The exocytosis of mesoporous silica nanoparticles (MSNs) from mammalian cells is demonstrated for the first time. The differences in the degree of exocytosis of MSNs between healthy and cancer cells ...are shown to be responsible for the asymmetric transfer of the particles between both cell types. The exocytosis of highly adsorbent magnetic MSNs proves to be useful as a means for harvesting biomolecules from living cells.
The delivery of proteins instead of DNA into plant cells allows for a transient presence of the protein or enzyme that can be useful for biochemical analysis or genome modifications. This may be of ...particular interest for genome editing, because it can avoid DNA (transgene) integration into the genome and generate precisely modified "nontransgenic" plants. In this work, we explore direct protein delivery to plant cells using mesoporous silica nanoparticles (MSNs) as carriers to deliver Cre recombinase protein into maize (Zea mays) cells. Cre protein was loaded inside the pores of gold-plated MSNs, and these particles were delivered by the biolistic method to plant cells harboring loxP sites flanking a selection gene and a reporter gene. Cre protein was released inside the cell, leading to recombination of the loxP sites and elimination of both genes. Visual selection was used to select recombination events from which fertile plants were regenerated. Up to 20% of bombarded embryos produced calli with the recombined loxP sites under our experimental conditions. This direct and reproducible technology offers an alternative for DNA-free genome-editing technologies in which MSNs can be tailored to accommodate the desired enzyme and to reach the desired tissue through the biolistic method.
Abstract A series of mesoporous silica nanoparticles (MSNs) were synthesized using the co-structure directing method. A non-cytotoxic anionic surfactant, undec-1-en-11-yltetra(ethylene glycol) ...phosphate monoester surfactant (PMES), was used as a structure directing agent (SDA) together with aminopropyltrimethoxysilane that functioned as a co-structure directing agent (CSDA). The morphology and mesoporous structure of these materials were tuned by changing the molar ratio of CSDA and SDA. These mesoporous nanomaterials containing PMES inside the pores showed excellent biocompatibility in vitro . The cellular internalization and endosome escape of PMES–MSNs in cervical cancer cells (HeLa) was demonstrated by flow cytometry and confocal microscopy, respectively. The PMES–MSNs were used as drug delivery carriers for resveratrol, a low water solubility drug, by taking advantage of the hydrophobic environment created by the PMES micelle inside the pores. This surfactant-assisted delivery strategy was tested under physiological conditions showing an increase of the drug loading compared to the material without surfactant and steady release of resveratrol. Finally, the therapeutic properties of resveratrol-loaded PMES–MSNs were evaluated in vitro using HeLa and Chinese hamster ovarian cells. We envision that this surfactant-assisted drug delivery method using MSNs as nanovehicles would lead to a new generation of carrier materials for intracellular delivery of a variety of hydrophobic therapeutic agents.
Shining light for drug delivery: The anticancer drug doxorubicin (Dox, red ellipses in the graphic) was adsorbed on nitroveratryl carbamate‐protected aminopropyl‐functionalized mesoporous silica ...nanoparticles (MSNs). Upon exposure to UV light, positively charged propylammonium moieties were formed on the surface, which caused expulsion of positively charged Dox molecules from the surface of the nanoparticles.
A team effort: Mesoporous silica nanosphere (MSN) materials bifunctionalized with a general acid group and a base group in various relative concentrations are described and shown to function as ...cooperative catalytic systems. The turnover numbers observed indicate that the acid groups can activate substrates in cooperation with the base groups to catalyze reactions that involve carbonyl activation (see picture).
A supramolecular assembly for visible light responsive release of cargo molecules is presented. Sulforhodamine 101 was loaded inside the mesopores of mercaptopropyl-functionalized mesoporous silica ...nanoparticles (MP-MSN) and entrapped by mercaptopropyl-coordinated Ru(bpy)(2)(PPh(3))-moieties. Irradiation with visible light triggers the release of capping species and loaded molecules.
An MCM-41 type mesoporous silica nanosphere-based (MSN) controlled-release delivery system has been synthesized and characterized using surface-derivatized cadmium sulfide (CdS) nanocrystals as ...chemically removable caps to encapsulate several pharmaceutical drug molecules and neurotransmitters inside the organically functionalized MSN mesoporous framework. We studied the stimuli-responsive release profiles of vancomycin- and adenosine triphosphate (ATP)-loaded MSN delivery systems by using disulfide bond-reducing molecules, such as dithiothreitol (DTT) and mercaptoethanol (ME), as release triggers. The biocompatibility and delivery efficiency of the MSN system with neuroglial cells (astrocytes) in vitro were demonstrated. In contrast to many current delivery systems, the molecules of interest were encapsulated inside the porous framework of the MSN not by adsorption or sol-gel types of entrapment but by capping the openings of the mesoporous channels with size-defined CdS nanoparticles to physically block the drugs/neurotransmitters of certain sizes from leaching out. We envision that this new MSN system could play a significant role in developing new generations of site-selective, controlled-release delivery nanodevices.
Applying nanotechnology to plant science requires efficient systems for the delivery of nanoparticles (NPs) to plant cells and tissues. The presence of a cell wall in plant cells makes it challenging ...to extend the NP delivery methods available for animal research. In this work, research is presented which establishes an efficient NP delivery system for plant tissues using the biolistic method. It is shown that the biolistic delivery of mesoporous silica nanoparticle (MSN) materials can be improved by increasing the density of MSNs through gold plating. Additionally, a DNA‐coating protocol is used based on calcium chloride and spermidine for MSN and gold nanorods to enhance the NP‐mediated DNA delivery. Furthermore, the drastic improvement of NP delivery is demonstrated when the particles are combined with 0.6 μm gold particles during bombardment. The methodology described provides a system for the efficient delivery of NPs into plant cells using the biolistic method.
Biolistic‐mediated delivery of mesoporous silica nanoparticles (MSNs) and DNA to plant cells is performed via two strategies: gold plating the surfaces of MSNs to increase momentum during bombardment, and co‐bombardment of the MSNs with 0.6 μm gold particles. In both cases, a CaCl2/spermidine‐based protocol is used to coat DNA onto the particles.
Abstract A series of organically functionalized, MCM-41 type mesoporous silica nanoparticle materials (PAP-LP-MSN and AP-PAP-MSN) with different pore sizes (5.7 nm and 2.5 nm, respectively) were ...synthesized and characterized. We selectively decorated the exterior particle surface of PAP-LP-MSN and the interior pore surface of AP-PAP-MSN with an oligonucleotide intercalating phenanthridinium functionality. While phenanthridinium itself is a cell membrane impermeable molecule, we demonstrated that both phenanthridinium-immobilized PAP-LP-MSN and AP-PAP-MSN materials could indeed be internalized by live human cervical cancer cells (HeLa). We discovered that the PAP-LP-MSN nanoparticles with the phenanthridium groups located on the exterior surface were able to bind to cytoplasmic oligonucleotides, such as messenger RNAs, of HeLa cells resulting in severe cell growth inhibition. In contrast, the cytotoxicity of AP-PAP-MSN, where the same oligonucleotide intercalating molecules were anchored inside the pores, was significantly lowered upon the endocytosis by HeLa cells. We envision that this approach of combining the selective functionalization of the two different surfaces (exterior particle and interior pore surfaces) with morphology control of mesoporous silica nanoparticles would lead to a new generation of nanodevices with tunable biocompatibility and cell membrane trafficking properties for many biomedical applications.
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