A Biodegradation Study of SBA-15 Microparticles in Simulated Body Fluid and <i>in Vivo</i>

Mesoporous silica has received considerable attention as a drug delivery vehicle because of its large surface area and large pore volume for loading drugs and large biomolecules. Recently, mesoporous silica microparticles have shown potential as a three-dimensional vaccine platform for modulating dendritic cells via spontaneous assembly of microparticles in a specific region after subcutaneous injection. For further <i>in vivo</i> applications, the biodegradation behavior of mesoporous silica microparticles must be studied and known. Until now, most biodegradation studies have focused on mesoporous silica nanoparticles (MSNs); here, we report the biodegradation of hexagonally ordered mesoporous silica, SBA-15, with micrometer-sized lengths (∼32 μm with a high aspect ratio). The degradation of SBA-15 microparticles was investigated in simulated body fluid (SBF) and in mice by analyzing the structural change over time. SBA-15 microparticles were found to degrade in SBF and <i>in vivo</i>. The erosion of SBA-15 under biological conditions led to a loss of the hysteresis loop in the nitrogen adsorption/desorption isotherm and fingerprint peaks in small-angle X-ray scattering, specifically indicating a degradation of ordered mesoporous structure. Via comparison to previous results of degradation of MSNs in SBF, SBA-15 microparticles degraded faster than MCM-41 nanoparticles presumably because SBA-15 microparticles have a pore size (∼8 nm) and a pore volume larger than those of MCM-41 mesoporous silica. The surface functional groups, the residual amounts of organic templates, and the hydrothermal treatment during the synthesis could affect the rate of degradation of SBA-15. In <i>in vivo</i> testing, previous studies focused on the evaluation of toxicity of mesoporous silica particles in various organs. In contrast, we studied the change in the physical properties of SBA-15 microparticles depending on the duration after subcutaneous injection. The pristine SBA-15 microparticles injected into mice subcutaneously slowly degraded over time and lost ordered structure after 3 days. These findings represent the possible <i>in vivo</i> use of microsized mesoporous silica for drug delivery or vaccine platform after local injection

Aspartic Acid-Assisted Synthesis of Multifunctional Strontium-Substituted Hydroxyapatite Microspheres

Strontium-substituted hydroxyapatite (SrHAP) microspheres with three-dimensional (3D) structures were successfully prepared via hydrothermal method using self-assembled poly­(aspartic acid) (PASP) as a template. By controlling various parameters, including hydrothermal reaction time, amount of l-aspartic acid (l-Asp), and ratio of Sr ions, we were able to investigate the influences of the additive l-Asp on morphology and properties of final products as well as the role of self-assembled PASP template on the formation of HAP microspheres. The change in the amount of Sr substitution significantly affected the particle size, morphology, and concurrent surface area. This difference caused variation in the drug-release properties. In addition, substitution of Sr ions into Ca ion sites affected luminescence of HAP powders. Particularly, multifunctional SrHAP with molar ratios (Sr/[Ca+Sr]) of 0.25 possessed the strongest luminescence as well as superior drug-loading and sustained-releasing properties. These properties were associated with large surface area and large pore size of the SrHAP. This study suggests that the optical and structural properties of the HAP particles can be carefully tuned by controlling the amount of Sr ions doped into HAP particles during synthesis. This work provides new opportunities to synthesize HAP particles suitable for diverse applications including bone regeneration and drug delivery

Flexible and Transparent Metallic Grid Electrodes Prepared by Evaporative Assembly

We propose a novel approach to fabricating flexible transparent metallic grid electrodes via evaporative deposition involving flow-coating. A transparent flexible metal grid electrode was fabricated through four essential steps including: (i) polymer line pattern formation on the thermally evaporated metal layer onto a plastic substrate; (ii) rotation of the stage by 90° and the formation of the second polymer line pattern; (iii) etching of the unprotected metal region; and (iv) removal of the residual polymer from the metal grid pattern. Both the metal grid width and the spacing were systematically controlled by varying the concentration of the polymer solution and the moving distance between intermittent stop times of the polymer blade. The optimized Au grid electrodes exhibited an optical transmittance of 92% at 550 nm and a sheet resistance of 97 Ω/sq. The resulting metallic grid electrodes were successfully applied to various organic electronic devices, such as organic field-effect transistors (OFETs), organic light-emitting diodes (OLEDs), and organic solar cells (OSCs)

Direct Observation of Nanoparticle–Cancer Cell Nucleus Interactions

We report the direct visualization of interactions between drug-loaded nanoparticles and the cancer cell nucleus. Nanoconstructs composed of nucleolin-specific aptamers and gold nanostars were actively transported to the nucleus and induced major changes to the nuclear phenotype <i>via</i> nuclear envelope invaginations near the site of the construct. The number of local deformations could be increased by ultrafast, light-triggered release of the aptamers from the surface of the gold nanostars. Cancer cells with more nuclear envelope folding showed increased caspase 3 and 7 activity (apoptosis) as well as decreased cell viability. This newly revealed correlation between drug-induced changes in nuclear phenotype and increased therapeutic efficacy could provide new insight for nuclear-targeted cancer therapy

Ultrastable-Stealth Large Gold Nanoparticles with DNA Directed Biological Functionality

The stability of gold nanoparticles (AuNPs) in biological samples is very important for their biomedical applications. Although various molecules such as polystyrenesulfonate (PSS), phosphine, DNA, and polyethylene glycol (PEG) have been used to stabilize AuNPs, it is still very difficult to stabilize large AuNPs. As a result, biomedical applications of large (30–100 nm) AuNPs are limited, even though they possess more favorable optical properties and are easier to be taken up by cells than smaller AuNPs. To overcome this limitation, we herein report a novel method of preparing large (30–100 nm) AuNPs with a high colloidal stability and facile chemical or biological functionality, via surface passivation with an amphiphilic polymer polyvinylpyrrolidone (PVP). This PVP passivation results in an extraordinary colloidal stability for 13, 30, 50, 70, and 100 nm AuNPs to be stabilized in PBS for at least 3 months. More importantly, the PVP capped AuNPs (AuNP-PVP) were also resistant to protein adsorption in the presence of serum containing media and exhibit a negligible cytotoxicity. The AuNP-PVPs functionalized with a DNA aptamer AS1411 remain biologically active, resulting in significant increase in the uptake of the AuNPs (∼12 200 AuNPs per cell) in comparison with AuNPs capped by a control DNA of the same length. The novel method developed in this study to stabilize large AuNPs with high colloidal stability and biological activity will allow much wider applications of these large AuNPs for biomedical applications, such as cellular imaging, molecular diagnosis, and targeted therapy