The degradation of colloidal mesoporous silica nanoparticles (CMPS) is quite important for the design of stable catalyst supports and biodegradable drug delivery systems carriers. The degradation of various silica nanoparticles in static aqueous systems was investigated. The condition was achieved through the use of a dialysis tube. Four types of CMPS with different particle diameters (ca. 20−80 nm) were newly prepared from tetraalkoxysilanes (Si(OR) 4 , R = Me, Et, Pr, and Bu) at different hydrolysis rates by a one-pot synthesis. Larger particles were formed by using tetraalkoxysilanes at slower hydrolysis rates because particle growth dominates nucleation. The degradation of CMPS is independent of diameter differences. The degradation rate of CMPS is higher than that of colloidal nonporous silica nanoparticles with smaller diameters because of the presence of mesopores. CMPS are also more degradable than aggregated CMPS because of colloidal dispersity. Moreover, it was confirmed for the first time that the degradation simultaneously proceeds from the outer as well as the inner surfaces of CMPS and that the mesostructure and morphology are partly retained even after more than half of the CMPS are degraded. The information on the degradation reported here is quite useful for the design of silica-based nanomaterials with tunable degradability/stability.

Aqueous colloidal mesoporous nanoparticles with ethenylene-bridged silsesquioxane frameworks with a uniform diameter of ∼20 nm were prepared from bis(triethoxysilyl)ethenylene in a basic aqueous solution containing cationic surfactants. The nanoparticles, which had higher hydrolysis resistance under aqueous conditions, showed lower hemolytic activity toward bovine red blood cells than colloidal mesoporous silica nanoparticles.

A synthetic polymer gel–based insulin delivery device provides an artificial pancreas–like function in healthy and diabetic mice.

Particle size control of colloidal mesoporous silica nanoparticles (CMPS) in a very wide range is quite significant for the design of CMPS toward various applications, such as catalysis and drug delivery. Various types of CMPS and their precursors (colloidal mesostructured silica nanoparticles (CMSS)) with different particle sizes (ca. 20-700 nm) were newly prepared from tetraalkoxysilanes with different alkoxy groups (Si(OR)4, R = Me, Et, Pr, and Bu) in the presence of alcohols (R'OH, R' = Me, Et, Pr, and Bu) as additives. CMSS with larger particle size were obtained by using tetrabutoxysilane (TBOS) and by increasing the amount of BuOH, which is explained by both the difference in the hydrolysis rates of tetraalkoxysilanes themselves and the effect of added alcohols on the hydrolysis rates of tetraalkoxysilanes. Larger amounts of alcohols with longer alkyl chains decrease the hydrolysis rates of tetraalkoxysilanes and the subsequent formation rates of silica species. Thus, the preferential particle growth of CMSS to nucleation occurs, and larger CMSS are formed. Highly dispersed CMPS were prepared by the removal of surfactants of CMSS by dialysis which can lead to the preparation of CMPS without aggregation. Therefore, the particle size control through the tuning of the hydrolysis rate of tetraalkoxysilanes can be conducted by a one-pot and easy approach. Even larger CMPS (ca. 700 nm in size) show relatively high dispersibility. This dispersibility will surely contribute to the design of materials both retaining nanoscale characteristics and avoiding various nanorisks.

Mesoporous silica nanoparticles are promising materials for various applications, such as drug delivery and catalysis, but the functional roles of surfactants in the formation and preparation of mesostructured silica nanoparticles (MSN-as) remain to be seen. It was confirmed that the molar ratio of cationic surfactants to Si of alkoxysilanes (Surf/Si) can affect the degree of mesostructure formation (i.e., whether the mesochannels formed inside the nanoparticles actually pass through the outer surface of the particles), the particle diameter, and the dispersibility of MSN-as. Wormhole-like mesostructures formed with low Surf/Si ratios; however, the mesopores did not pass through the outer surface of the particles completely. At high Surf/Si ratios, the mesostructures extended. The particle diameter was 100 nm or larger at low Surf/Si ratios, and the primary particle diameter decreased as the Surf/Si ratio increased. This was because the surfactants enhanced the dispersity of the alkoxysilanes in water and the hydrolysis rate of the alkoxysilanes became faster, leading to an increased nucleation as compared to the particle growth. Moreover, primary particles aggregated at low Surf/Si ratios because of the hydrophobic interactions among the surfactants that were not involved in the mesostructure formation but were adsorbed onto the nanoparticles. At high Surf/Si ratios, the surfactant micelles were adsorbed on the surface of primary particles (admicelles), resulting in the dispersion of the particles due to electrostatic repulsion. In particular, molar ratios of 0.13 or higher were quite effective for the preparation of highly dispersed MSN-as. Surfactants played important roles in the mesostructure formation, decreasing the particle diameters, and the dispersibility of the particles. All of these factors were considerably affected by the Surf/Si ratio. The results suggested novel opportunities to control various colloidal mesostructured nanoparticles from the aspects of composition, structure, and morphology and will also be useful in the development of novel methods to prepare nanomaterials in various fields.

We have previously described antibody 9.3 which recognizes a 44-kDa polypeptide designated Tp44 expressed on 70-80% of peripheral blood T cells, including nearly all CD4+ cells and some CD8+ cells. Whereas the 9.3+ population contains helper cells, cytotoxic T cell precursors and cytotoxic T cell effectors, the 9.3- population has been reported in several models to contain precursors for suppressor cells. In this report, we demonstrate that 9.3- lymphocytes express CD11, an antigen which is also present on monocytes and granulocytes. Among lymphoid cells, Tp44 and CD11 represent markers that identify reciprocal, nonoverlapping subsets, each of which contains both CD8+ cells and CD4+ cells. With Tp44 and CD11, and CD4 and CD8, the development and function of T cells can thus be examined within the framework of two distinct systems of reciprocally expressed antigens.

No abstract

Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. This multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with R/R aggressive ATL (acute, lymphoma, unfavorable chronic type). Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. The primary endpoint was met with a centrally reviewed ORR of 48.0% (90% CI, 30.5% to 65.9%), including 5 complete and 7 partial remissions. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Treatment-emergent adverse events (TEAEs) were manageable. TEAEs that occurred in ≥20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Grade ≥3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL.