Biodegradable Polysilsesquioxane Nanoparticles as Efficient Contrast Agents for Magnetic Resonance Imaging

Polysilsesquioxane (PSQ) nanoparticles are crosslinked homopolymers formed by condensation of functionalized trialkoxysilanes, and provide an interesting platform for developing biologically and biomedically relevant nanomaterials. In this work, the design and synthesis of biodegradable PSQ particles with extremely high payloads of paramagnetic Gd(III) centers is explored, for use as efficient contrast agents for magnetic resonance imaging (MRI). Two new bis(trialkoxysilyl) derivatives of Gd(III) diethylenetriamine pentaacetate (Gd-DTPA) containing disulfide linkages are synthesized and used to form biodegradable Gd-PSQ particles by base-catalyzed condensation reactions in reverse microemulsions. The Gd-PSQ particles, PSQ-1 and PSQ-2, carry 53.8 wt% and 49.3 wt% of Gd-DTPA derivatives, respectively. In addition, the surface carboxy groups on the PSQ-2 particles can be modified with polyethylene glycol (PEG) and the anisamide (AA) ligand to enhance biocompatibility and cell uptake, respectively. The Gd-PSQ particles are readily degradable to release the constituent Gd(III) chelates in the presence of endogenous reducing agents such as cysteine and glutathione. The MR relaxivities of the Gd-PSQ particles are determined using a 3T MR scanner, with r1 values ranging from 5.9 to 17.8 mMs−1 on a per-Gd basis. Finally, the high sensitivity of the Gd-PSQ particles as T1-weighted MR contrast agents is demonstrated with in vitro MR imaging of human lung and pancreatic cancer cells. The enhanced efficiency of the anisamide-functionalized PSQ-2 particles as a contrast agent is corroborated by both confocal laser scanning microscopy imaging and ICP-MS analysis of Gd content in vitro

Interaction of Mesoporous Silica Nanoparticles with Human Red Blood Cell Membranes: Size and Surface Effects

The interactions of mesoporous silica nanoparticles (MSNs) of different particle sizes and surface properties with human red blood cell (RBC) membranes were investigated by membrane filtration, flow cytometry, and various microscopic techniques. Small MCM-41-type MSNs (∼100 nm) were found to adsorb to the surface of RBCs without disturbing the membrane or morphology. In contrast, adsorption of large SBA-15-type MSNs (∼600 nm) to RBCs induced a strong local membrane deformation leading to spiculation of RBCs, internalization of the particles, and eventual hemolysis. In addition, the relationship between the degree of MSN surface functionalization and the degree of its interaction with RBC, as well as the effect of RBC−MSN interaction on cellular deformability, were investigated. The results presented here provide a better understanding of the mechanisms of RBC−MSN interaction and the hemolytic activity of MSNs and will assist in the rational design of hemocompatible MSNs for intravenous drug delivery and in vivo imaging

Bioresponsive Mesoporous Silica Nanoparticles for Triggered Drug Release

Mesoporous silica nanoparticles (MSNPs) have garnered a great deal of attention as potential carriers for therapeutic payloads. However, achieving triggered drug release from MSNPs in vivo has been challenging. Here, we describe the synthesis of stimulus-responsive polymer-coated MSNPs and the loading of therapeutics into both the core and shell domains. We characterize MSNP drug-eluting properties in vitro and demonstrate that the polymer-coated MSNPs release doxorubicin in response to proteases present at a tumor site in vivo, resulting in cellular apoptosis. These results demonstrate the utility of polymer-coated nanoparticles in specifically delivering an antitumor payload.National Science Foundation (U.S.) (grant R01-CA124427)National Science Foundation (U.S.) (grant U54-CA119349)National Science Foundation (U.S.) (grant U54-CA119335

Zeolite structures loading with an anticancer compound as drug delivery systems

The authors are thankful to Dr. A. S. Azevedo for collecting the powder diffraction data.Two different structures of zeolites, faujasite (FAU) and Linde type A (LTA), were studied to investigate their suitability for drug delivery systems (DDS). The zeolites in the sodium form (NaY and NaA) were used as hosts for encapsulation of α-cyano-4- hydroxycinnamic acid (CHC). CHC, an experimental anticancer drug, was encapsulated in both zeolites by diffusion in liquid phase. These new drug delivery systems, CHC@zeolite, were characterized by spectroscopic techniques (FTIR, 1H NMR, 13C and 27Al solidstate MAS NMR, and UV−vis), chemical analysis, powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). The effect of the zeolites and CHC@zeolite drug deliveries on HCT-15 human colon carcinoma cell line viability was evaluated. Both zeolites alone revealed no toxicity to HCT-15 cancer cells. Importantly, CHC@zeolite exhibit an inhibition of cell viability up to 585-fold, when compared to the non-encapsulated drug. These results indicate the potential of the zeolites for drug loading and delivery into cancer cells to induce cell deathO.M. and R.A. are recipients of fellowships (SFRH/BD/36463/2007, SFRH/BI/51118/2010) from Fundação para a Ciência e a Tecnologia (FCT, Portugal). This work was supported by the FCT projects refs PEst-C/ QUI/UI0686/2011, PEst-C/CTM/LA0011/2011, and PTDC/ SAU-FCF/104347/2008, under the scope of “Programa Operacional Temático Factores de Competitividade” (COMPETE) of “Quadro Comunitário de Apoio III” and cofinanced by Fundo Comunitário Europeu FEDER, and the Centre of Chemistry and Life and Health Sciences Research Institute (University of Minho, Portugal)

