Carbon monoxide release from ultrasound-sensitive microbubbles improves endothelial cell growth.

Carbon monoxide is a gasotransmitter that may be beneficial for vascular tissue engineering and regenerative medicine strategies because it can promote endothelial cell (EC) proliferation and migration by binding to heme-containing compounds within cells. For example, CO may be beneficial for vascular cognitive impairment and dementia because many patients' disrupted blood-brain barriers do not heal naturally. However, control of the CO dose is critical, and new controlled delivery methods need to be developed. This study developed ultrasound-sensitive microbubbles with a carefully controlled precipitation technique, loaded them with CO, and assessed their ability to promote EC proliferation and function. Microbubbles fabricated with perfluoropentane exhibited good stability at room temperature, but they could still be ruptured and release CO in culture with application of ultrasound. Microbubbles synthesized from the higher boiling point compound, perfluorohexane, were too stable at physiological temperature. The lower-boiling point perfluoropentane microbubbles had good biocompatibility and appeared to improve VE-cadherin expression when CO was loaded in the bubbles. Finally, tissue phantoms were used to show that an imaging ultrasound probe can efficiently rupture the microbubbles and that the CO-loaded microbubbles can improve EC spreading and proliferation compared to control conditions without microbubbles as well as microbubbles without application of ultrasound. Overall, this study demonstrated the potential for use of these ultrasound-sensitive microbubbles for improving blood vessel endothelialization.

Photoacid for releasing carbon dioxide from sorbent.

Carbon dioxide (CO2) is the most important greenhouse gas that causes global warming. Different sorbents, e.g. amines have been applied to capture CO2. Sorbent regeneration, which is currently conducted by thermal processes, is the most energy consuming step. In this work, we studied a photoacid, which can reversibly increase the acidity of a solution under light, and consequently lead to CO2 release. The photoactivity, acidity and solubility of the photoacid was tuned for CO2 release by structural design. The photoacid was mixed with morpholine, which is a well-studied amine for CO2 capture. Results showed that an aqueous solution containing the mixture can repeatedly capture and release CO2 under moderate irradiation of visible light. The CO2 released was nearly the same to that was captured, which indicates the high efficiency of this method.

Ultrasound responsive carbon monoxide releasing micelle.

Carbon monoxide (CO), an endogenously produced gasotransmitter, has shown various therapeutic effects in previous studies. In this work, we developed an ultrasound responsive micelle for localized CO delivery. The micelle is composed of a pluronic shell and a core of a CO releasing molecule, CORM-2. The mechanism is based on the ultrasound response of pluronics, and the reaction between CORM-2 and certain biomolecules, e.g. cysteine. The latter allows CO release without significantly breaking the micelles. In a 3.5 mM cysteine solution, the micelles released low level of CO, indicating effective encapsulation of CORM-2. Treatment with a low intensity, non-focused ultrasound led to four times as much CO as the sample without ultrasonication, which is close to that of unencapsulated CORM-2. Significantly reduced proliferation of prostate cancer cells (PC-3) was observed 24 h after the PC-3 cells were treated with the CORM-2 micelles followed by ultrasound activation.

Poly(butyl cyanoacrylate) nanoparticle containing an organic photoCORM.

Carbon monoxide (CO) is a gasotransmitter, which has shown therapeutic effects in recent studies. Photo carbon monoxide releasing molecules (PhotoCORMs) allow the delivery of CO to be controlled by light. In this work, a new organic photoCORM DK4 is studied. DK4 is a diketone type photoCORM, which releases two CO molecules under visible light and simultaneously generates a fluorescent anthracene derivative. However, this type of CORM suffers from a deactivating hydration reaction and often needs to be incorporated in polymers or micelles. The two highly hydrophobic tert-butyl groups of DK4 protect it from the hydration reaction. DK4 functions in 1% DMSO aqueous solution, in which other DKs are deactivated. DK4 was incorporated in a poly(butyl cyanoacrylate) (PBCA) nanoparticle. PBCA has been used as a tissue adhesive and has been extensively studied for delivery of drugs to the brain. The PBCA/DK4 nanoparticle showed good photoactivity and low cytotoxicity, and thus is a promising material for studying the biomedical effects of CO.