Aggregation-Induced-Emission Photosensitizer-Loaded Nano-superartificial Dendritic Cells with Directly Presenting Tumor Antigens and Reversed Immunosuppression for Photodynamically Boosted Immunotherapy.
Zhihong SunJie LiuYueying LiXun LinYongli ChuWenting WangShiyun HuangWei LiJin PengChuyao LiuWenbin DengChengming SunGuanjun DengPublished in: Advanced materials (Deerfield Beach, Fla.) (2022)
The success of tumor immunotherapy highlights the potential of harnessing immune system to fight cancer. Activating both native T cells and exhausted T cells is a critical step for generating effective antitumor immunity, which is determined based on the efficient presentation of tumor antigens and costimulatory signals by antigen-presenting cells, as well as immunosuppressive reversal. However, strategies for achieving an efficient antigen presentation process and improving immunosuppressive microenvironment remain unresolved. Here, aggregation-induced-emission (AIE) photosensitizer-loaded nano-superartificial dendritic cells (saDC@Fs-NPs) were developed by coating superartificial dendritic cells membranes from genetically engineered 4T1 tumor cells onto nanoaggregates of AIE photosensitizers. The outer cell membranes of saDC@Fs-NPs were derived from recombinant lentivirus-infected 4T1 tumor cells in which peptide-major histocompatibility complex class I, CD86 and anti-LAG3 antibody were simultaneously anchored. These saDC@Fs-NPs could directly stimulate T-cell activation and reverse T-cell exhaustion for cancer immunotherapy. The inner AIE-active photosensitizers induced immunogenic cell death to activate dendritic cells and enhance T lymphocyte infiltration by photodynamic therapy, promoting the transformation of "cold tumors" into "hot tumors", which further boosted immunotherapy efficiency. This work presents a powerful photoactive and artificial antigen-presenting platform for activating both native T cells and exhausted T cells, as well as facilitating tumor photodynamic immunotherapy. This article is protected by copyright. All rights reserved.
Keyphrases
- dendritic cells
- photodynamic therapy
- immune response
- regulatory t cells
- cell death
- case report
- fluorescence imaging
- drug delivery
- cell cycle arrest
- cancer therapy
- stem cells
- induced apoptosis
- living cells
- fluorescent probe
- drug induced
- mesenchymal stem cells
- cell therapy
- high throughput
- young adults
- risk assessment
- papillary thyroid
- deep learning
- endoplasmic reticulum stress
- lymph node metastasis
- endothelial cells