Visible Light Controlled
Release of Anticancer Drug
through Double Activation of Prodrug
- Publication date
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Abstract
We designed and synthesized a novel double activatable
prodrug
system (drug–linker–deactivated photosensitizer), containing
a photocleavable aminoacrylate-linker and a deactivated photosensitizer,
to achieve the spatiotemporally controlled release of parent drugs
using visible light. Three prodrugs of CA-4, SN-38, and coumarin were
prepared to demonstrate the activation of deactivated photosensitizer
by cellular esterase and the release of parent drugs by visible light
(540 nm) via photounclick chemistry. Among these prodrugs, nontoxic
coumarin prodrug was used to quantify the release of parent drug in
live cells. About 99% coumarin was released from the coumarin prodrug
after 24 h of incubation with MCF-7 cells followed by irradiation
with low intensity visible light (8 mW/cm<sup>2</sup>) for 30 min.
Less toxic prodrugs of CA-4 and SN-38 killed cancer cells as effectively
as free drugs after the double activation