Nitric oxide (NO) is a ubiquitous molecule in the body. Because of its multiple pathophysiologic roles, the potential for treating various diseases by the exogenous administration of NO has been under intensive investigation. However, the unstable, radical nature of NO poses a major challenge to the effective delivery of NO. Previously, silica nanoparticles synthesized by the traditional method have been developed into NO-carrying systems. In the present study, for the first time NO-carrying silica nanoparticles were prepared from a single silica precursor using a simple nanoprecipitation method. (3-Mercaptopropyl)-trimethoxysilane (MPTMS) was used as the sole silane source, which was subjected to acid-catalyzed S-nitrosation and condensation reactions in a one-pot organic phase. S-Nitroso silica nanoparticles (SNO-SiNPs) were then produced by injecting a smaller quantity of the organic phase into a larger amount of water without surfactants. Various preparation parameters were tested to obtain optimized conditions. Moreover, a phase diagram demonstrating the ouzo effect was constructed. The prepared SNO-SiNPs were spherical particles with a tunable size in the range of 100-400 nm. The nanoparticles in aqueous dispersions exhibited high colloid stability, possibly resulting from highly negatively charged surfaces. The result of solid-state (29)Si NMR shows the predominance of T(2) and T(3) silicon structures, suggesting that nanoparticles were formed from polycondensed silica species. In conclusion, NO-loaded silica nanoparticles have been directly prepared from a single silane precursor using a surfactant-free, low-energy, one-step nanoprecipitation approach. The method precludes the need for the initial formation of bare particles and subsequent functionalization steps.

In this article, we report a novel, nanoprecipitation-based method for preparing silica nanoparticles with thiol and amine cofunctionalization. (3-Mercaptopropyl)trimethoxysilane (MPTMS) and 3-aminopropyltrimethoxysilane (APTMS) were used as the organosilane precursors, which were subjected to acid-catalyzed polycondensation in an organic phase containing a water-miscible solvent (e.g., dimethyl sulfoxide). A pale colloidal solution could be immediately formed when the preincubated organic phase was directly injected into water. The initial composition ratio between MPTMS and APTMS is an important factor governing the formation of nanoparticles. Specifically, large, unstable micrometer-sized particles were formed for preparation using MPTMS as the sole silane source. In contrast, when APTMS was used alone, no particles could be formed. By reducing the fraction of APTMS (or increasing that of MPTMS) in the initial mixture of organosilanes, the formation of nanometer-sized particles occurred at a critical fraction of APTMS (i.e., 25%). Remarkably, a tiny fraction (e.g., 1%) of APTMS was sufficient to produce stable nanoparticles with a hydrodynamic diameter of about 200 nm. Other factors that would also affect particle formation were determined. Moreover, an interesting temperature effect on particle formation was observed. The TEM micrographs show spherical nanospheres with mean sizes of 130-150 nm in diameter. The solid-state (29)Si NMR spectra demonstrate that the hybrid silica materials contain fully and partially condensed silicon structures. The bifunctionalized silica nanoparticles have positive zeta potentials whose magnitudes are positively correlated with the amount of APTMS. The total thiol content, however, is negatively correlated with the amount of APTMS. The cationic nanoparticles can bind an antisense oligonucleotide in a composition-dependent manner.

Codelivery of nitric oxide (NO) and drugs based on a single nanocarrier is a promising therapeutic strategy. Here, we report a one-step nanoprecipitation method to generate nanoparticles that possess simultaneous NO-donating and doxorubicin releasing properties. S-Nitroso polysilsesquioxane acts like an avid "drug sponge" that attracts drug molecules into nanospheres.

Amphiphilic drugs are therapeutic agents whose molecular structures contain both hydrophobic and hydrophilic portions. Here we report a systematic study on how amphiphilic drugs can assist in silica nanoprecipitation. 3-Mercaptopropyltrimethoxysilane (MPTMS) was used as the sole silica material and 12 amphiphilic drugs spanning a wide spectrum of therapeutic categories were included. MPTMS polycondensation was conducted in a DMSO-based organic phase. After a sufficient time, particle formation was induced by injecting a small amount of the organic phase into a water solution containing various amphiphiles. The results show that all amphiphilic drugs studied exerted concentration-dependent facilitating effect on nanoparticle formation. Under certain preparation conditions, the particle solution showed physical stability over a long period and the formed particles could be as small as 100 nm. By systematically varying drug concentrations and injection volumes, the ability of each amphiphile to promote nanoprecipitation can be quantified and compared, based on two novel indices: the area under the critical volume-concentration curve (AUC) and the critical stabilization concentration (CSC). We demonstrate that both ability indices significantly correlated with the drug's log P and critical micelle concentrations (CMC). Furthermore, we have optimized the aging and particle purification condition and extensively characterized our system through comprehensive TEM and zeta-potential measurements, as well as determinations for drug entrapment and release. In conclusion, we have established a quantitative structure-activity relationship for amphiphilic small-molecular drugs in their ability to interact with poly(mercaptopropyl)silsesquioxane species and form nanoparticles via solvent shifting. We speculate that both hydrophobic and electrostatic interactions play important roles in the formation and stabilization of nanoparticles.

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