Delivery modulation in silica mesoporous supports via alkyl chain pore outlet decoration

This article focuses on the study of the release rate in a family of modified silica mesoporous supports. A collection of solids containing ethyl, butyl, hexyl, octyl, decyl, octadecyl, docosyl, and triacontyl groups anchored on the pore outlets of mesoporous MCM-41 has been prepared and characterized. Controlled release from pore voids has been studied through the delivery of the dye complex tris(2,2¿-bipyridyl)ruthenium(II). Delivery rates were found to be dependent on the alkyl chain length anchored on the pore outlets of the mesoporous scaffolding. Moreover, release rates follow a Higuchi diffusion model, and Higuchi constants for the different hybrid solids have been calculated. A decrease of the Higuchi constants was observed as the alkyl chain used to tune the release profile is longer, confirming the effect that the different alkyl chains anchored into the pore mouths exerted on the delivery of the cargo. Furthermore, to better understand the relation between pore outlets decoration and release rate, studies using molecular dynamics simulations employing force-field methods have been carried out. A good agreement between the calculations and the experimental observations was observed.Financial support from the Spanish Government (projects MAT2009-14564-C04-01 and MAT2009-14564-C04-04) and the Generalitat Valencia (project PROMETEO/2009/016) is gratefully acknowledged.Aznar Gimeno, E.; Sancenón Galarza, F.; Marcos Martínez, MD.; Martínez Mañez, R.; Stroeve, P.; Cano, J.; Amoros Del Toro, P. (2012). Delivery modulation in silica mesoporous supports via alkyl chain pore outlet decoration. Langmuir. 28:2986-2996. https://doi.org/10.1021/la204438jS298629962

Mesoporous silica nanoparticles with tunable pore size for tailored gold nanoparticles

The aim of this paper was to verify a possible correlation between the pore-size of meso- porous silica nanoparticles (MSNs) and the sizes of gold nanoparticles (AuNPs) obtained by an impreg- nation of gold(III) chloride hydrate solution in the MSNs, followed by a specific thermal treatment. Mesoporous silica nanoparticles with tunable pore diameter were synthesized via a surfactant-assisted method. Tetraethoxysilane as silica precursor, cetyl- trimethylammonium bromide (CTAB) as surfactant and toluene as swelling agent were used. By varying the CTAB–toluene molar ratio, the average dimension of the pores could be tuned from 2.8 to 5.5 nm. Successively, thiol groups were grafted on the surface of the MSNs. Finally, the thermal evolution of the gold salt, followed by ‘‘in situ’’ X-ray powder diffraction (XRPD) and thermogravimetric analysis (TGA), revealed an evident correlation among the degradation of the thiol groups, the pore dimension of the MSNs and the size of the AuNPs. The samples were characterized by means of nitrogen adsorption– desorption, transmission electron microscopy, small- angle X-ray scattering, XRPD ‘‘in situ’’ by synchro- tron radiation, and ‘‘ex situ’’ by conventional tech- niques, diffuse reflectance infrared Fourier transform spectroscopy, and TGA

Influence of Cationic meso-Substituted Porphyrins on the Antimicrobial Photodynamic Efficacy and Cell Membrane Interaction in Escherichia coli

Photodynamic inactivation (PDI) is a non-antibiotic option for the treatment of infectious diseases. Although Gram-positive bacteria have been shown to be highly susceptible to PDI, the inactivation of Gram-negative bacteria has been more challenging due to the impermeability properties of the outer membrane. In the present study, a series of photosensitizers which contain one to four positive charges (1–4) were used to evaluate the charge influence on the PDI of a Gram-negative bacteria, Escherichia coli (E. coli), and their interaction with the cell membrane. The dose-response PDI results confirm the relevance of the number of positive charges on the porphyrin molecule in the PDI of E. coli. The difference between the Hill coefficients of cationic porphyrins with 1–3 positive charges and the tetra-cationic porphyrin (4) revealed potential variations in their mechanism of inactivation. Fluorescent live-cell microscopy studies showed that cationic porphyrins with 1–3 positive charges bind to the cell membrane of E. coli, but are not internalized. On the contrary, the tetra-cationic porphyrin (4) permeates through the membrane of the cells. The contrast in the interaction of cationic porphyrins with E. coli confirmed that they followed different mechanisms of inactivation. This work helps to have a better understanding of the structure-activity relationship in the efficiency of the PDI process of cationic porphyrins against Gram-negative bacteria