Light-responsive hyaluronic acid nanomicelles co-loaded with an IDO inhibitor focus targeted photoimmunotherapy against "immune cold" cancer. (31st October 2021)

• Record Type: Journal Article
• Authors: Wu, Chunhui; Xu, Jiming; Xie, Zhengxin; Huang, Honglin; Li, Ningxi; Wei, Xiaodan; Li, Tingting; Yang, Hong; Li, Shun; Qin, Xiang; Liu, Yiyao
• Is Part Of: Biomaterials science. Volume 9:Number 23(2021)
• Page Start: 8019
• Page End: 8031
• Publication Date: 2021-10-31
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d1bm01409a
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : This work shows a translatable nanoformulation NLG919@HA-Ce6 for the combined targeted PDT and IDO1 blockade immunotherapy against poorly immunogenic tumors. Abstract : Nanomedicine enabled cancer combination immunotherapy not only sufficiently activates the host immune system, but also reprograms the immunosuppressive microenvironment, representing a new generation approach to treat cancer. Herein, we demonstrated a targeted photo- and immune-active nanoplatform termed NLG919@HA-Ce6 to simultaneously elicit efficient immunogenic cell death (ICD) using the photosensitizer Ce6 and modulate the tryptophan metabolic pathway using an indoleamine 2, 3-dioxygenase (IDO) inhibitor NLG919 for the combined photodynamic therapy (PDT) and checkpoint blockade immunotherapy. Against the triple-negative and poorly immunogenic 4T1 breast cancer model, the stable spherical nanomicelle NLG919@HA-Ce6 selectively killed tumour cells via the toxic singlet oxygen upon laser excitation, thus in situ triggering a potent antitumor immune response, as seen via the obvious CRT exposure, ATP release, dendritic cell maturation, etc . Meanwhile, the IDO1-mediated immunosuppression was effectively reprogrammed to an immunostimulatory phenotype, which was accompanied by an enhanced cytotoxic T cell response as well as reduced Treg infiltration in tumour bed. Ultimately, the 4T1 tumour was synergistically suppressed by NLG919@HA-Ce6 due to the outcome of focused PDT, obvious ICD post PDT and IDO1 blockade. This study suggests the promise of NLG919@HA-Ce6 as an alternative simple, stimulative and targeted nanoagent to enable the whole-body photo-immune therapy against "immune cold" cancer.