Photo-controlled delivery of a potent analogue of doxorubicin

Abstract

Highly cytotoxic agents have found an important niche in targeted anticancer therapy. Here we develop a new light release strategy for the targeting of one of these agents, 2-pyrrolinodoxorubicin, showing dramatic enhancements in toxicity with light and single digit nM potency.

Green-Light Activatable, Water-Soluble Red-Shifted Coumarin Photocages

“…rendering them inactive. Upon removal of these photolabile moieties by irradiation with a suitable wavelength the activity of the function, substrate reinstates. − Examples of the use of photocaged compounds include nucleotides, neurotransmitters, proteins, pharmaceuticals, , ions, and many other small molecules . Most photocages are based on o -nitrobenzyl or coumarinylmethyl scaffolds .…”

Targeted Cancer Therapy Using Compounds Activated by Light

“…Hartman and coworkers studied the photocaging of 2-pyrrolino doxorubicin (2P-Dox) (10), a derivative of the standard doxorubicin, starting from its known diacetoxy prodrug [42]. Photorelease upon UV irradiation showed 88% release after 60 min irradiation, which corroborated by MS and HPLC results (20 mM in PBS, 380 nm, 9.0 mW/cm 2 ).…”

“…Under dark conditions, the free Ru II complexes showed no cytotoxicity (IC 50 > 100 µM); however, two of them showed modest cytotoxicity (IC 50 = 65-83 µM) upon light irradiation on HeLa and MRC-5. Two of the fully armed NLS constructs (42,43) showed an accumulation in the nucleus, two NLS constructs showing dark toxicity as well (not increased by UV irradiation), and overall hardly any selectivity was found for this design. The cellular localization of BBN-conjugates depended on the Ru II -ligands (nucleus/cytoplasm).…”

Caged Oxime Reactivators Designed for the Light Control of Acetylcholinesterase Reactivation†

“…et al (19) and Hess. et al (20) as described in their influential works and has greatly expanded to a broad range of biological targets and functions (18) from cellular signaling (21)(22)(23)(24), imaging (14), optogenetics (25)(26)(27), gene replication or regulation (16,25,28) to drug delivery systems (29)(30)(31).…”