Ultrasound responsive carbon monoxide releasing micelle

Osamah Alghazwat,Somayeh Talebzadeh,Jeremiah Oyer,Alicja Copik,Yi Liao

doi:10.1016/j.ultsonch.2020.105427

Osamah Alghazwat, Somayeh Talebzadeh + Show 3 more

Open Access

https://doi.org/10.1016/j.ultsonch.2020.105427

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Abstract

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.

Highlights

Carbon monoxide (CO) is produced naturally during heme catabo lism
[1] Studies have shown that CO has beneficial effects including anti-inflammatory, anti-apoptotic, anti-coagulative, anti-hypertensive, cell protective effects etc. [2,3,4,5,6,7,8,9,10] In the preclinical and animal studies, CO was delivered by inhalation or using CO releasing molecules (CO-RMs)
[11] CO-RMs are a group of compounds capable of releasing controlled quantities of CO in cellular systems. [12,13,14,15] The majority of CO-RMs studied are carbonyls of transition metals including both essential trace elements and non-physiological metals. [1,4,5,6,7,8,9,10] Some nonmetallic CO-RMs have been developed in recent years. [14,15,16,17,18,19,20,21,22] CO-RMs allows convenient administration of a certain dose of CO

Summary

Introduction

Carbon monoxide (CO) is produced naturally during heme catabo lism. As a gasotransmitter, CO plays important roles in many physio logical functions in the mammalian body. [1] Studies have shown that CO has beneficial effects including anti-inflammatory, anti-apoptotic, anti-coagulative, anti-hypertensive, cell protective effects etc. [2,3,4,5,6,7,8,9,10] In the preclinical and animal studies, CO was delivered by inhalation or using CO releasing molecules (CO-RMs). Previous studies have shown that pluronic micelles responded to US and released drugs encapsulated. A concentrated solution of cysteine was added to a CORM-2/pluronic micelle suspension.

Results

Conclusion