Organic persistent luminescence imaging for biomedical applications

Abstract

Persistent luminescence is a unique visual phenomenon that occurs after cessation of excitation light irradiation or following oxidization of luminescent molecules. The energy stored within the molecule is released in a delayed manner, resulting in luminescence that can be maintained for seconds, minutes, hours, or even days. Organic persistent luminescence materials (OPLMs) are highly robust and their facile modification and assembly into biocompatible nanostructures makes them attractive tools for in vivo bioimaging, whilst offering an alternative to conventional fluorescence imaging materials for biomedical applications. In this review, we give attention to the existing limitations of each class of OPLM-based molecular bioimaging probes based on their luminescence mechanisms, and how recent research progress has driven efforts to circumvent their shortcomings. We discuss the multifunctionality-focused design strategies, and the broad biological application prospects of these molecular probes. Furthermore, we provide insights into the next generation of OPLMs being developed for bioimaging techniques.

Keywords: Bioimaging; Biomedical application; Molecular probe; Organic persistent luminescence.

Graphical abstract

Fig. 1

(A) Schematic of HNP-based detection of H₂O₂ overproducing diseases. In vivo imaging of (B) PC3 cancer cell line induced tumor mouse models, (C) lipopolysaccharide induced inflammation mouse models, and (D) collagen-induced arthritis mouse models [46].

Fig. 2

(A) Schematic illustration of the CL nanoprobe preparation by nanoprecipitation and the final chemical structure of PCLA-O₂^·−. (B) CL imaging and quantification of emission intensities resulting from LPS induction of O₂^·− production, in the presence or absence of the O₂^·− scavenger Tiron. (C) CL imaging of ultra-low O₂^·− concentrations in mouse tumor models [49].

Fig. 3

(A) Schematic illustration of the preparation method for NIR-II CLS, which emit CL light in the presence of H₂O₂. (B) Results of NIR-II CLS versus fluorescence detection of inflammatory neutrophil imaging in lymph nodes and arthrosis models [64].

Fig. 4

(A) Chemical schematic of Ppa formation. (B) Chemical structures of Ppa-FFGYSA and Ppa-YSA that self-assemble to form supramolecular β-sheets and random coil nanomodules, respectively. (C) Fluorescence (FL) and persistent luminescence (PL) in isolated livers. (D) Schematic explanation of reactivated persistent luminescence of Ppa-FFGYSA and intratumoural injection. (E) Representative FL and PL images of guided orthotopic breast tumor resection before and after surgery [71].

Fig. 5

(A) Synthesis of SPNs and biothiol-activated SPNs with AL imaging in drug-challenged hepatotoxicity mouse models [75]. (B) Synthesis of PPV-TPP SPNs and fluorescence versus AL imaging in peritoneal metastatic tumors, 4 ​h after injection of SPN2.5 [76]. (C) Synthetic routes of SPPVN and PPVP and fluorescence versus AL imaging in peritoneal metastatic tumors, 1.5 ​h after injection of SPPVN [77].

Fig. 6

(A) The mechanisms of AL and design of ALNPs consisting of AL initiator, substrate, and relay unit. (B) Representative ALNPs demonstrating and AL and NIR fluorescence imaging at the different time points in 4T1 tumor-bearing mice [78].

Fig. 7

(A) Design and proposed mechanism of APtN for cancer theranostics. (B) NIR fluorescence imaging and comparisons to AL imaging of 4T1 tumor-bearing mice, imaged 24 ​h after intravenous injection of APtN [79].

Fig. 8

(A) Schematic illustration of red RTP excitation by mobile phone flashlight and chemical structures of the DTBT linear and branched derivatives. (B) Photophysical properties of luminogens s-DTBT , d-DTBT , and t-DTBT. Sunlight excitation of RTP bioimaging in the (C) subcutaneous tissue and (D) lymph nodes of mice. Mobile phone flashlight excitation of RTP bioimaging in (E) subcutaneous tissue and (F) lymph nodes of mice (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 9

(A) Chemical structures of organic semiconductors utilized, and schematic illustration of the differential preparation methods for OSNs-T and OSNs-B. (B) Schematic illustration and ultralong RTP and fluorescence imaging of a mice injected with the subcutaneous inclusions of OSNs. (C) Ultralong phosphorescence and fluorescence imaging of lymph node in living mice [101].

Fig. 10

(A) The molecular structures of the six CS RTP compounds. (B) The phosphorescence spectra and corresponding time-resolved decay curves for the six CS RTP compounds. (C) The influence of π–π interactions on the electron redistribution and RTP behavior. (D) In vivo real-time excitation-free phosphorescent imaging of lymph nodes following intracutaneous injection [102].

Fig. 11

(A) Chemical structures and corresponding scanning electron microscope (SEM) images of CBA crystals. (B) Time-resolved phosphorescence imaging of a mouse and lymph node and different organs [105].

Fig. 12

(A) The molecular design strategy for the AIP compounds. (B) UV absorption spectra and phosphorescence spectra of TPM and TPM-Cl crystalline nanoparticles. (C) Images of HeLa cells at different time-points. (D)In vivo RTP imaging of the developed AIP following subcutaneous injection of TPM. [106].