Enhanced Cell Death Imaging Using Multivalent Zinc(II)-bis(dipicolylamine) Fluorescent Probes

Overview

Journal Mol Pharm

Publisher American Chemical Society

Specialty Pharmacology

Date 2013 Aug 7

PMID 23915311

Citations 11

Authors

Bryan A Smith

Kara M Harmatys

Shuzhang Xiao

Erin L Cole

Adam J Plaunt

William Wolter

Mark A Suckow

Bradley D Smith

Affiliations

Soon will be listed here.

Abstract

There is a clinical need for imaging technologies that can accurately detect cell death in a multitude of pathological conditions. Zinc(II)-bis(dipicolylamine) (Zn2BDPA) coordination complexes are known to associate with the anionic phosphatidylserine that is exposed on the surface of dead and dying cells, and fluorescent monovalent Zn2BDPA probes are successful cell death imaging agents. This present study compared the membrane targeting ability of two structurally related deep-red fluorescent probes, bis-Zn2BDPA-SR and tetra-Zn2BDPA-SR, with two and four appended Zn2BDPA units, respectively. Vesicle and cell microscopy studies indicated that a higher number of Zn2BDPA targeting units improved probe selectivity for phosphatidylserine-rich vesicles, and increased probe localization at the plasma membrane of dead and dying cells. The fluorescent probes were also tested in three separate animal models, (1) necrotic prostate tumor rat model, (2) thymus atrophy mouse model, and (3) traumatic brain injury mouse model. In each case, there was more tetra-Zn2BDPA-SR accumulation at the site of cell death than bis-Zn2BDPA-SR. The results indicate that multivalent Zn2BDPA probes are promising molecules for effective imaging of cell death processes in cell culture and in living subjects.

Citing Articles

Click Chemistry and Multicomponent Reaction for Linker Diversification of Zinc Dipicolylamine-Based Drug Conjugates.

Tsai C, Chiu T, Chen C, Hsu C, Tsai Y, Yeh T Front Chem. 2022; 9:822587.

PMID: 35242746 PMC: 8886374. DOI: 10.3389/fchem.2021.822587.

Time-lapse imaging of cell death in cell culture and whole living organisms using turn-on deep-red fluorescent probes.

Jarvis T, Roland F, Dubiak K, Huber P, Smith B J Mater Chem B. 2019; 6(30):4963-4971.

PMID: 30858977 PMC: 6407891. DOI: 10.1039/C8TB01495G.

Antiplasmodial activity of targeted zinc(II)-dipicolylamine complexes.

Rice D, Betancourt Mendiola M, Murillo-Solano C, Checkley L, Ferdig M, Pizarro J Bioorg Med Chem. 2017; 25(10):2754-2760.

PMID: 28377170 PMC: 5443346. DOI: 10.1016/j.bmc.2017.03.050.

Preassembled Fluorescent Multivalent Probes for the Imaging of Anionic Membranes.

Roland F, Peck E, Rice D, Smith B Bioconjug Chem. 2017; 28(4):1093-1101.

PMID: 28125214 PMC: 5476362. DOI: 10.1021/acs.bioconjchem.7b00012.

Imaging and therapeutic applications of zinc(ii)-dipicolylamine molecular probes for anionic biomembranes.

Rice D, Clear K, Smith B Chem Commun (Camb). 2016; 52(57):8787-801.

PMID: 27302091 PMC: 4949593. DOI: 10.1039/c6cc03669d.

References

Konstantinidis K, Whelan R, Kitsis R . Mechanisms of cell death in heart disease. Arterioscler Thromb Vasc Biol. 2012; 32(7):1552-62. PMC: 3835661. DOI: 10.1161/ATVBAHA.111.224915. View

Krachler A, Ham H, Orth K . Outer membrane adhesion factor multivalent adhesion molecule 7 initiates host cell binding during infection by gram-negative pathogens. Proc Natl Acad Sci U S A. 2011; 108(28):11614-9. PMC: 3136308. DOI: 10.1073/pnas.1102360108. View

Frey B, Schildkopf P, Rodel F, Weiss E, Munoz L, Herrmann M . AnnexinA5 renders dead tumor cells immunogenic--implications for multimodal cancer therapies. J Immunotoxicol. 2009; 6(4):209-16. DOI: 10.3109/15476910903204058. View

Gassensmith J, Baumes J, Smith B . Discovery and early development of squaraine rotaxanes. Chem Commun (Camb). 2009; (42):6329-38. PMC: 2854661. DOI: 10.1039/b911064j. View

