Visible Light Controlled Release of Anticancer Drug through Double Activation of Prodrug

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 2 ) for 30 min. Less toxic prodrugs of CA-4 and SN-38 killed cancer cells as effectively as free drugs after the double activation.

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

“…Strong fluorescence signals were observed at the tumor site at 3 h post-injection and could be maintained for up to 24 h. You et al synthesized three double activatable prodrugs of the CA-4, SN-38, and coumarin system (86a-c) that were first activated by intracellular esterase and then drug release was induced by light irradiation. 232 A photo-cleavable aminoacrylatelinker and a deactivated photosensitizer allowed the spatiotemporally controlled release of drugs by visible light irradiation. When the prodrug 86a was irradiated with very low intensity light (540 nm, 8 mW cm…”

Far-Red Light-Activatable Prodrug of Paclitaxel for the Combined Effects of Photodynamic Therapy and Site-Specific Paclitaxel Chemotherapy

“…40–43 The two functional moieties are connected with a singlet oxygen cleavable linker. Upon activation of the photosensitizer with deep tissue-penetrable visible and far-red light, the conjugate generates singlet oxygen that triggers immediate PDT damage and then cleaves the linker, releasing the chemotherapeutic drugs only at the site of illumination.…”

Emerging Strategies for Controlling Drug Release by Using Visible/Near IR Light

“…Recently, Bio et al demonstrated the ability of this method to cleave the aminoacrylate linker and release of the drug in cancer cells [50]. The pharmacological effects of the released drugs (e.g., combretastatin A-4, CA4) were also demonstrated both in vitro and in vivo (Figure 7) [51].…”