) photothermal‐responsive drug release and combined chemo/photothermal tumor therapy. Indocyanine green (ICG) and doxorubicin (DOX) are both loaded in the MSN modified with thermal‐cleavable gatekeeper (Azo‐CD), which can be decapped by ICG‐generated hyperthermia under NIR illumination. A peptidic sequence containing a short PEG chain, matrix metalloproteinase (MMP) substrate (PLGVR) and tumor cell targeting motif (RGD) are further decorated on the MSN via a host–guest interaction. The PEG chain can protect the MSN during the circulation and be cleaved off in the tumor tissues with overexpressed MMP, and then the RGD motif is switched on to target tumor cells. After the tumor‐triggered targeting process, the NIR irradiation guided by ICG fluorescence can trigger cytosol drug release and realize combined chemo/photothermal therapy.