Hanshaw R, Lakshmi C, Lambert T, Johnson J, Smith B . Fluorescent detection of apoptotic cells by using zinc coordination complexes with a selective affinity for membrane surfaces enriched with phosphatidylserine. Chembiochem. 2005; 6(12):2214-20. DOI: 10.1002/cbic.200500149. View

Thompson C . Apoptosis in the pathogenesis and treatment of disease. Science. 1995; 267(5203):1456-62. DOI: 10.1126/science.7878464. View

Sun X, Dinsdale D, Snowden R, Cohen G, Skilleter D . Characterization of apoptosis in thymocytes isolated from dexamethasone-treated rats. Biochem Pharmacol. 1992; 44(11):2131-7. DOI: 10.1016/0006-2952(92)90339-k. View

Stoffel M, Blau C, Reinl H, Breidt J, Gersonde K, Baethmann A . Identification of brain tissue necrosis by MRI: validation by histomorphometry. J Neurotrauma. 2004; 21(6):733-40. DOI: 10.1089/0897715041269678. View

Vaux D, Korsmeyer S . Cell death in development. Cell. 1999; 96(2):245-54. DOI: 10.1016/s0092-8674(00)80564-4. View

10.

Chekeni F, Elliott M, Sandilos J, Walk S, Kinchen J, Lazarowski E . Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature. 2010; 467(7317):863-7. PMC: 3006164. DOI: 10.1038/nature09413. View

11.

Bockbrader K, Tan M, Sun Y . A small molecule Smac-mimic compound induces apoptosis and sensitizes TRAIL- and etoposide-induced apoptosis in breast cancer cells. Oncogene. 2005; 24(49):7381-8. DOI: 10.1038/sj.onc.1208888. View

12.

Reed J . Dysregulation of apoptosis in cancer. J Clin Oncol. 1999; 17(9):2941-53. DOI: 10.1200/JCO.1999.17.9.2941. View

13.

Raslan F, Schwarz T, Meuth S, Austinat M, Bader M, Renne T . Inhibition of bradykinin receptor B1 protects mice from focal brain injury by reducing blood-brain barrier leakage and inflammation. J Cereb Blood Flow Metab. 2010; 30(8):1477-86. PMC: 2949241. DOI: 10.1038/jcbfm.2010.28. View

14.

Smith B, Xiao S, Wolter W, Wheeler J, Suckow M, Smith B . In vivo targeting of cell death using a synthetic fluorescent molecular probe. Apoptosis. 2011; 16(7):722-31. PMC: 3144473. DOI: 10.1007/s10495-011-0601-5. View

15.

Cole E, Arunkumar E, Xiao S, Smith B, Smith B . Water-soluble, deep-red fluorescent squaraine rotaxanes. Org Biomol Chem. 2011; 10(30):5769-73. PMC: 4015105. DOI: 10.1039/c2ob06783h. View

16.

White A, Gray B, Pak K, Smith B . Deep-red fluorescent imaging probe for bacteria. Bioorg Med Chem Lett. 2012; 22(8):2833-6. PMC: 3321076. DOI: 10.1016/j.bmcl.2012.02.078. View

17.

Smith B, Smith B . Biomarkers and molecular probes for cell death imaging and targeted therapeutics. Bioconjug Chem. 2012; 23(10):1989-2006. PMC: 3477794. DOI: 10.1021/bc3003309. View

18.

Collins B, Paulson J . Cell surface biology mediated by low affinity multivalent protein-glycan interactions. Curr Opin Chem Biol. 2004; 8(6):617-25. DOI: 10.1016/j.cbpa.2004.10.004. View

19.

Ichiyoshi H, Kiyozuka Y, Kishimoto Y, Fukuhara S, Tsubura A . Massive telomere loss and telomerase RNA expression in dexamethasone-induced apoptosis in mouse thymocytes. Exp Mol Pathol. 2003; 75(2):178-86. DOI: 10.1016/s0014-4800(03)00050-9. View

20.

Smith B, Akers W, Leevy W, Lampkins A, Xiao S, Wolter W . Optical imaging of mammary and prostate tumors in living animals using a synthetic near infrared zinc(II)-dipicolylamine probe for anionic cell surfaces. J Am Chem Soc. 2009; 132(1):67-9. PMC: 2805267. DOI: 10.1021/ja908467y. View