Biosynthetic Dendritic Cell-Exocytosed Aggregation-Induced Emission Nanoparticles for Synergistic Photodynamic Immunotherapy

Abstract

Dendritic cell (DC)-derived small extracellular vesicles (DEVs) are recognized as a highly promising alternative to DC vaccines; however, the clinical testing of DEV-based immunotherapy has shown limited therapeutic efficacy. Herein, we develop a straightforward strategy in which DCs serve as a cell reactor to exocytose high-efficient DEV-mimicking aggregation-induced emission (AIE) nanoparticles (DEV-AIE NPs) at a scaled-up yield for synergistic photodynamic immunotherapy. Exocytosed DEV-AIE NPs inherit not only the immune-modulation proteins from parental DCs, enabling T cell activation, but also the loaded AIE-photosensitizer MBPN-TCyP, inducing superior immunogenic cell death (ICD) by selectively accumulating in the mitochondria of tumor cells. Eventually, DEV-AIE synergistic photodynamic immunotherapy elicits dramatic immune responses and efficient eradication of primary tumors, distant tumors, and tumor metastases. In addition, cancer stem cells (CSCs) in 4T1 and CT26 solid tumors were significantly inhibited by the immune functional DEV-AIE NPs. Our work presents a facile method for the cellular generation of EV-biomimetic NPs and demonstrates that the integration of DEVs and AIE photosensitizers is a powerful direction for the production of clinical anticancer nanovaccines.

AIEgens for synergistic anticancer therapy

“…Wang et al developed a nanosystem, DEV-AIE nanoparticles, which employed DCs as a cell reactor for exocytosis, achieving synergistic effects of PDT-immunotherapy. 64 The DEV-AIE nanoparticles were exocytosed by the biosynthesis of MBPN-TCyP with DCs. The DEV-AIE nanoparticles could trigger T cell activation due to the immune-modulation proteins from parental DCs.…”

Extracellular vesicles as a novel photosensitive drug delivery system for enhanced photodynamic therapy

“…In addition, to move to clinical trials, large scale production of EVs or EV mimetics needs to be considered ( Ou et al, 2021b ). To increase the production yield of EVs for PS delivery, Cao et al (2022) have developed a straightforward strategy in which dendritic cells are used as a cell reactor to exocytose high-efficient DEVs-mimicking AIE nanoparticles (DEVs-AIE). If this cell reactor approach can be applied for large scale production of EVs from various other cell types, EV delivery-based new generation of PSs may get close to clinical trials.…”

Black Phosphorus Nanosheets Grafted with Gold Nanorods and Carbon Nanodots for Synergistic Antitumor Therapy

“…7 Photodynamic therapy (PDT) and photothermal therapy (PTT) are two main strategies applied for phototherapy of cancer. 8,9 PDT mainly utilizes reactive oxygen species (ROS) generated from photosensitizers for the destruction of cancer cells and the disruption of microvascular, which has already been sanctioned by the Food and Drug Administration of America (FDA). 10,11 ROS molecules (e.g., hydrogen peroxide, superoxide, singlet oxygen, and hydroxyl radical) usually have very short life spans and narrow radiuses.…”

“…The goal of cancer therapy is focused on the effective killing of cancer cells, while normal cells are not harmed. , Despite rapid progress in the understanding of conventional surgical procedures, chemotherapy, radiotherapy, and immunotherapy, great challenges still exist including severe toxic effects, high cost, drug resistance, and low response rates. − Phototherapy is also a powerful treatment pattern, which has attracted tremendous interest with the advantages like noninvasive treatments and limited side effects and drug resistance . Photodynamic therapy (PDT) and photothermal therapy (PTT) are two main strategies applied for phototherapy of cancer. , PDT mainly utilizes reactive oxygen species (ROS) generated from photosensitizers for the destruction of cancer cells and the disruption of microvascular, which has already been sanctioned by the Food and Drug Administration of America (FDA). , ROS molecules ( e.g. , hydrogen peroxide, superoxide, singlet oxygen, and hydroxyl radical) usually have very short life spans and narrow radiuses .…”