Biomimetic Glucan Particles with Aggregation-Induced Emission Characteristics for Noninvasive Monitoring of Transplant Immune Response

Abstract

Real-time monitoring of post-transplant immune response is critical to prolong the survival of grafts. The current gold standard for assessing the immune response to graft is biopsy. However, such a method is invasive and prone to false negative results due to limited tissue size available and the heterogeneity of the rejection site. Herein, we report biomimetic glucan particles with aggregation-induced emission (AIE) characteristics (HBTTPEP/GPs) for real-time noninvasive monitoring of post-transplant immune response. We have found that the positively charged near-infrared AIEgens can effectively aggregate in the confined space of glucan particles (GPs), thereby turning on the fluorescence emission. HBTTPEP/GPs can track macrophages for 7 days without hampering the bioactivity. Oral administration of HBTTPEP/GPs can specially target macrophages by mimicking yeast, which then migrate to the transplant rejection site. The fluorescence emitted from HBTTPEP/GPs correlated well with the infiltration of macrophages and the degree of allograft rejection. Furthermore, a single oral HBTTPEP/GPs dose can dynamically evaluate the therapeutic response to immunosuppressive therapy. Consequently, the biomimetic AIE-active glucan particles can be developed as a promising probe for immune-monitoring in solid organ transplantation.

Bringing Inherent Charges into Aggregation-Induced Emission Research

“…Among various building blocks, TPE and triphenylamine (TPA) are two classes of representative AIE moieties for the construction of charged AIEgens (Figure B). TPE and its derivatives are the most reliable moieties to initiate the AIE effect (even after attachment with a variety of functional groups), which can be seen in a large portion of charged AIEgens. − Notably, although TPE is a weak electron donor, its electron-donating ability can be reinforced by substituting the phenyl rings with electron donors such as alkoxy groups . Being another class of AIE moieties, TPA and its derivatives are intrinsically strong electron donors due to the presence of a lone pair of electrons on the nitrogen atom.…”

“…Charged AIEgens are ideal materials for imaging and diagnosis applications due to their tunable targeting capability, high brightness in aggregates, low background signal, and high resistance to photobleaching, which are barely seen in traditional ACQ dyes. On the one hand, charged AIEgens can be used to monitor complicated cellular processes and reflect key physiological and pathological changes. ,, In a recent study, our group developed a series of pyridinium-containing AIEgens for the selective identification of cancer cells over normal cells, which was favorably achieved because of the differential mitochondrial membrane potential . Besides, during photodynamic therapy (PDT)-induced cell apoptosis, these charged AIEgens could undergo mitochondrion-to-nucleus translocation, enabling in situ monitoring of the PDT effect through real-time fluorescence signals.…”

Noncancerous disease-targeting AIEgens

“…Hence, AIEgen-based probes demonstrate the prospects of applying AIEgens over using traditional methods. Beyond the above-mentioned non-cancer diseases, AIEgens have also been applied to detect other biological processes, such as the detection of human germ cell quality, 153 monitoring transplant immune response, 34 and the detection of damage of BBB. 154 Importantly, the detection and diagnosis of specific diseases are of great interest and AIEgens appear to be more effective tools for disease detection according to the literature.…”

“…[26][27][28] However, although several studies and reviews have focused on the AIEgen-based intelligent detection, imaging, or therapy of cancer, 26,[29][30][31][32] a broad review of their value in noncancerous diseases has so far been lacking. [33][34][35][36][37] In this review, we provide a comprehensive account of the detection, diagnosis, bioimaging and bioimaging-guided treatment of noncancerous diseases based on AIEgens (Scheme 1). This review is divided into four sections based on the classification of noncancerous diseases.…”

Imaging strategies for monitoring the immune response

“…In the design of Xie et al , AIE molecules were encapsulated in glucan nanoparticles to trace the infiltration of macrophages after transplantation. 81 This nanoprobe could be selectively internalized by macrophages via mimicking the intestinal infection behavior of yeast and could be retained in macrophages for a prolonged period. No obvious innate immune response was elicited with this nanoparticle, suggesting that this system was compatible with transplantation.…”