Near-Infrared-Responsive Rare Earth Nanoparticles for Optical Imaging and Wireless Phototherapy

Abstract

Near-infrared (NIR) light is well-suited for the optical imaging and wireless phototherapy of malignant diseases because of its deep tissue penetration, low autofluorescence, weak tissue scattering, and non-invasiveness. Rare earth nanoparticles (RENPs) are promising NIR-responsive materials, owing to their excellent physical and chemical properties. The 4f electron subshell of lanthanides, the main group of rare earth elements, has rich energy-level structures. This facilitates broad-spectrum light-to-light conversion and the conversion of light to other forms of energy, such as thermal and chemical energies. In addition, the abundant loadable and modifiable sites on the surface offer favorable conditions for the functional expansion of RENPs. In this review, the authors systematically discuss the main processes and mechanisms underlying the response of RENPs to NIR light and summarize recent advances in their applications in optical imaging, photothermal therapy, photodynamic therapy, photoimmunotherapy, optogenetics, and light-responsive drug release. Finally, the challenges and opportunities for the application of RENPs in optical imaging and wireless phototherapy under NIR activation are considered.

Keywords: near-infrared light; optical imaging; photoconversion; phototherapy; rare earth nanoparticles.

Figure 1

Periodic table of elements and scattering of different wavelengths of light. a) Location of rare earth elements in the periodic table (blue rectangle). b) Scattering coefficients of different biological tissues and Intralipid scattering tissue phantom as a function of wavelength in the 400–1700 nm region. c) The effective attenuation coefficients of absorption and scattering from oxygenated blood, deoxygenated blood, skin, and fatty tissues. The latter two exhibit the lowest coefficients in both NIR‐I (pink shaded area) or NIR‐II (grey) windows. Reproduced with permission.^{[ 37 ]} Copyright 2009, Springer Nature. d) Light‐tissue interactions resulting from impinging excitation light (blue), interface reflection (cyan), scattering (green), absorption (black circle with purple cross), and autofluorescence (brown), all of which contribute to the loss of signal (fluorescence, red) and increase of noise. b,d) Reproduced with permission.^{[ 36 ]} Copyright 2017, Springer Nature.

Figure 2

Schematic illustration of possible mechanisms for different kinds of light‐to‐light conversions and PL. a) UCL categories: ESA, ETU, PA, EMU, and CET, b) DSL, c) DCL, and d) PL. Reproduced with permission.^{[ 80 ]} Copyright 2023, Wiley‐VCH.

Figure 3

NIR‐responsive RENPs for optical imaging. a) Bright field, confocal, and superimposed images of live human colonic adenocarcinoma cells (HT29), with UCNPs attached. b) In vivo imaging of rats injected with UCNPs below abdominal skin (left), thigh muscles (middle), or below the skin of the back (right). a,b) Reproduced with permission.^{[ 100 ]} Copyright 2008, Elsevier. c) Real‐time video capture of the biodistribution of intravenously injected downshifting RENPs in hairless mice using the imaging system prototype: ventral (top) and left lateral (middle) views. Nude mice bearing melanoma xenografts were intravenously injected with LDNPs and imaged near surrounding tumor regions before dissection (bottom) from the ventral aspect. Reproduced with permission.^{[ 47 ]} Copyright 2013, Springer Nature. d) Supramolecular recognition‐induced assembly and 980 nm NIR‐regulated disassembly of nanoparticles (top); In vivo assembly of UCNP@Azo (the first injection) and DCNP@β‐CD (the second injection) with improved tumor targeting, two‐staged in‐sequence injection strategy, and 980 nm NIR‐regulated in vivo disassembly with rapid clearance in the liver (bottom). Reproduced with permission.^{[ 112 ]} Copyright 2018, Wiley‐VCH. e) The schematic diagram of NIR‐active upconverting PL nanophosphors (UPLNs) used for long‐time PL imaging (left) and in vivo PL imaging of different treatment groups, namely the macrophages, UPLNs, and UPLN‐loaded macrophages (UPLNs@M) groups, at different times (right). Reproduced with permission.^{[ 120 ]} Copyright 2018, American Chemical Society. f) The bioimaging application of NaLuF₄:Yb³⁺, Tm³⁺@NaGdF₄(¹⁵³Sm). Reproduced with permission.^{[ 122 ]} Copyright 2013, American Chemical Society.

