{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:12:33Z","timestamp":1772453553907,"version":"3.50.1"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["3A4213230428"],"award-info":[{"award-number":["3A4213230428"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015800","name":"Jilin Province Development and Reform Commission","doi-asserted-by":"publisher","award":["3J1212018428"],"award-info":[{"award-number":["3J1212018428"]}],"id":[{"id":"10.13039\/100015800","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nanobiotechnol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Characterizing the tumor immune microenvironment (TIME) to explore potential therapeutic targets is fundamental to advancing precision tumor immunotherapy. However, the immunosuppressive nature of \u201ccold\u201d tumors, notably prostate cancer, poses a significant barrier to immunotherapy, demanding new approaches to simultaneously reinvigorate anti-tumor immunity and modulate the molecular drivers of immune evasion. Here, we identified VSIG4 as a key regulator of prostate tumor-resident macrophage fate through single-cell sequencing analysis. Meanwhile, a shikonin (Shik)-mediated downregulation of VSIG4 in macrophages is verified, potentially attenuating its immunosuppressive effects. Building on these findings, cytosine guanine dinucleotide (CpG) oligodeoxynucleotide (ODN)-modified manganese (Mn)-Shik metal-polyphenol network nanodrugs (Mn\/Shik@CpG NDs) are designed to reverse the \u201ccold\u201d immune environment of prostate tumor. In this scenario, Mn\/Shik@CpG NDs release monomeric components under the stimulation of acidic and glutathione-rich tumor microenvironment (TME), thus exerting their immunomodulatory effects synergistically. Since the released Shik can induce DNA damage by necroptosis promoting reactive oxygen species production, cGAS-STING signaling pathway is initiated, which further activates interferon production in the TME. In addition, the necroptosis of Shik initiates immunogenic cell death, further activating innate immunity and promoting adaptive immune responses. Mn\n                    <jats:sup>2+<\/jats:sup>\n                    is a cGAS-STING sensitizer, which amplifies the intratumoral interferon response. As an immune adjuvant, CpG ODN effectively promotes the maturation of dendritic cells, as well as the helper T cell differentiation and pro-inflammatory cytokine secretion, thus activating both innate and adaptive immunity. In vivo studies suggest that Shik-mediated VSIG4 downregulation, combined with innate and adaptive immune activation, remodels the TIME to evoke a significant anti-tumor response. Furthermore, transcriptomic analysis of rechallenged tumors indicated this durable protection was driven by a genuine immune memory response, revealing a gene signature of T cell activation and immune reprogramming. Collectively, beyond presenting a novel therapeutic candidate for converting immunologically \u201ccold\u201d tumors into \u201chot\u201d ones, our work validates a data-guided design pipeline, offering a conceptual blueprint to inform the precise engineering of future nanodrugs.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1186\/s12951-026-04062-5","type":"journal-article","created":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T08:23:52Z","timestamp":1769934232000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell sequencing-guided design of synergistic chemo-immunotherapy nanodrugs for cGAS-STING activation in prostate cancer therapy"],"prefix":"10.1186","volume":"24","author":[{"given":"Yu","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaowu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingqi","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianyu","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuchuan","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"4062_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.574939","volume":"10","author":"R Zhu","year":"2020","unstructured":"Zhu R, Tao H, Lin W, Tang L, Hu Y. Identification of an immune-related gene signature based on immunogenomic landscape analysis to predict the prognosis of adult acute myeloid leukemia patients. Front Oncol. 