Intracellular protein delivery by hollow mesoporous silica capsules with a large surface hole.

We prepared cell membrane-permeable hollow mesoporous silica capsules (HMSCs) by a simple new method. CTAB micellar assembly in cholesterol emulsion gave rise to a novel capsular morphology of the HMSC particles. The HMSCs consisted of mesostructured silica walls with a large surface hole (25-50 nm) and the average particle dimension was 100-300 nm. They exhibited high surface areas of up to 719.3 m(2) g(-1) and a mesoporous range of pores of 2.4-2.7 nm. The surface-functionalized HMSCs could also be prepared by a similar co-condensation method using tetraethoxysilane with various organoalkoxysilane precursors in the presence of cholesterol. These organically modified HMSCs could be further modified on demand. For example, a carboxy-functionalized HMSC could be surface-functionalized by a green fluorescent 5-aminofluorescein (AFL) through an amidation reaction to afford a fluorescent AFL-HMSC. The hollow capsular morphology of the HMSCs with a large surface hole enabled us to develop very efficient intracellular delivery systems for membrane-impermeable ions, molecules, and various functional proteins. Non-covalent sequestration and delivery of proteins as well as covalent linkage of fluorescent molecules on the silica surface are effective for this system. The highly negatively charged green fluorescent probe mag-fluo-4 could be intracellularly delivered into HeLa cells by HMSC without any difficulty. The HMSCs could also effectively transport large functional proteins such as antibodies into HeLa cells. The efficiency of protein delivery by HMSC seems to be 3-22-fold higher than that of mesoporous silica nanospheres (MSNs) based on confocal laser scanning microscopy (CLSM) analysis.

[The impact of high apparent temperature on the increase of Summertime Disease-related mortality in Seoul: 1991-2000].

OBJECTIVES: The aim of this paper was to examine the relationship between the summertime (June to August) heat index, which quantifies the bioclimatic apparent temperature in sultry weather, and the daily disease-related mortality in Seoul for the period from 1991 to 2000. METHODS: The daily maximum (or minimum) summertime heat indices, which show synergetic apparent temperatures, were calculated from the six hourly temperatures and real time humidity data for Seoul from 1991 to 2000. The disease-related daily mortality was extracted with respect to types of disease, age and sex, etc. and compared with the time series of the daily heat indices. RESULTS: The summertime mortality in 1994 exceeded the normal by 626 persons. Specifically, blood circulation-related and cancer-related mortalities increased in 1994 by 29.7% (224 persons) and 15.4% (107 persons), respectively, compared with those in 1993. Elderly persons, those above 65 years, were shown to be highly susceptible to strong heat waves, whereas the other age and sex-based groups showed no significant difference in mortality. In particular, a heat wave episode on the 22nd of July 2004 (> 45 degrees C daily heat index) resulted in double the normal number of mortalities after a lag time of 3 days. Specifically, blood circulation-related mortalities, such as cerebral infraction, were predominant causes. Overall, a critical mortality threshold was reached when the heat index exceeded approximately 37 degrees C, which corresponds to human body temperature. A linear regression model based on the heat indices above 37 degrees C, with a 3 day lag time, accounted for 63% of the abnormally increased mortality (> or =+2 standard deviations). CONCLUSIONS: This study revealed that elderly persons, those over 65 years old, are more vulnerable to mortality due to abnormal heat waves in Seoul, Korea. When the daily maximum heat index exceeds approximately 37 degrees C, blood circulation-related mortality significantly increases. A linear regression model, with respect to lag-time, showed that the heat index based on a human model is a more dependable indicator for the prediction of hot weather-related mortality than the ambient air temperature.