» Articles » PMID: 32713525

A Near-infrared Light-mediated Cleavable Linker Strategy Using the Heptamethine Cyanine Chromophore

Overview
Journal Methods Enzymol
Specialty Biochemistry
Date 2020 Jul 28
PMID 32713525
Citations 7
Authors
Affiliations
Soon will be listed here.
Abstract

Optical methods offer the potential to manipulate living biological systems with exceptional spatial and temporal control. Caging bioactive molecules with photocleavable functional groups is an important strategy that could be applied to a range of problems, including the targeted delivery of otherwise toxic therapeutics. However existing approaches that require UV or blue light are difficult to apply in organismal settings due to issues of tissue penetration and light toxicity. Photocaging groups built on the heptamethine cyanine scaffold enable the targeted delivery of bioactive molecules using near-IR light (up to 780nm) in live animal settings. Here we provide a detailed procedure demonstrating the utility of the heptamethine cyanine caging group to create a light-cleavable linker between an antibody, panitumumab, and a therapeutic small molecule in the duocarmycin class of natural products. Descriptions of the design and synthesis of the small molecule component, assembly of the antibody conjugate, in vitro analysis of uncaging, in vivo imaging, and impact on tumor progression are provided.

Citing Articles

Taking phototherapeutics from concept to clinical launch.

Vickerman B, Zywot E, Tarrant T, Lawrence D Nat Rev Chem. 2023; 5(11):816-834.

PMID: 37117665 PMC: 8493544. DOI: 10.1038/s41570-021-00326-w.


Multimeric RGD-Based Strategies for Selective Drug Delivery to Tumor Tissues.

Cossu J, Thoreau F, Boturyn D Pharmaceutics. 2023; 15(2).

PMID: 36839846 PMC: 9961187. DOI: 10.3390/pharmaceutics15020525.


Development of Photoremovable Linkers as a Novel Strategy to Improve the Pharmacokinetics of Drug Conjugates and Their Potential Application in Antibody-Drug Conjugates for Cancer Therapy.

Johan A, Li Y Pharmaceuticals (Basel). 2022; 15(6).

PMID: 35745573 PMC: 9230074. DOI: 10.3390/ph15060655.


Electromagnetic Waves Can Help Improve the Rate of Increase of Milk Feeds Per Day in Premature Infants With Necrotizing Enterocolitis: A Pilot Trial.

Liu X, Zhang X, Li L, Wang J, Wu L Front Pediatr. 2022; 10:775428.

PMID: 35356438 PMC: 8960040. DOI: 10.3389/fped.2022.775428.


Site-Specific and Enzymatic Cross-Linking of sgRNA Enables Wavelength-Selectable Photoactivated Control of CRISPR Gene Editing.

Zhang D, Liu L, Jin S, Tota E, Li Z, Piao X J Am Chem Soc. 2022; 144(10):4487-4495.

PMID: 35257575 PMC: 9469474. DOI: 10.1021/jacs.1c12166.


References
1.
Li J, Pu K . Semiconducting Polymer Nanomaterials as Near-Infrared Photoactivatable Protherapeutics for Cancer. Acc Chem Res. 2020; 53(4):752-762. DOI: 10.1021/acs.accounts.9b00569. View

2.
Zhang R, Schroeder A, Grudzinski J, Rosenthal E, Warram J, Pinchuk A . Beyond the margins: real-time detection of cancer using targeted fluorophores. Nat Rev Clin Oncol. 2017; 14(6):347-364. PMC: 5683405. DOI: 10.1038/nrclinonc.2016.212. View

3.
Solomek T, Wirz J, Klan P . Searching for Improved Photoreleasing Abilities of Organic Molecules. Acc Chem Res. 2015; 48(12):3064-72. DOI: 10.1021/acs.accounts.5b00400. View

4.
Shell T, Shell J, Rodgers Z, Lawrence D . Tunable visible and near-IR photoactivation of light-responsive compounds by using fluorophores as light-capturing antennas. Angew Chem Int Ed Engl. 2013; 53(3):875-8. PMC: 4036634. DOI: 10.1002/anie.201308816. View

5.
Gorka A, Yamamoto T, Zhu J, Schnermann M . Cyanine Photocages Enable Spatial Control of Inducible Cre-Mediated Recombination. Chembiochem. 2018; 19(12):1239-1243. PMC: 6344125. DOI: 10.1002/cbic.201800061. View