Figure 4

NIR‐Responsive RENPs for PTT and PDT. a) Simplified diagrams illustrating the generation of new CR pathways between Nd³⁺ and PB. Reproduced with permission.^{[ 137 ]} Copyright 2019, Wiley‐VCH. b) Illustrations of CR‐induced 1000 nm NIR emissions heating an aqueous solution. Reproduced under terms of the CC‐BY license.^{[ 32 ]} Copyright 2023, Springer Nature. c) Photochemical process of the photosensitizer. d) Proposed mechanism for ROS generation using Tm³⁺. c,d) Reproduced with permission.^{[ 33 ]} Copyright 2022, American Chemical Society. e) Schematic illustration of magnetically targeted NIR‐II bioimaging and PDT in mice. Reproduced under terms of the CC‐BY license.^{[ 159 ]} Copyright 2023, Wiley‐VCH. f) Schematic illustration of SIRIUS implant for wireless PDT. Reproduced with permission.^{[ 161 ]} Copyright 2023, American Chemical Society. g) Schematic illustration of the proposed direct triplet sensitization process in a NaGdF₄:Nd³⁺‐Ce6 hybrid system. Reproduced with permission.^{[ 167 ]} Copyright 2021, Elsevier.

Figure 5

NIR‐Responsive RENPs for PIT. a) Scheme summarizing the mechanisms of combining NIR‐mediated PDT with CTLA‐4 checkpoint blockade for cancer PIT. Reproduced with permission.^{[ 179 ]} Copyright 2017, American Chemical Society. b) Schematic illustration of fabrication and mechanism of UCMSs‐MC540‐TF vaccines for PIT. Reproduced with permission.^{[ 180 ]} Copyright 2018, Wiley‐VCH. c) Schematic illustration of both fabrication and mechanism of NIR‐triggered antigen‐capturing nanoplatform for PIT. d) Survival curves of different groups of mice bearing orthotopic 4T1 tumors after different treatments (top, n = 6, **p < 0.01 vs control group) and survival rates after 4T1 tumor cell rechallenge in the mice (bottom, n = 4, **p < 0.01 vs control group). Data are expressed as mean ± SD. c,d) Reproduced under terms of the CC‐BY license.^{[ 181 ]} Copyright 2019, Wiley‐VCH.

Figure 6

NIR‐Responsive RENPs for optogenetics. a) In vivo experimental scheme for transcranial NIR stimulation of the VTA in anesthetized mice. Reproduced with permission.^{[ 193 ]} Copyright 2018, The American Association for the Advancement of Science. b) The high‐angle annular dark field scanning transmission electron microscopy image (top‐left) and high‐resolution transmission electron microscopy image (bottom‐left) of the obtained multilayer UCNPs and the corresponding schematic illustration of energy dissipation upconversion process in multilayer UCNPs. Reproduced under terms of the CC‐BY license.^{[ 194 ]} Copyright 2021, Springer Nature. c) Schematic illustration of blood glucose reversibly modulated upconversion nanoprobes and closed‐loop glycemic control. Reproduced with permission.^{[ 196 ]} Copyright 2023, American Chemical Society.

Figure 7

NIR‐Responsive RENPs for controlled drug release. a) Schematic illustration of NIR‐responsive azo‐liposome/UCNPs hybrid vesicles for controlled drug delivery. Reproduced with permission.^{[ 206 ]} Copyright 2016, Wiley‐VCH. b) Schematic illustration of constructing UCL‐driven DNA–azo nanopump and NIR‐responsive drug release in living cells. Reproduced with permission.^{[ 207 ]} Copyright 2019, Wiley‐VCH. c) Schematic illustration of the structure of the ZIF‐8‐based delivery system and working principles of NIR‐responsive protein release. Reproduced with permission.^{[ 215 ]} Copyright 2023, Elsevier.

Figure 8

NIR‐Responsive RENPs for combined phototherapy. a) The structure and a possible mechanism for ROS generation of UCNPs/HOFs. Reproduced with permission.^{[ 220 ]} Copyright 2023, Elsevier. b) Schematic illustration of the generation of cross‐relaxation pathways between Nd³⁺ and AgBiS₂ (left) and the enhanced generation of ROS between Er³⁺ and AgBiS₂ (right). Reproduced with permission.^{[ 223 ]} Copyright 2022, Elsevier. c) The construction of nanodrugs for combined cancer phototherapy and description of the functions of every component. Reproduced with permission.^{[ 229 ]} Copyright 2023, Royal Society of Chemistry.