Tunable Visible and Near‐IR Photoactivation of Light‐Responsive Compounds by Using Fluorophores as Light‐Capturing Antennas

Abstract

Although the corrin ring of vitamin B12 is unable to efficiently absorb light beyond 550 nm, it is shown that commercially available fluorophores can be used as antennas to capture long‐wavelength light to promote scission of the CoC bond at wavelengths up to 800 nm. The ability to control the molecular properties of bioactive species with long visible and near‐IR light has implications for drug delivery, nanotechnology, and the spatiotemporal control of cellular behavior.

Cell‐Mediated Assembly of Phototherapeutics

“…We recently described the long wavelength (>600 nm) photolysis of alkylcobalamins (alkyl-Cbl). [6] We now report the cell-mediated assembly of lipid-Cbl-drug and lipid-fluorophore conjugates in which the latter serve as long wavelength-capturing antennas that promote drug release.…”

“…[7] Our strategy to address this issue is depicted in Figure 1. Based on a previously demonstrated energy transfer between fluorophores and Cbls in covalently appended Cbl-fluorophore conjugates, [6] we decided to explore the premise that the cell-mediated assembly of C 18 -Cbldrug and C 18 -fluorophore conjugates could act in concert as a photo-responsive drug delivery system. Illumination of the fluorophore antenna at its λ max and subsequent energy transfer to the Cbl-drug moiety should result in cleavage of the weak Co-C bond, [6,8] thereby liberating the drug.…”

“…First, exposure of erythrocytes to C 18 -Cbl-TAM revealed even and extensive loading as assessed by widefield fluorescence microscopy. In addition, given the established photolytic sensitivity of the Co-C bond, [6,8,9] we were not surprised to find that imaging C 18 -Cbl-TAM on erythrocytes results in the rapid migration (<1 s) of TAM fluorescence from erythrocytes into solution (SI Figure S8). Tables S4 -S6).…”

“…We recently described the long wavelength (>600 nm) photolysis of alkylcobalamins (alkyl-Cbl). [6] We now report the cell-mediated assembly of lipid-Cbl-drug and lipid-fluorophore conjugates in which the latter serve as long wavelength-capturing antennas that promote drug release.Erythrocytes have been called the "champions of drug delivery" due to their biocompatibility, their long life span (120 days), and their size, which allows large quantities of drug to be conveyed relative to other carriers. [7] However, "practically useful controlled release from carrier RBC (red blood cells) remains an elusive goal".…”

“…Based on a previously demonstrated energy transfer between fluorophores and Cbls in covalently appended Cbl-fluorophore conjugates, [6] we decided to explore the premise that the cell-mediated assembly of C 18 -Cbldrug and C 18 -fluorophore conjugates could act in concert as a photo-responsive drug delivery system. Illumination of the fluorophore antenna at its λ max and subsequent energy transfer to the Cbl-drug moiety should result in cleavage of the weak Co-C bond, [6,8] thereby liberating the drug.A series of lipidated-Cbl (C 18 -Cbl) and C 18 -fluorophore derivatives were prepared ( Figure 2, SI Figures S1-S4 , Tables S3-S6 and Scheme S1). In the case of the Cbl derivatives, the C 18 moiety was appended to the 5 ribose -OH of Cbl using octadecylamine and carbonyl-ditriazole.…”