Recent progress in upconversion nanomaterials for emerging optical biological applications
Graphical abstract
Introduction
Since the beginning of the 21st century, research on upconversion nanoparticles (UCNPs) has rapidly developed in theoretical and applied fields [1], [2]. The photonic upconversion phenomenon was first observed experimentally in the 1960s by Francois Azuel, who showed that low-energy infrared light could be emitted at visible wavelengths in Yb-Er and Er-Tm systems after an intersystem energy transfer, suggesting the existence of excited-state charge transfer between two excited ions in transition metal lattices doped with rare earth metals [3], [4]. In 1972, Menyuk et al. achieved a Yb/Er-doped fluoride lattice, which was the first example of the effective doping of lanthanides [5]. The multiple f-energy levels of rare-earth particles provide multiple leap pathways for their upconversion processes in the luminescence process. Rare earth particles absorb photon energy to produce luminescence through Förster resonance energy transfer (FRET) or Dexter energy transfer (DET) processes that transfer energy to the activator [6], [7].
For the need for diagnostic imaging of diseases in research and fluorescent probes in organisms, a variety of probes and reagents have been developed, such as organic dyes [8], organically modified silica [9], [10], fluorescent proteins [11], [12], [13], metal complexes [14], [15], [16], and semiconductor quantum dots [17]. However, conventional agents usually have many limitations: high-energy short-wavelength excitation with low penetration depth, potential DNA toxicity, autofluorescence, and scattering by fur or skin. Rapid advances in nanotechnology and biotechnology have led to strong interest in the use of UCNPs with excellent optical properties in the biological and medical fields. It is worth mentioning that the application of upconversion nanomaterials in biology has a long history [18], [19]. In the 1999s, Zijlmans et al. were the first to use the upconversion properties of lanthanide-doped phosphors to study biometric events. They used phosphors with antibiotic proteins or antibodies to specifically bind to CD4 membrane antigens of human lymphocytes for visualization [20]. Zhao et al. created a near-infrared (NIR) light-triggered drug release system by loading 7-amino-coumarin derivative-caged anticancer drug chlorambucil in upconversion nanophosphors [21]. And Chatterjee et al. demonstrated a new upconversion fluorophore used for cellular and tissue imaging first [22]. On this basis, upconversion nanomaterials are used in many fields such as upconversion fluorescence imaging, magnetic resonance imaging (MRI), phototherapy [23], optogenetics [24], super-resolution imaging [25], and infrared visual imaging [26]. Upconversion luminescence allows it to be excited in the near-infrared biological window (650–1700 nm) for upconversion luminescence (UCL), which leads to less bioabsorption and deeper penetration properties [27], [28]. In addition, the tunable doping mode and structural morphology of UCNPs bring it targeted narrow-band luminescence and stable physicochemical properties in a wide range of environments. These foundations make UCNPs promising for novel biological applications. Here is a representative event. Indocyanine green (ICG) is a widely used clinical contrast agent, photosensitizer, and photothermal agent. ICG strongly absorbs near-infrared light near 800 nm and generates fluorescence, as well as reactive oxygen species (ROS) and heat. Therefore, ICG is widely used in clinical imaging, photodynamic and photothermal therapy [29], [30], [31], [32]. For well-known reasons, ICG is rapidly cleared after entering the body, easily burst by the body's water-oxygen environment, and not specific [33]. The use of a series of UCNPs-ICG has demonstrated that stable upconversion nanoparticles are a better “partner” for a variety of fluorescent probes [34], [35], [36], [37], [38], [39], [40]. The upconversion immune-nanohybrids (UINBs) developed by Jin's group have the ability to detect prostate cancer cells with a high degree of specificity due to specific non-background and optical stabilization of UCNP properties, as well as colloidal stability and streptavidin (SA)-biotin-driven antibody conjugation [41]. Here, Table 1 lists more comparisons of UCNPs probes and traditional fluorescent probes.
We note that UCNPs have made rapid progress in recent years, which makes it necessary to review the latest advances in time. In this review, we enumerate recent attractive advances in optical-biological aspects of UCNPs, including single-particle imaging, single-cell vesicle imaging, and NIR visualization. In addition, we review recent advances in the therapeutic and diagnostic aspects of UCNPs. Finally, we summarize the prospects and challenges of UCNPs, hoping to bring inspiration to reveal more mechanisms in biological imaging and therapy by presenting the applications of UCNPs from multiple perspectives (Scheme 1).
