4.8 Article

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

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 264, Issue -, Pages 192-202

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.08.039

Keywords

Photoactive CO donor; HEMA hydrogel; Light triggering; Optical fiber; CO delivery; Colon cancer

Funding

  1. National Science Foundation [DMR-1409335]
  2. Direct For Mathematical & Physical Scien
  3. Division Of Materials Research [1409335] Funding Source: National Science Foundation

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The 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 been co-polymerized within a gas-permeable HEMA/EGDMA hydrogel. The resulting photoactive CO-releasing polymer (photoCORP-1) incorporates 1 such 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 (< 1 mW cm(-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 of 1 in 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.

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