Dynamic Adjust of Non‐Radiative and Radiative Attenuation of AIE Molecules Reinforces NIR‐II Imaging Mediated Photothermal Therapy and Immunotherapy

Abstract

Due to the aggregation-caused quenching effect and near-infrared I poor penetration capabilities of common fluorescent molecules, their applications in visualized imaging and photoactivated treatment are limited. Therefore, new near-infrared II (NIR-II) molecule (named TST), which had the abilities of aggregation-induced emission (AIE) and photothermal therapy are synthesized. Moreover, in order to further improve its fluorescent yield and therapeutic effect, camptothecin prodrug (CPT-S-PEG) and novel immune checkpoint inhibitor AZD4635 are used to co-assemble with TST into nanoparticles for drug delivery. On account of the strong interaction of camptothecin and TST, the intramolecular rotation of TST is limited, thereby inhibiting non-radiation attenuation and promoting fluorescence generation when the nanoparticles are intact. As nanoparticles uptake by cancer cells, redox sensitive CPT-S-PEG is degraded and the nanoparticles disintegrate. The released TST enhances non-radiative attenuation and expedites photothermal conversion because of the removal of the constraint of camptothecin. Furthermore, photothermal therapy induces immunogenic cell death of cancer cells and releases abundant ATP into the tumor microenvironment to recruit immune cells. However, superfluous ATP is converted into immunosuppressive adenosine through the CD39-CD73-A2AR pathway. The AZD4635 released by photothermal disintegration of the nanoparticles just blocks this pathway timely, achieving favorable synergistic effect of photothermal therapy, chemotherapy, and immunotherapy.

Immunogenic Cell Death Activates the Tumor Immune Microenvironment to Boost the Immunotherapy Efficiency

“…[ 144 ] APCs recognize HSPs and present HSPs‐chaperoned peptides to CD8 + T cells, which activate the adaptive immunity. [ 145 ] However, PTT alone cannot be effective in ablating distal and metastasizing tumors due to a short tissue penetration depth of the laser source [ 146 ] and suboptimal immune activation. Currently, the combination of photothermal conversion agents with immunotherapeutic agents, such as anti‐CTLA ‐4 antibodies, [ 147 ] anti‐PD‐1/PD‐L1 antibodies, [ 148 ] IDO inhibitors, and immune adjuvants [ 149 ] can substantially enhance immune stimulation and relieve the immunosuppressive tumor microenvironment (Table 2 ).…”

Prospects of NIR fluorescent nanosensors for green detection of SARS-CoV-2

“…Some AIE luminogens (AIEgens) emit intensely brighter fluorescence after aggregation due to the restriction of the intramolecular motion (RIM) mechanism, but most of these AIEgens were obtained from organic molecules and cannot be dissolved in the aqueous solvent until further modifications. [129] Li et al constructed the organic-solvent-soluble AIEgens into hydrophilic NPs (AIE NPs) by a nanoprecipitation method using amphiphilic copolymers (DSPE-PEG 2000 ) as the doping matrix. [124] The biocompatible matrix enabled the AIE NPs to exhibit excellent dispersibility in aqueous media and a satisfactory blood circulation time due to the surface PEG.…”

A Versatile 980 nm Absorbing Aggregation‐Induced Emission Luminogen for NIR‐II Imaging‐Guided Synergistic Photo‐Immunotherapy Against Advanced Pancreatic Cancer

“…Notably, ingenious integration of diagnostic FLI capability with photo-immunotherapy intervention in a single formulation would evidently be of significance in both research and clinical areas. [34,35] Thanks to the concept of aggregation-induced emission (AIE), coined by Tang et al, this dilemma may be reversed by reason of the propeller-like twisted AIE-active molecules could prevent the widely distributed π-π stacking in return with enhanced fluorescence intensity. [36][37][38] Therefore, exploiting PTAs possessing both NIR-II emission and FLI function could be realized by the elaborate manipulation of AIE agents.…”