2020;10:574939.","journal-title":"Front Oncol"},{"key":"4062_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02251-3","volume":"9","author":"Y Zhang","year":"2018","unstructured":"Zhang Y, Li N, Suh H, Irvine DJ. Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity. Nat Commun. 2018;9:6.","journal-title":"Nat Commun"},{"key":"4062_CR3","doi-asserted-by":"publisher","first-page":"e003744","DOI":"10.1136\/jitc-2021-003744","volume":"10","author":"AS Trigos","year":"2022","unstructured":"Trigos AS, et al. Tumor immune microenvironment of primary prostate cancer with and without germline mutations in homologous recombination repair genes. J Immunother Cancer. 2022;10:e003744.","journal-title":"J Immunother Cancer"},{"key":"4062_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0758-y","volume":"7","author":"W Mao","year":"2019","unstructured":"Mao W, et al. Immunogenicity of prostate cancer is augmented by BET bromodomain inhibition. J Immunother Cancer. 2019;7:277.","journal-title":"J Immunother Cancer"},{"key":"4062_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216409","volume":"577","author":"Z Liu","year":"2023","unstructured":"Liu Z, et al. cGAS-STING signaling in the tumor microenvironment. Cancer Lett. 2023;577:216409.","journal-title":"Cancer Lett"},{"key":"4062_CR6","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.jacc.2018.05.061","volume":"72","author":"M Yang","year":"2018","unstructured":"Yang M, et al. Deficiency of GATA3-positive macrophages improves cardiac function following myocardial infarction or pressure overload hypertrophy. J Am Coll Cardiol. 2018;72:885\u2013904.","journal-title":"J Am Coll Cardiol"},{"key":"4062_CR7","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14020440","volume":"14","author":"C Martori","year":"2022","unstructured":"Martori C, et al. Macrophages as a therapeutic target in metastatic prostate cancer: a way to overcome immunotherapy resistance? Cancers. 2022;14:440.","journal-title":"Cancers"},{"key":"4062_CR8","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.immuni.2018.03.017","volume":"48","author":"C Wang","year":"2018","unstructured":"Wang C, et al. Manganese increases the sensitivity of the cGAS-STING pathway for double-stranded DNA and is required for the host defense against DNA viruses. Immunity. 2018;48:675-687.e7.","journal-title":"Immunity"},{"key":"4062_CR9","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1038\/s41422-020-00395-4","volume":"30","author":"M Lv","year":"2020","unstructured":"Lv M, et al. Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy. Cell Res. 2020;30:966\u201379.","journal-title":"Cell Res"},{"key":"4062_CR10","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1182\/blood-2018-05-847335","volume":"133","author":"PN Wagner","year":"2019","unstructured":"Wagner PN, et al. Increased Ripk1-mediated bone marrow necroptosis leads to myelodysplasia and bone marrow failure in mice. Blood. 2019;133:107\u201320.","journal-title":"Blood"},{"key":"4062_CR11","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202111670","volume":"32","author":"J Tan","year":"2022","unstructured":"Tan J, Ding B, Teng B, Ma P, Lin J. Understanding structure\u2013function relationships of nanoadjuvants for enhanced cancer vaccine efficacy. Adv Funct Mater. 2022;32:2111670.","journal-title":"Adv Funct Mater"},{"key":"4062_CR12","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10040616","volume":"10","author":"C Li","year":"2022","unstructured":"Li C, et al. The immunomodulatory functions of various CpG oligodeoxynucleotideson CEF cells and H9N2 subtype avian influenza virus vaccination. Vaccines. 2022;10:616.","journal-title":"Vaccines"},{"key":"4062_CR13","doi-asserted-by":"publisher","first-page":"5281","DOI":"10.2147\/IJN.S317626","volume":"16","author":"W Chen","year":"2021","unstructured":"Chen W, et al. CpG-Based nanovaccines for cancer immunotherapy. Int J Nanomed. 