Phototriggered Secretion of Membrane Compartmentalized Bioactive Agents.

A strategy for the light-activated release of bioactive compounds (BODIPY, colchicine, paclitaxel, and methotrexate) from membrane-enclosed depots is described. We have found that membrane-permeable bioagents can be rendered membrane impermeable by covalent attachment to cobalamin (Cbl) through a photocleavable linker. These Cbl-bioagent conjugates are imprisoned within lipid-enclosed compartments in the dark, as exemplified by their retention in the interior of erythrocytes.

Cell-mediated assembly of phototherapeutics.

Light-activatable drugs offer the promise of controlled release with exquisite temporal and spatial resolution. However, light-sensitive prodrugs are typically converted to their active forms using short-wavelength irradiation, which displays poor tissue penetrance. We report herein erythrocyte-mediated assembly of long-wavelength-sensitive phototherapeutics.

Long-wavelength fluorescent reporters for monitoring protein kinase activity.

In vivo optical imaging must contend with the limitations imposed by the optical window of tissue (600-1000 nm). Although a wide array of fluorophores are available that are visualized in the red and near-IR region of the spectrum, with the exception of proteases, there are few long wavelength probes for enzymes. This situation poses a particular challenge for studying the intracellular biochemistry of erythrocytes, the high hemoglobin content of which optically obscures subcellular monitoring at wavelengths less than 600 nm.

Lipid pools as photolabile "protecting groups": design of light-activatable bioagents.

Inactive in the membrane: Lipidated light-responsive constructs that sequester bioagents (R, see scheme) to the membranes of organelles and cells have been constructed. When membrane-bound, the bioagent is not susceptible to processing by its biological target. Photolysis releases the bioagent from its membrane anchor and thereby renders it biologically active.