Journal article
Spatial transcriptomics reveals the interplay between cancer and immune cells directed by MXene quantum dots
Nano today, v 56, 102285
Jun 2024
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Nanomedicine plays an essential role in the development of tumor treatment modalities. However, tumors have a complex structure that includes a variety of immune cell types, which, along with tumor cells, comprise the heterogeneous tumor microenvironment (TME). Although nanoparticles that overcome the limitations of other classical therapeutics and navigate heterogeneous biological barriers have been developed, many unknown players within the TME still exist. The role of immune cell populations and signaling pathways in the TME, which can affect the nanoparticle distribution in the tumor or the overall outcome of nanotherapeutic treatments, are poorly described. In this study, we used spatial transcriptomics to determine in situ gene expression and identified immune cells, other than tumor-associated macrophages, that play vital roles following nanoparticle exposure. In this proof-of-concept study, a recently explored type of nanoparticle, Ti3C2Tx MXene quantum dots (MQDs), with a single particle diameter of ≤10 nm, were administered to orthotopic breast cancer model mice. Thanks to their red-emitting fluorescence properties, we could track the distribution of MQDs in the tumor. Whole-transcriptome analysis and immunofluorescence staining suggested that the heterogeneous distribution of MQDs results in different tumor and immune cell responses in situ. We observed a more tumor-suppressive phenotype at tumor regions with high MQD accumulation compared to regions with decreased MQD accumulation or naïve tumors. Based on pathway analysis and cell deconvolution, we also identified other immune cell types altered by MQDs, including B cells and neutrophils. Specifically, the application of MQDs recruited and activated B cells and resulted in neutrophil degranulation and NETosis in vivo. Using spatial transcriptomics technology, we defined the fundamental molecular and cellular changes that occur in situ in the TME following MQD administration. Future spatial omics studies involving different nanoparticles with other material characteristics will help design more effective nanotherapeutics.
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•The heterogeneous distribution of MQDs results in different tumor and immune cell responses in situ.•High MQD accumulation results in a more tumor-suppressive phenotype compared to regions with less MQD accumulation.•Based on pathway analysis and cell deconvolution analysis, we identified the involvement of B cells and neutrophils in the TME after MQD exposure.•Spatial biology can identify fundamental molecular changes that occur in situ in the TME upon nanoparticle administration.
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Details
- Title
- Spatial transcriptomics reveals the interplay between cancer and immune cells directed by MXene quantum dots
- Creators
- Ahmet Ceylan - Ankara UniversityRecep Uyar - Ankara UniversityDogantan Çelik - Ankara UniversityAlireza Rafieerad - St. Boniface HospitalOzge Ozgenç Çinar - Ankara UniversityGökce Yagmur Summak - Ankara UniversityCansu Gurcan - Ankara UniversityLinda Giro - University of PaduaRita Khoueiry - Centre International de Recherche sur le CancerMine Turktas - Gazi UniversityMehmet Altay Unal - Ankara UniversityYury Gogotsi - Drexel UniversityLucia Gemma Delogu - University of PaduaSanjiv Dhingra - St. Boniface HospitalAçelya Yilmazer - Ankara University
- Publication Details
- Nano today, v 56, 102285
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Materials Science and Engineering
- Web of Science ID
- WOS:001239436500001
- Scopus ID
- 2-s2.0-85192092091
- Other Identifier
- 991021876715304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Chemistry, Multidisciplinary
- Materials Science, Multidisciplinary
- Nanoscience & Nanotechnology