2021;16:5281\u201399.","journal-title":"Int J Nanomed"},{"key":"4062_CR14","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.jcis.2023.03.204","volume":"642","author":"X Sun","year":"2023","unstructured":"Sun X, et al. Bimetallic infinite coordination nanopolymers via phototherapy and STING activation for eliciting robust antitumor immunity. J Colloid Interface Sci. 2023;642:691\u2013704.","journal-title":"J Colloid Interface Sci"},{"issue":"1","key":"4062_CR15","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202508753","volume":"13","author":"M Li","year":"2025","unstructured":"Li M. Nanoparticle-modified nanofibers induce ferroptosis and stimulate antitumor immunity for melanoma therapy. Adv Sci. 2025;e08753. https:\/\/doi.org\/10.1002\/advs.202508753.","journal-title":"Adv Sci"},{"key":"4062_CR16","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adn3002","author":"J Li","year":"2024","unstructured":"Li J. Hybrid nanoparticle\u2013mediated simultaneous ROS scavenging and STING activation improve the antitumor immunity of in situ vaccines. Sci Adv. 2024. https:\/\/doi.org\/10.1126\/sciadv.adn3002.","journal-title":"Sci Adv"},{"key":"4062_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36325-2","volume":"14","author":"T Hirz","year":"2023","unstructured":"Hirz T, et al. Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses. Nat Commun. 2023;14:663.","journal-title":"Nat Commun"},{"key":"4062_CR18","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20209620","volume":"17","author":"C Xu","year":"2021","unstructured":"Xu C, et al. Probabilistic harmonization and annotation of single-cell transcriptomics data with deep generative models. Mol Syst Biol. 2021;17:e9620.","journal-title":"Mol Syst Biol"},{"key":"4062_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38333-8","volume":"14","author":"Y Zhang","year":"2023","unstructured":"Zhang Y, et al. MetaTiME integrates single-cell gene expression to characterize the meta-components of the tumor immune microenvironment. Nat Commun. 2023;14:2634.","journal-title":"Nat Commun"},{"key":"4062_CR20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00173","volume":"10","author":"DM Elizondo","year":"2019","unstructured":"Elizondo DM, et al. Allograft inflammatory factor-1 governs hematopoietic stem cell differentiation into cDC1 and monocyte-derived dendritic cells through IRF8 and RelB in vitro. Front Immunol. 2019;10:173.","journal-title":"Front Immunol"},{"key":"4062_CR21","first-page":"2285","volume":"13","author":"C-P Huang","year":"2023","unstructured":"Huang C-P, Lu H-L, Shyr C-R. Anti-tumor activity of intratumoral xenogeneic urothelial cell monotherapy or in combination with chemotherapy in syngeneic murine models of bladder cancer. Am J Cancer Res. 2023;13:2285\u2013306.","journal-title":"Am J Cancer Res"},{"key":"4062_CR22","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.18632\/aging.205439","volume":"16","author":"L Cao","year":"2024","unstructured":"Cao L, et al. Identification and validation of anoikis-related lncRNAs for prognostic significance and immune microenvironment characterization in ovarian cancer. Aging. 2024;16:1463\u201383.","journal-title":"Aging"},{"key":"4062_CR23","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6908","volume":"13","author":"L Zheng","year":"2024","unstructured":"Zheng L, et al. An individualized stemness-related signature to predict prognosis and immunotherapy responses for gastric cancer using single\u2010cell and bulk tissue transcriptomes. Cancer Med. 2024;13:e6908.","journal-title":"Cancer Med"},{"key":"4062_CR24","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1126\/science.1170540","volume":"324","author":"K Liu","year":"2009","unstructured":"Liu K, et al. In vivo analysis of dendritic cell development and homeostasis. Science. 2009;324:392\u20137.","journal-title":"Science"},{"key":"4062_CR25","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1038\/s41587-023-01716-9","volume":"41","author":"S Persad","year":"2023","unstructured":"Persad S, et al. SEACells infers transcriptional and epigenomic cellular states from single-cell genomics data. Nat Biotechnol. 2023;41:1746\u201357.","journal-title":"Nat Biotechnol"},{"key":"4062_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28239-2","volume":"13","author":"H Gao","year":"2022","unstructured":"Gao H, et al. Accumulation of microbial DNAs promotes to islet inflammation and \u03b2 cell abnormalities in obesity in mice. Nat Commun. 2022;13:565.","journal-title":"Nat Commun"},{"key":"4062_CR27","doi-asserted-by":"publisher","first-page":"7902","DOI":"10.4049\/jimmunol.181.11.7902","volume":"181","author":"NN Gorgani","year":"2008","unstructured":"Gorgani NN, et al. Complement receptor of the ig superfamily enhances complement-mediated phagocytosis in a subpopulation of tissue resident macrophages. J Immunol. 