Section snippets
Upconversion mechanisms
In general, upconversion is a process in which two or more photons are absorbed and light shorter than the excitation wavelength is emitted [50], [51]. Upconversion, or anti-Stokes emission processes, may occur in organic or inorganic materials through different mechanisms. The mechanisms of some typical upconversion processes are listed in Table 2, together with the relevant applications. It has been found that coupled lanthanide f electrons and transition metal d electrons may rather easily
UCNPs-guided imaging and detection
Due to the stable luminescence and strong cross-reactivity of UCNPs, a variety of physicochemical data can be reflected by UCNPs, and Sun's group has synthesized a humidity-sensitive material using a lanthanide-doped metal–organic framework (Y/Yb/Er-MOF), which is expected to be used in humidity sensors [87]. In addition, UCNPs have more accurate imaging, deeper imaging depth, and sharper display than ordinary contrast agents, which helps improve various imaging modalities. Here, we list some
UCNPs-guided therapy
Due to the controllability, precision, and penetration of the laser beam, there is a lot of research dedicated to the development of photo-mediated therapies, such as phototherapy [117], optogenetics [118], optical DNA editing [119], etc. For example, photo-activated antimicrobial strategies have been developed to combat the misuse of antibiotics [120], [121], and light-curing and wound treatment using ultraviolet (UV) or blue light also have been used extensively in clinical practice [122],
Summary and outlook
Upconversion nanoparticles have been paid attention increasingly for their unique advantages, hence we covered recent developments about the upconversion nanoparticles for emerging optical biological applications. We briefly describe the luminescence mechanism including organic and inorganic upconversion materials, while the main part of the review is used to review the applications of upconversion in medicine and biology. Despite more than a decade of scientific and applied research
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This work is financially supported by National Natural Science Foundation of China (Grant No. NSFC 51720105015, 51929201, 51922097, 51772124, 51872282, 52102354 and 52102180), Postdoctoral Innovative Talents Support Program (BX2021360), Project funded by China Postdoctoral Science Foundation (2021M703130), and the Science and Technology Development Planning Project of Jilin Province (20210402046GH).
Hao Chen was born in Yunnan, China, in 1999. He received his B.S. degree (2020) in Zhejiang University. He is currently pursuing his Ph.D. degree under the guidance of Prof. Ping’an Ma in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences.
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Hao Chen was born in Yunnan, China, in 1999. He received his B.S. degree (2020) in Zhejiang University. He is currently pursuing his Ph.D. degree under the guidance of Prof. Ping’an Ma in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences.
Binbin Ding was born in Anhui, China, in 1991. He received his B.S. degree (2015) in Pharmaceutical Engineering from Hefei University of Technology, and his Ph.D. degree (2020) in Inorganic Chemistry under the guidance of Prof. Jun Lin at Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. After graduation, he became an Assistant Professor in Prof. Jun Lin’s group and was promoted to an Associate Professor in 2022. His current research focuses on the synthesis and bioapplications of nanoadjuvants.
Ping’an Ma was born in Jilin, China, in 1982. He received his B.S. degree in Biology in 2005 at Northeast Normal University, and his Ph.D. degree in Biochemistry in 2010 at Northeast Normal University. After graduation, he became an Assistant Professor in Prof. Jun Lin’s group and was promoted to Professor in 2020. His research focuses on the synthesis and application of multifunctional inorganic nanoparticles for bioapplication, particularly the design and mechanism of platinum-based anticancer drugs.
Jun Lin was born in Changchun, China, in 1966. He received B.S. and M.S. degrees in Jilin University, and a Ph.D. degree in Changchun Institute of Applied Chemistry (1995). His postdoctoral studies were performed at the City University of Hong Kong (1996), Institute of New Materials (Germany, 1997), Virginia Commonwealth University (USA, 1998), and University of New Orleans (USA, 1999). He has been working as a Professor at CIAC since 2000. His research interests include bulk- and nanostructured luminescent materials and multifunctional composite materials, together with their applications in display, lighting, and biomedical fields.