Immunological Effects of Aggregation-Induced Emission Materials

Wu, Haibo; Huang, Wen; Zhou, Xingyu; Min, Yuanzeng

doi:10.3389/fimmu.2020.575816

Cited by 10 publications

(8 citation statements)

References 61 publications

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“…In order to deliver IDO1 inhibitors to tumors more efficiently, a novel strategy to enhance the upload of epacadostat into tumor sites is required. Given their capacity for controlled and targeted drug release to specific cells, nanomaterials are critical in tumor therapy (42)(43)(44)(45). Lu et al (46)have revealed that INCB24360 delivery via a chlorin-based metal-organic framework achieved positive outcomes using combination photodynamic therapy and IDO1 inhibition.…”

Section: Discussionmentioning

confidence: 99%

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Indoleamine 2,3-Dioxygenase 1 Inhibitor-Loaded Nanosheets Enhance CAR-T Cell Function in Esophageal Squamous Cell Carcinoma

et al. 2021

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In chimeric antigen receptor (CAR)-T cell therapy, the role and mechanism of indoleamine 2, 3 dioxygenase 1 (IDO1) in enhancing antitumor immunity require further study. IDO1 is one of the most important immunosuppressive proteins in esophageal squamous cell carcinoma (ESCC). However, the IDO1 inhibitor, epacadostat, has failed in phase III clinical trials; its limited capacity to inhibit IDO1 expression at tumor sites was regarded as a key reason for clinical failure. In this study, we innovatively loaded the IDO1 inhibitor into hyaluronic acid-modified nanomaterial graphene oxide (HA-GO) and explored its potential efficacy in combination with CAR-T cell therapy. We found that inhibition of the antitumor effect of CAR-T cells in ESCC was dependent on the IDO1 metabolite kynurenine. Kynurenine could suppress CAR-T cell cytokine secretion and cytotoxic activity. Inhibiting IDO1 activity significantly enhanced the antitumor effect of CAR-T cells in vitro and in vivo. Our findings suggested that IDO1 inhibitor-loaded nanosheets could enhance the antitumor effect of CAR-T cells compared with free IDO1 inhibitor. Nanosheet-loading therefore provides a promising approach for improving CAR-T cell therapeutic efficacy in solid tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3-Dioxygenase 1 Inhibitor-Loaded Nanosheets Enhance CAR-T Cell Function in Esophageal Squamous Cell Carcinoma

et al. 2021

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“…[32] Moving forward to the biocompatibility evaluation of AIE-based materials, ADMET properties of solubilized AIE nanomaterials have been extensively investigated. [33] However, the majority of efforts have been devoted to improving the absorption of AIE-based nanomaterials for enhanced diagnostic and therapeutic efficiencies. [34] Imbalanced proteostasis often leads to proteome misfolding and aggregation and causes cellular proteome stress that is invisible to current cell viability and toxicity measurements.…”

Section: Introductionmentioning

confidence: 99%

Interrogating the impact of aggregation‐induced emission nanoparticles on in vitro protein stability, ex vivo protein homeostasis, and in vivo biocompatibility

et al. 2022

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Aggregation-induced emission (AIE) materials offer promising perspectives in disease diagnosis and therapeutics given their unique optical and photochemical properties. A key step toward translational applications for AIE materials is to systematically and vigorously evaluate their biosafety and biocompatibility. While previous studies focus on cellular viability and toxicity, the impact of AIE materials on detailed stress responses manifesting cellular fitness has been less explored. Herein, this work provides the first piece of evidence to support amphiphilic functionalization of AIE nanoparticles minimizes the deterioration on proteome stability and cellular protein homeostasis (proteostasis). To this end, four scaffolds of AIE molecules were prepared, further functionalized into eight nanoparticles with two amphiphilic shells respectively, and characterized for their physicochemical properties. Thermal shift assay quantitatively demonstrates that AIE materials after amphiphilic functionalization into nanoparticles enhance proteome thermodynamic stability and ameliorate proteome aggregation propensity in cellular lysate, echoed by cell viability and fractionation experiments. Intriguingly, poor polydispersity index (PDI) of functionalized nanoparticles exaggerates their retention and aggregation in the cell. Comparative proteomic analysis uncovers that amphiphilic functionalization of AIE materials can minimize the deterioration of cellular protein homeostasis network. Finally, vigorous interrogation of functionalized AIE nanoparticles in mice model reveals the complexity of factors affecting the biocompatibility profiles in vivo, including materials' size, PDI, and treatment frequencies. Overall, amphiphilic functionalization of AIE materials into nanoparticles is necessary to maintain proteome stability and balance cellular protein homeostasis.

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“…26 In Wu's review, they focused on summarizing the immunobiological applications and solutions to potential risks associated with AIE materials, and summarized the latest developments, biological effects and biomedical applications of other nanoimaging materials to provide new ideas and approaches for diagnostic and therapeutic imaging with nanomaterials. 27 There is also a review by Tang et al that summarized recent results in the development of AIE probes for cancer therapeutics and discussed some key examples. 28 Conferring the AIE characteristics to conventional fluorescent probes can effectively solve the problems of conven-tional probes used in detecting enzymes.…”

Section: Introductionmentioning

confidence: 99%