Single-Chromophore-Based Therapeutic Agent Enables Green-Light-Triggered Chemotherapy and Simultaneous Photodynamic Therapy to Cancer Cells

Abstract

A new type of single-chromophore-based photoactivatable prodrug (B-Cbl-3) enabling green-light-triggered chemotherapy and simultaneous photodynamic therapy with superb therapeutic efficacy was developed by conjugating a photoactive BODIPY derivative with an antitumor chlorambucil moiety. The optimized BODIPY moiety markedly enabled high efficient photogeneration of 1 O 2 and fluorescence emission with distinct colors before and after photorelease of chlorambucil. The preliminary biological experiment results have verified the efficient photorelease of chlorambucil from B-Cbl-3 and the huge contrast in cytotoxicity between them, superior combined therapeutic performance based on extraordinary low doses of drug and light irradiation, and ratiometric fluorescence imaging for in situ monitoring drug release. The salient superiority of B-Cbl-3 regarding alleviating the attenuation of triggering light caused by optically turbid tissue that short-wavelength lights typically encounters has also been verified.

Visible-to-NIR-Light Activated Release: From Small Molecules to Nanomaterials

“…The photorelease of diverse functional groups, including primary and secondary amines 794 , 805 , 809 , 810 , 812 (as carbamates), carboxylic acids, 295 , 794 , 795 , 798 , 802 , 804 , 806 − 808 alcohols 794 , 798 , 805 (as carbonic acid esters 794 or ethers 798 , 801 , 805 ), halogens, 798 hydroxylamines, 803 thiocarbamic acid, 799 thioacetic acid, 798 and thiols 800 ( Figure 15 ) from BODIPY-based PPGs, has been reported. The liberation efficiency of LGs correlated well with the p K a of their conjugate acids, 794 , 798 , 809 and the photoreaction quantum efficiency of unsubstituted BODIPYs (other than 1,3,5,7-tetramethyl derivatives) was moderate to low.…”

Photoremovable Protecting Groups: Across the Light Spectrum to Near-Infrared Absorbing Photocages

“…[89] Other noteworthy examples include targeted release of the protonophore 2,4-dinitrophenol in mitochondria, protein synthesis inhibitor puromycin in the endoplasmic reticulum [90] and photocontrolled delivery of cytotoxic chlorambucil and cathepsin B inhibitor to cells. [91,92] Further efforts have also been devoted to the improvement of cellular uptake of BODIPY PPGs, enabling specific subcellular targeting, and to improve their solubility in water. [87,90] What lies ahead?…”

Photocleavage‐based Photoresponsive Drug Delivery†

“…Though the potential cytotoxicity caused by some of byproducts might restrict the clinical translation of PPGs, efforts have been made to solve this problem, such as the development of novel 2-nitrobenzyl derivatives whose byproducts are less toxic (39). In several studies, the toxicity of BOD-IPY and Ru complexes after light irradiation has been utilized to exert synergistic effect with chemotherapy drugs (37,40). Moreover, with precise control of light irradiation, the photocleavage process will be restricted at the disease sites, minimizing adverse effects caused by byproducts in normal tissues.…”