ReviewTwo-photon luminescent metal complexes for bioimaging and cancer phototherapy
Graphical abstract
Introduction
As the simplest nonlinear optical phenomenon, two-photon absorbance (TPA) has attracted a great deal of interest in the past few decades, at both the theoretical and experimental levels [1]. TPA has been applied in various research areas, such as three-dimensional data storage [2], [3], [4], [5], up-converted lasing, optical power limiting [6], [7], [8], materials micro-fabrication [9], [10], photodynamic therapy (PDT) [11], [12], [13], [14] and especially fluorescence microscopy [15], [16], [17], [18], [19], [20]. Fluorescence microscopy has become an essential tool in biology and biomedical sciences and offers a visualization approach to understand life (bioimaging). Since the advent of two-photon fluorescence microscopy (TPM) in 1990 by Webb and co-workers [21], great progress has been made in hardware systems; hence, a wide range of bioimaging studies have been carried out by numerous researchers. Imaging and analysis of the dynamic processes in living cells and tissues are the most common applications of TPM: tracking organelle (mitochondria, lysosomes, vacuoles, etc.) dynamics, visualizing drug delivery, imaging cancer and neural tissue, studying the vasculature, heart, eye and brain, and detecting small molecules among others [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32].
Most of these applications are dependent upon the availability of probes with a large two-photon absorption or an excellent two-photon excited emission (TPE). Therefore, there is now a great demand for the design and synthesis of efficient two-photon dyes. This field has been comprehensively reviewed [33], [34], [35]. However, all of these reviews focus on only organic compounds. Metal complexes possess various advantages over organic compounds [36], [37], [38], [39], [40], and applications of the former as two-photon dyes have been developing rapidly. Here, we provide an overview of two-photon luminescent metal complexes applied as bioimaging dyes and cancer therapeutic agents.
Section snippets
Theory of TPA and TPE
The theory of TPA was first proposed by Maria Goeppert-Mayer, the Nobel Prize winner in Physics in 1963 [33]. In her 1931 doctoral thesis, she postulated that a single molecule might be able to simultaneously absorb two photons and be excited from the electronic ground state to an excited state [41]. The TPA process was first demonstrated experimentally by Kaiser and Garret in 1961 [42].
The TPA cross-section (δ) is an important parameter in the TPA phenomenon that reflects the molecular ability
Advantages of TPA and TPE
As mentioned above, fluorescence microscopy has become an essential tool in biology and the biomedical sciences because it offers a visualization approach to understand life. However, important challenges arise when attempting to visualize fluorescently labeled cells deep within living tissues [44]. One-photon confocal microscopy (OPM), developed in 1980s, provides a partial solution to this and works well for many applications [47], [48], [49], [50]. However, the excitation source of the most
Design and advantages of TPE metal complexes
Two-photon excited emission (TPE) was first observed in 1963 using organic dyes, and therefore a huge number of organic compounds with TPA property have been synthesized as well as structure-property relationships. TPA organic compounds can generally be divided into centrosymmetric chromospheres, dipolar dyes, macro-cycles and dendrimers. Although conformational rigidity and strong Ͽ conjugation is a common feature of all these TPA organic dyes, centrosymmetric chromospheres appear to possess
Hydrogen peroxide (H2O2)
Hydrogen peroxide (H2O2), a key reactive oxygen species (ROS), plays important roles in physiological processes [84]. The disorder of H2O2 regulation, resulting in a bio-condition known as cellular oxidative stress, leads to aging and major diseases, especially neurodegenerative diseases like Alzheimer's and Parkinson's [85], [86]. Although dysfunction in H2O2-concentration regulation causes DNA damage and gene instability, H2O2 has been proven to serve as a secondary messenger in cell
Copper(II) ion
