Tumor‐Exocytosed Exosome/Aggregation‐Induced Emission Luminogen Hybrid Nanovesicles Facilitate Efficient Tumor Penetration and Photodynamic Therapy

Abstract

The development of novel photosensitizing agents with aggregation-induced emission (AIE) properties has fueled significant advances in the field of photodynamic therapy (PDT). An electroporation method was used to prepare tumorexocytosed exosome/AIE luminogen (AIEgen) hybrid nanovesicles (DES) that could facilitate efficient tumor penetration. Dexamethasone was then used to normalize vascular function within the tumor microenvironment (TME) to reduce local hypoxia, therebys ignificantly enhancing the PDT efficacy of DES nanovesicles,a nd allowing them to effectively inhibit tumor growth. The hybridization of AIEgen and biological tumor-exocytosed exosomes was achieved for the first time, and combined with PDT approaches by normalizing the intratumoral vasculature as am eans of reducing local tissue hypoxia. This work highlights anew approach to the design of AIEgen-based PDT systems and underscores the potential clinical value of AIEgens.

Conquering the Hypoxia Limitation for Photodynamic Therapy

“…In addition to hyperthermia, antiangiogenic agents (e.g., gemcitabine, [ 223 ] axitinib, [ 224 ] sunitinib, [ 224 ] and dexamethasone [ 192,225 ] ) or chemotherapeutic drugs (e.g., paclitaxel, [ 226–228 ] cisplatin, [ 193 ] erlotinib [ 229 ] ) have also been utilized to normalize the abnormal structure and function of tumor vasculature. This improves blood perfusion enabling more efficient delivery of O 2 as well as chemotherapeutic drugs.…”

“…[ 225 ] Recently, Zhu et al fabricated an aggregation‐induced emission luminogen (AIEgen)‐based biomimetic PDT system called tumor‐exocytosed exosome/AIEgen hybrid nanovesicles (DES). [ 192 ] In this study, they combined dexamethasone with DES to overcome tumor hypoxia, and provide a combination therapy regimen that enhance the efficacy of PDT ( Figure a). Dexamethasone was utilized as an antiangiogenic agent to normalize the tumor vessels, reduce IFP, and improve the available O 2 supply in the tumor.…”

Recent progress in targeted delivery vectors based on biomimetic nanoparticles

“…mRNA-loading Exo regenerated tumor-suppressor function, reinforced restraint of tumor growth, and prolonged survival time. Besides, tumor-exocytosed Exo conjugated with aggregation-induced emission luminogen (AIEgen) were leveraged to load dexamethasone (DEX) (DEX-Exo@AIEgen), enhancing the efficacy of PDT and alleviate local tissue hypoxia in tumors 154 . Tumor-derived Exo loaded with Dox exhibited the homing ability to donor cells, prolonged retention time in tumor sites, and obvious eradication effect in tumor-bearing mice models 155 .…”

Endogenous mRNA Triggered DNA‐Au Nanomachine for In Situ Imaging and Targeted Multimodal Synergistic Cancer Therapy

“…[9] Forphototherapy strategies,especially photothermal therapy (PTT) and photodynamic therapy (PDT) which can generate hyperthermia and reactive oxygen species (ROS)under laser irradiation, respectively,e ach can lead to the irreversible damage of tumors. [10] Unfortunately,the strong photothermal effect in PTT frequently induces normal tissues damage,while the lack of oxygen in deep tumor tissue often leads to the unsatisfactory effect of PDT.A ll of these are detrimental to selective and effective cancer therapy. [11] More recently,t he multimodal synergistic therapy of cancers has attracted great attention.…”