Design Strategies for Organelle-selective Fluorescent Probes: Where to Start?

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Date 2025 Jan 23

PMID 39845114

Authors

Samira Husen Alamudi

Yong-An Lee

Affiliations

Soon will be listed here.

Abstract

Monitoring physiological changes within cells is crucial for understanding their biological aspects and pathological activities. Fluorescent probes serve as powerful tools for this purpose, offering advantageous characteristics over genetically encoded probes. While numerous organelle-selective probes have been developed in the past decades, several challenges persist. This review explores the strategies and key factors contributing to the successful rationale design of these probes. We systematically discuss the typical mode of cellular uptake generally adopted by fluorescent probes and provide a detailed examination of the key factors to consider in design rationale from two perspectives: the properties of the target organelle and the physicochemical properties of the probe itself. Additionally, recent examples of organelle-targeted probes are presented, along with a discussion of the current challenges faced by fluorescent probes in the field.

References

Ciaramicoli L, Kim H, Alamudi S, Chang Y . ABCB1 Can Actively Pump-out the Background-Free Tame Fluorescent Probe CO-1 From Live Cells. Chem Asian J. 2022; 17(12):e202200229. DOI: 10.1002/asia.202200229. View

Zhitomirsky B, Farber H, Assaraf Y . LysoTracker and MitoTracker Red are transport substrates of P-glycoprotein: implications for anticancer drug design evading multidrug resistance. J Cell Mol Med. 2018; 22(4):2131-2141. PMC: 5867146. DOI: 10.1111/jcmm.13485. View

Ziegler D, Vindrieux D, Goehrig D, Jaber S, Collin G, Griveau A . Calcium channel ITPR2 and mitochondria-ER contacts promote cellular senescence and aging. Nat Commun. 2021; 12(1):720. PMC: 7851384. DOI: 10.1038/s41467-021-20993-z. View

Liu C, Mei Y, Yang H, Zhang Q, Zheng K, Zhang P . Ratiometric Fluorescent Probe for Real-Time Detection of β-Galactosidase Activity in Lysosomes and Its Application in Drug-Induced Senescence Imaging. Anal Chem. 2024; . DOI: 10.1021/acs.analchem.3c05896. View

Choi N, Lee J, Park E, Lee J, Lee J . Recent Advances in Organelle-Targeted Fluorescent Probes. Molecules. 2021; 26(1). PMC: 7795030. DOI: 10.3390/molecules26010217. View

Dickinson B, Srikun D, Chang C . Mitochondrial-targeted fluorescent probes for reactive oxygen species. Curr Opin Chem Biol. 2009; 14(1):50-6. PMC: 2830890. DOI: 10.1016/j.cbpa.2009.10.014. View

Morris M, Rodriguez-Cruz V, Felmlee M . SLC and ABC Transporters: Expression, Localization, and Species Differences at the Blood-Brain and the Blood-Cerebrospinal Fluid Barriers. AAPS J. 2017; 19(5):1317-1331. PMC: 6467070. DOI: 10.1208/s12248-017-0110-8. View

Lu S, Dai Z, Cui Y, Kong D . Recent Development of Advanced Fluorescent Molecular Probes for Organelle-Targeted Cell Imaging. Biosensors (Basel). 2023; 13(3). PMC: 10046058. DOI: 10.3390/bios13030360. View

Paolo G, Kim T . Linking lipids to Alzheimer's disease: cholesterol and beyond. Nat Rev Neurosci. 2011; 12(5):284-96. PMC: 3321383. DOI: 10.1038/nrn3012. View

10.

Zhang W, Zhang J, Li P, Liu J, Su D, Tang B . Two-photon fluorescence imaging reveals a Golgi apparatus superoxide anion-mediated hepatic ischaemia-reperfusion signalling pathway. Chem Sci. 2019; 10(3):879-883. PMC: 6346286. DOI: 10.1039/c8sc03917h. View

11.

Wang H, Feng Z, Del Signore S, Rodal A, Xu B . Active Probes for Imaging Membrane Dynamics of Live Cells with High Spatial and Temporal Resolution over Extended Time Scales and Areas. J Am Chem Soc. 2018; 140(10):3505-3509. PMC: 5858877. DOI: 10.1021/jacs.7b13307. View

12.

Pramanik S, Das A . Fluorescent probes for imaging bioactive species in subcellular organelles. Chem Commun (Camb). 2021; 57(91):12058-12073. DOI: 10.1039/d1cc04273d. View

13.

Ma Y, Poole K, Goyette J, Gaus K . Introducing Membrane Charge and Membrane Potential to T Cell Signaling. Front Immunol. 2017; 8:1513. PMC: 5684113. DOI: 10.3389/fimmu.2017.01513. View

14.

Horobin R, Stockert J, Rashid-Doubell F . Fluorescent cationic probes for nuclei of living cells: why are they selective? A quantitative structure-activity relations analysis. Histochem Cell Biol. 2006; 126(2):165-75. DOI: 10.1007/s00418-006-0156-7. View

15.

Zielonka J, Joseph J, Sikora A, Hardy M, Ouari O, Vasquez-Vivar J . Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications. Chem Rev. 2017; 117(15):10043-10120. PMC: 5611849. DOI: 10.1021/acs.chemrev.7b00042. View

16.

Nakamura A, Takigawa K, Kurishita Y, Kuwata K, Ishida M, Shimoda Y . Hoechst tagging: a modular strategy to design synthetic fluorescent probes for live-cell nucleus imaging. Chem Commun (Camb). 2014; 50(46):6149-52. DOI: 10.1039/c4cc01753f. View

17.

Lee J, Kim Y, Vendrell M, Chang Y . Diversity-oriented fluorescence library approach for the discovery of sensors and probes. Mol Biosyst. 2009; 5(5):411-21. DOI: 10.1039/b821766c. View

18.

Dias C, Nylandsted J . Plasma membrane integrity in health and disease: significance and therapeutic potential. Cell Discov. 2021; 7(1):4. PMC: 7813858. DOI: 10.1038/s41421-020-00233-2. View

19.

Chakraborty S, Bindra A, Thomas A, Zhao Y, Ajayaghosh A . pH-Assisted multichannel heat shock monitoring in the endoplasmic reticulum with a pyridinium fluorophore. Chem Sci. 2024; 15(28):10851-10857. PMC: 11253182. DOI: 10.1039/d4sc01977f. View

20.

Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouyssegur J . Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol. 2009; 29(10):2570-81. PMC: 2682037. DOI: 10.1128/MCB.00166-09. View