2008;181:7902\u20138.","journal-title":"J Immunol"},{"key":"4062_CR28","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29540","author":"X Yuan","year":"2017","unstructured":"Yuan X, Yang B-H, Dong Y, Yamamura A, Fu W. CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells. eLife. 2017. https:\/\/doi.org\/10.7554\/eLife.29540.","journal-title":"eLife"},{"key":"4062_CR29","doi-asserted-by":"publisher","first-page":"4041","DOI":"10.1016\/j.molimm.2008.07.011","volume":"45","author":"JQ He","year":"2008","unstructured":"He JQ, Wiesmann C, Van Lookeren Campagne M. A role of macrophage complement receptor CRIg in immune clearance and inflammation. Mol Immunol. 2008;45:4041\u20137.","journal-title":"Mol Immunol"},{"key":"4062_CR30","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1158\/1541-7786.MCR-18-0522","volume":"17","author":"D Bianchi-Frias","year":"2019","unstructured":"Bianchi-Frias D, et al. The aged microenvironment influences the tumorigenic potential of malignant prostate epithelial cells. Mol Cancer Res. 2019;17:321\u201331.","journal-title":"Mol Cancer Res"},{"key":"4062_CR31","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70340","volume":"15","author":"J Liu","year":"2025","unstructured":"Liu J, et al. VSIG4 promotes tumour-associated macrophage M2 polarization and immune escape in colorectal cancer via fatty acid oxidation pathway. Clin Transl Med. 2025;15:e70340.","journal-title":"Clin Transl Med"},{"key":"4062_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109955","volume":"37","author":"L He","year":"2021","unstructured":"He L, et al. Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors. Cell Rep. 2021;37:109955.","journal-title":"Cell Rep"},{"key":"4062_CR33","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.3390\/nu15071797","volume":"15","author":"U-H Park","year":"2023","unstructured":"Park U-H, Youn H, Kim E-J, Um S-J. Shikonin binds and represses PPAR\u03b3 activity by releasing coactivators and modulating histone methylation codes. Nutrients. 2023;15:1797.","journal-title":"Nutrients"},{"key":"4062_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110401","volume":"121","author":"L Yuan","year":"2023","unstructured":"Yuan L, et al. Shikonin inhibits immune checkpoint PD-L1 expression on macrophage in sepsis by modulating PKM2. Int Immunopharmacol. 2023;121:110401.","journal-title":"Int Immunopharmacol"},{"key":"4062_CR35","doi-asserted-by":"publisher","first-page":"18227","DOI":"10.1021\/acsnano.3c05229","volume":"17","author":"W Xu","year":"2023","unstructured":"Xu W, et al. \u201cReaction\u201d-like shaping of self-delivery supramolecular nanodrugs in the nanoprecipitation process. ACS Nano. 2023;17:18227\u201339.","journal-title":"ACS Nano"},{"key":"4062_CR36","doi-asserted-by":"publisher","DOI":"10.3390\/ma15186476","volume":"15","author":"Z Wang","year":"2022","unstructured":"Wang Z, et al. Charge-convertible and reduction-sensitive cholesterol-containing amphiphilic copolymers for improved doxorubicin delivery. Materials. 2022;15:6476.","journal-title":"Materials"},{"key":"4062_CR37","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27144408","volume":"27","author":"L Li","year":"2022","unstructured":"Li L, et al. Mechanism study on nanoparticle negative surface charge modification by ascorbyl palmitate and its improvement of tumor targeting ability. Molecules. 2022;27:4408.","journal-title":"Molecules"},{"key":"4062_CR38","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15030790","volume":"15","author":"D Stavroulaki","year":"2023","unstructured":"Stavroulaki D, et al. Influence of the topology of poly(L-cysteine) on the self-assembly, encapsulation and release profile of doxorubicin on dual-responsive hybrid polypeptides. Pharmaceutics. 2023;15:790.","journal-title":"Pharmaceutics"},{"key":"4062_CR39","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15041159","volume":"15","author":"S Yadav","year":"2023","unstructured":"Yadav S, et al. Redox-responsive comparison of diselenide and disulfide core-cross-linked micelles for drug delivery application. Pharmaceutics. 