No abstract

In studying the feasibility of developing tissue-targeted contrast media that can be administered as liquids and vaporized by an external stimulus such as ultrasound, we have investigated the properties of emulsions of nanometer-size particles containing perfluoropentane and 2H,3H-perfluoropentane. We found that the ultrasound intensity required to induce echographically significant vaporization can be controlled by changing the ratio of 2H,3H-perfluoropentane to perfluoropentane and that the intensity threshold increases as this ratio increases. Significant azeotropic phenomena were not observed when the perfluorocarbon mixtures were heated, which indicates that mechanisms other than azotropy are involved in the threshold change. The vaporization of 2H,3H-perfluoropentane may have been due not only to ultrasound energy but also to the energy deposited by ultrasonically induced bubbles of perfluoropentane. Our results might lead to a phase-shift contrast agent with controllable ultrasound energy for phase shifting.

The blood–brain barrier (BBB) has hampered the efficiency of nanoparticle delivery into the brain via conventional strategies. The widening of BBB tight junctions via focused ultrasound (FUS) offers a promising approach for enhancing the delivery of nanoparticles into the brain. However, there is currently an insufficient understanding of how nanoparticles pass through the opened BBB gaps. Here we investigated the size-dependence of nanoparticle delivery into the brain assisted by FUS-induced BBB opening, using gold nanoparticles (AuNPs) of 3, 15, and 120 nm diameter. For 3- and 15-nm AuNPs, FUS exposure significantly increased permeation across an in vitro BBB model by up to 9.5 times, and the permeability was higher with smaller diameter. However, in vivo transcranial FUS exposure in mice demonstrated that smaller particles were not necessarily better for delivery into the brain. Medium-sized (15 nm) AuNPs showed the highest delivery efficiency (0.22% ID), compared with 3- and 120-nm particles. A computational model suggested that this optimum size was determined by the competition between their permeation through opened BBB gaps and their excretion from blood. Our results would greatly contribute to designing nanoparticles for their delivery into the brain for the treatment of central nervous system diseases.

Laparoscopic surgery may be an acceptable alternative treatment option to conventional open surgery for rectal cancer.

LADG is advantageous over ODG because it results in lesser blood loss, is less painful, and is associated with a low risk of complications. Additional RCTs that compare LADG and ODG and investigate the long-term oncological outcomes of LADG are required to determine the advantages of LADG over ODG.