Eradication of HT-29 colorectal adenocarcinoma cells by controlled photorelease of CO from a CO-releasing polymer (photoCORP- 1) triggered by visible light through an optical fiber-based device

摘要

AbstractThe gaseous signaling molecule carbon monoxide (CO) has recently been recognized for its wide range of physiological activity as well as its antineoplastic properties. However, site-specific delivery of this noxious gas presents a major challenge in hospital settings. In this work, a visible light-sensitive CO-releasing molecule (photoCORM) derived from manganese(I) and 2-(quinolyl)benzothiazole (qbt) namely, [Mn(CO)3(qbt)(4-vpy)](CF3SO3) (1), has beenco-polymerized within a gas-permeable HEMA/EGDMA hydrogel. The resulting photoactive CO-releasing polymer (photoCORP-1) incorporates1such that neither the carbonyl complex nor its photoproduct(s) exits the polymer at any time. The material can be triggered to photorelease CO remotely by low-power broadband visible light (<1mWcm?2) with the aid of fiber optics technology. The CO photorelease rates of photoCORP-1(determined by spectrophotometry) can be modulated by both the concentration of1in the hydrogel and the intensity of the light. A CO-delivery device has been assembled to deliver CO to a suspension of human colorectal adenocarcinoma cells (HT-29) under the control of visible light and the extent of CO-induced apoptotic death of the cancer cells has been determined via Annexin V/Propidium iodide stain and flow cytometry. This photoactive CO-releasing polymer could find use in delivering controlled doses of CO to cellular targets such as malignant tissues in remote parts of the body.