2023;15:1159.","journal-title":"Pharmaceutics"},{"key":"4062_CR40","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1021\/acs.accounts.0c00150","volume":"53","author":"J Zhou","year":"2020","unstructured":"Zhou J, et al. Polyphenol-mediated assembly for particle engineering. Acc Chem Res. 2020;53:1269\u201378.","journal-title":"Acc Chem Res"},{"key":"4062_CR41","doi-asserted-by":"publisher","first-page":"243","DOI":"10.7150\/jca.65297","volume":"13","author":"H Qi","year":"2022","unstructured":"Qi H, et al. Shikonin induced apoptosis mediated by endoplasmic reticulum stress in colorectal cancer cells. J Cancer. 2022;13:243\u201352.","journal-title":"J Cancer"},{"key":"4062_CR42","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10111831","volume":"10","author":"M-F Tsai","year":"2021","unstructured":"Tsai M-F, et al. Shikonin induced program cell death through generation of reactive oxygen species in renal cancer cells. Antioxidants. 2021;10:1831.","journal-title":"Antioxidants"},{"key":"4062_CR43","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.5591","author":"H Wang","year":"2017","unstructured":"Wang H, et al. Shikonin causes apoptosis by disrupting intracellular calcium homeostasis and mitochondrial function in human hepatoma cells. Exp Ther Med. 2017. https:\/\/doi.org\/10.3892\/etm.2017.5591.","journal-title":"Exp Ther Med"},{"key":"4062_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.119379","volume":"219","author":"Z Zhao","year":"2019","unstructured":"Zhao Z, et al. Interfacial engineered gadolinium oxide nanoparticles for magnetic resonance imaging guided microenvironment-mediated synergetic chemodynamic\/photothermal therapy. Biomaterials. 2019;219:119379.","journal-title":"Biomaterials"},{"key":"4062_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120609","volume":"269","author":"H Wang","year":"2021","unstructured":"Wang H, et al. Tumor-permeated bioinspired theranostic nanovehicle remodels tumor immunosuppression for cancer therapy. Biomaterials. 2021;269:120609.","journal-title":"Biomaterials"},{"key":"4062_CR46","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14163851","volume":"14","author":"R Soler-Agesta","year":"2022","unstructured":"Soler-Agesta R, et al. PT-112 induces mitochondrial stress and immunogenic cell death, targeting tumor cells with mitochondrial deficiencies. Cancers. 2022;14:3851.","journal-title":"Cancers"},{"key":"4062_CR47","doi-asserted-by":"publisher","first-page":"560","DOI":"10.3390\/antiox12030560","volume":"12","author":"J-G Kim","year":"2023","unstructured":"Kim J-G, Kang I, Ahn C-S, Sohn W-M, Kong Y. Omega-class glutathione transferases protect DNA from oxidative stress in pathogenic helminth reproductive cells. Antioxidants. 2023;12:560.","journal-title":"Antioxidants"},{"key":"4062_CR48","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/s41586-019-1000-2","volume":"567","author":"C Zhang","year":"2019","unstructured":"Zhang C, et al. Structural basis of STING binding with and phosphorylation by TBK1. Nature. 2019;567:394\u20138.","journal-title":"Nature"},{"key":"4062_CR49","doi-asserted-by":"publisher","first-page":"3263","DOI":"10.1182\/blood.V99.9.3263","volume":"99","author":"M Montoya","year":"2002","unstructured":"Montoya M, et al. Type i interferons produced by dendritic cells promote their phenotypic and functional activation. Blood. 2002;99:3263\u201371.","journal-title":"Blood"},{"key":"4062_CR50","doi-asserted-by":"publisher","first-page":"6323","DOI":"10.1021\/acs.molpharmaceut.4c00841","volume":"21","author":"H Gong","year":"2024","unstructured":"Gong H, et al. Glatiramer acetate complexes CpG oligodeoxynucleotides into nanoparticles and boosts their TLR9-driven immunity. Mol Pharm. 2024;21:6323\u201338.","journal-title":"Mol Pharm"},{"key":"4062_CR51","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.jconrel.2020.12.004","volume":"330","author":"AB Mirkasymov","year":"2021","unstructured":"Mirkasymov AB, Zelepukin IV, Nikitin PI, Nikitin MP, Deyev SM. In vivo blockade of mononuclear phagocyte system with solid nanoparticles: efficiency and affecting factors. J Control Release. 2021;330:111\u20138.","journal-title":"J Control Release"},{"key":"4062_CR52","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41578-021-00413-w","volume":"7","author":"MMT Van Leent","year":"2022","unstructured":"Van Leent MMT, et al. Regulating trained immunity with nanomedicine. Nat Rev Mater. 