Copper, after iron and zinc, is the third most abundant essential trace element in the human body and plays important roles in many fundamental physiological processes in organisms [158]. The disruption of copper homeostasis can lead to various diseases such as Menkes and Wilson diseases, Alzheimer's disease, familial amyotrophic lateral sclerosis, and prion diseases [159], [160], [161], [162]. Of the two copper ions, only Cu+ can enter the cell. However, the bio-imaging of TPF probes for
Adenosine triphosphate (ATP)
Known as the molecular unit of currency, adenosine triphosphate (ATP) plays a fundamental role in life [184]. ATP carries chemical energy and therefore provides or simply transports energy in cells and tissues, especially during metabolic processes [184], [185]. Because energy is essential for life, ATP is acutely involved in many important physiological activities, such as glycolysis, the Kreb's cycle, protein transportation, cell signaling, and DNA replication [186], [187], [188], [189],
Nucleus
Apart from metal clusters, Pt is often used to enhance the properties of organometallic bio-probes. In 2010, Koo and co-workers reported a cyclometalated platinum(II) complex [Pt(L3)Cl][PF6] (Fig. 4, complex 27b) from a specially designed cyclometalating ligand, HL3 [210]. The TPF probe could produce two-photon-induced luminescence at room temperature upon excitation at 700 nm from a mode-locked Ti:sapphire laser. The two-photon absorption cross-section of the complex 27b was 28.0 GM with
Photodynamic therapy (PDT)
It has been more than 35 years since PDT was developed as a useful tool for cancer, among other applications [239], [240]. PDT agents act as photosensitizing drugs using light and an adequate concentration of molecular oxygen. Due to its fundamental specificity and selectivity, the development of PDT as a therapeutic agent is particularly attractive [240], [241]. PDT harnesses energy from light and damages or destroys target tissue by producing cytotoxic species such as singlet oxygen (1O2). To
Concluding remarks
Due to the advantages of TPM over OPM, there is now a strong demand for the design and synthesis of efficient two-photon dyes. Metal complexes offer many advantages over conventional organic dyes, such as synthetic versatility, easily tuned chemical and photophysical properties, high emission quantum yields, long emission lifetimes, and large Stokes shifts, and have opened up new horizons in biomedicine. In this context, two-photon metal-based fluorescent probes with bioimaging and PDT
Acknowledgements
This work was supported by the 973 Program (Nos. 2014CB845604 and 2015CB856301), the National Science Foundation of China (Nos. 21172273, 21171177, 21471164 and J1103305), and the Program for Changjiang Scholars and Innovative Research Team at the University of China (No. IRT1298).
References (251)
- et al.
Spectrochim. Acta A
(2015) - et al.
Biophys. J.
(2015) - et al.
Exp. Eye Res.
(2015) - et al.
Acc. Chem. Res.
(2009) - et al.
J. Neurosci. Meth.
(2001) - et al.
Res. Immunol.
(1996) - et al.
Biophys. J.
(2001) - et al.
Neuron
(1997) - et al.
Biophys. J.
(2000) - et al.
Dyes Pigments
(2011)
Spectrochim. Acta A
Coord. Chem. Rev.
Curr. Opin. Chem. Biol.
J. Biol. Chem.
Cell. Signal.
Biomaterials
Acc. Chem. Res.
Nature
ACS Appl. Mater. Interfaces
Adv. Mater.
RSC Adv.
J. Am. Chem. Soc.
Angew. Chem. Int. Ed.
J. Phys. Chem. A
J. Org. Chem.
Angew. Chem.
Angew. Chem. Int. Ed.
Adv. Mater.
J. Am. Chem. Soc.
Proc. Natl. Acad. Sci. U. S. A.
Biomed. Opt. Express.
Annu. Rev. Biomed. Eng.
Science
Nat. Biotechnol.
J. Am. Chem. Soc.
J. Am. Chem. Soc.
J. Am. Chem. Soc.
Nat. Meth.
J. Am. Chem. Soc.
J. Mater. Chem. B
Adv. Drug Deliver. Rev.
Microscopy (Tokyo)
Angew. Chem. Int. Ed.
Eur. J. Org. Chem.
Adv. Mater.
Angew. Chem. Int.
Chem. Sci.
ACS Appl. Mater. Interfaces
J. Mater. Chem. B
Cited by (219)
Synthesis and characterization of quinoxaline-based rhenium(I) organometallic compounds: Biological and computational applications
2024, Journal of Molecular StructureQuinoline-based metal complexes: Synthesis and applications
2024, Coordination Chemistry ReviewsThe fabrication strategies of near-infrared absorbing transition metal complexes
2023, Coordination Chemistry Reviews
- 1
These authors contributed equally to this work.