2022;7:465\u201381.","journal-title":"Nat Rev Mater"},{"key":"4062_CR53","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-015-0172-9","volume":"22","author":"C Fan","year":"2015","unstructured":"Fan C, Xie Y, Dong Y, Su Y, Upton Z. Investigating the potential of shikonin as a novel hypertrophic scar treatment. J Biomed Sci. 2015;22:70.","journal-title":"J Biomed Sci"},{"key":"4062_CR54","doi-asserted-by":"publisher","DOI":"10.1177\/03946320231161174","volume":"37","author":"Y-B Feng","year":"2023","unstructured":"Feng Y-B, et al. Immunopotentiation effects of apigenin on NK cell proliferation and killing pancreatic cancer cells. Int J Immunopathol Pharmacol. 2023;37:03946320231161174.","journal-title":"Int J Immunopathol Pharmacol"},{"key":"4062_CR55","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-023-00631-z","volume":"8","author":"T Laeremans","year":"2023","unstructured":"Laeremans T, et al. Autologous dendritic cell vaccination against HIV-1 induces changes in natural killer cell phenotype and functionality. Npj Vaccines. 2023;8:29.","journal-title":"Npj Vaccines"},{"key":"4062_CR56","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/s41577-018-0088-1","volume":"19","author":"SC Eisenbarth","year":"2019","unstructured":"Eisenbarth SC. Dendritic cell subsets in T cell programming: location dictates function. Nat Rev Immunol. 2019;19:89\u2013103.","journal-title":"Nat Rev Immunol"},{"key":"4062_CR57","doi-asserted-by":"publisher","first-page":"5066","DOI":"10.1002\/cam4.1730","volume":"7","author":"M Tsiatas","year":"2018","unstructured":"Tsiatas M, et al. Evaluation of the prognostic value of CD3, CD8, and FOXP3 mRNA expression in early-stage breast cancer patients treated with anthracycline\u2010based adjuvant chemotherapy. Cancer Med. 2018;7:5066\u201382.","journal-title":"Cancer Med"},{"key":"4062_CR58","doi-asserted-by":"publisher","unstructured":"Vohra M, Lanjewar A, Upadhyay P, Jadhav U, Ghewade B. Metastatic prostatic adenocarcinoma masquerading as pulmonary tuberculosis: a case report. Cureus. 2022(4). https:\/\/doi.org\/10.7759\/cureus.24104.","DOI":"10.7759\/cureus.24104"},{"key":"4062_CR59","doi-asserted-by":"publisher","unstructured":"Tian H, et al. The pro-cancer and immunosuppressive activity of macrophage-transformed cancer-associated fibroblasts in oral squamous cell carcinoma. J Adv Res. 2025;S209012322500551X. https:\/\/doi.org\/10.1016\/j.jare.2025.07.027.","DOI":"10.1016\/j.jare.2025.07.027"},{"key":"4062_CR60","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50194-3","volume":"15","author":"Z Zeng","year":"2024","unstructured":"Zeng Z, et al. Omicverse: a framework for bridging and deepening insights across bulk and single-cell sequencing. Nat Commun. 2024;15:5983.","journal-title":"Nat Commun"},{"key":"4062_CR61","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cels.2018.11.005","volume":"8","author":"SL Wolock","year":"2019","unstructured":"Wolock SL, Lopez R, Klein AM. Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Syst. 2019;8:281-291.e9.","journal-title":"Cell Syst"}],"container-title":["Journal of Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12951-026-04062-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-026-04062-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-026-04062-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T11:46:06Z","timestamp":1772451966000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12951-026-04062-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,1]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4062"],"URL":"https:\/\/doi.org\/10.1186\/s12951-026-04062-5","relation":{},"ISSN":["1477-3155"],"issn-type":[{"value":"1477-3155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,1]]},"assertion":[{"value":"8 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The Animal Ethics Committee of the First Hospital of Jilin University approved the study protocol (Approval Number: JDYY20250648). All procedures strictly adhered to the principles delineated in the Declaration of \u201cGuiding Principles in the Care and Use of Animals\u201d (China).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have approved the manuscript and agree for the submission.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"198"}}