{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:08:20Z","timestamp":1787004500487,"version":"build-2736575974"},"reference-count":114,"publisher":"Portland Press Ltd.","issue":"02","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>The emergence of immunotherapy has led to the clinical approval of several related drugs. However, their efficacy against solid tumors remains limited. As the hub of immune activation, lymph nodes (LNs) play a critical role in tumor immunotherapy by initiating and amplifying immune responses. Nevertheless, the intricate physiological structure and barriers within LNs, combined with the immunosuppressive microenvironment induced by tumor cells, significantly impede the therapeutic efficacy of immunotherapy. Engineered nanoparticles (NPs) have shown great potential in overcoming these challenges by facilitating targeted drug transport to LNs and directly or indirectly activating T cells. This review systematically examines the structural features of LNs, key factors influencing the targeting efficiency of NPs, and current strategies for remodeling the immunosuppressive microenvironment of LNs. Additionally, it discusses future opportunities for optimizing NPs to enhance tumor immunotherapy, addressing challenges in clinical translation and safety evaluation.<\/jats:p>","DOI":"10.1042\/ebc20253008","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T02:27:22Z","timestamp":1743388042000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Emerging strategies in lymph node-targeted nano-delivery systems for tumor immunotherapy"],"prefix":"10.1042","volume":"69","author":[{"given":"Yaoli","family":"Zhao","sequence":"first","affiliation":[{"name":"1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzi","family":"Tian","sequence":"additional","affiliation":[{"name":"1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tong","sequence":"additional","affiliation":[{"name":"1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangliang","family":"Yang","sequence":"additional","affiliation":[{"name":"1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"},{"name":"2Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"},{"name":"3Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8785-867X","authenticated-orcid":false,"given":"Lu","family":"Gan","sequence":"additional","affiliation":[{"name":"1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"},{"name":"2Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"},{"name":"3Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1255-9798","authenticated-orcid":false,"given":"Tuying","family":"Yong","sequence":"additional","affiliation":[{"name":"1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"},{"name":"2Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"},{"name":"3Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"2025033106242904900_EBC-2025-3008C1","doi-asserted-by":"crossref","first-page":"6702","DOI":"10.1021\/acsnano.4c01050","article-title":"Biologically self-assembled tumor cell-derived cancer nanovaccines as an all-in-one platform for cancer immunotherapy","volume":"18","author":"Liang","year":"2024","journal-title":"ACS Nano"},{"key":"2025033106242904900_EBC-2025-3008C2","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41568-019-0186-9","article-title":"Improving cancer immunotherapy through nanotechnology","volume":"19","author":"Goldberg","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"2025033106242904900_EBC-2025-3008C3","doi-asserted-by":"crossref","first-page":"11070","DOI":"10.1021\/acsnano.3c11464","article-title":"Dual-responsive nanomedicine activates programmed antitumor immunity through targeting lymphatic system","volume":"18","author":"Xiao","year":"2024","journal-title":"ACS Nano"},{"key":"2025033106242904900_EBC-2025-3008C4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of cancer: new dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"2025033106242904900_EBC-2025-3008C5","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41590-020-0635-3","article-title":"Lymph node stromal cells: cartographers of the immune system","volume":"21","author":"Krishnamurty","year":"2020","journal-title":"Nat. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C6","doi-asserted-by":"crossref","first-page":"7657","DOI":"10.1039\/D4CS00421C","article-title":"Lymphoid organ-targeted nanomaterials for immunomodulation of cancer, inflammation, and beyond","volume":"53","author":"Hsu","year":"2024","journal-title":"Chem. Soc. Rev."},{"key":"2025033106242904900_EBC-2025-3008C7","article-title":"From structural design to delivery: mRNA therapeutics for cancer immunotherapy.","volume":"4","author":"Zhou","year":"2023","journal-title":"Exploration"},{"key":"2025033106242904900_EBC-2025-3008C8","doi-asserted-by":"crossref","first-page":"106524","DOI":"10.1016\/j.oraloncology.2023.106524","article-title":"Cancer cell-derived extracellular vesicles drive pre-metastatic niche formation of lymph node via IFNGR1\/JAK1\/STAT1-activated-PD-L1 expression on FRCs in head and neck cancer","volume":"145","author":"Han","year":"2023","journal-title":"Oral Oncol."},{"key":"2025033106242904900_EBC-2025-3008C9","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1016\/j.cell.2022.04.019","article-title":"Lymph node colonization induces tumor-immune tolerance to promote distant metastasis","volume":"185","author":"Reticker-Flynn","year":"2022","journal-title":"Cell"},{"key":"2025033106242904900_EBC-2025-3008C10","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1158\/2326-6066.CIR-21-0778","article-title":"Tumor-derived lactic acid modulates activation and metabolic status of draining lymph node stroma","volume":"10","author":"Riedel","year":"2022","journal-title":"Cancer Immunol. Res."},{"key":"2025033106242904900_EBC-2025-3008C11","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.biomaterials.2016.01.006","article-title":"Combinatorial prospects of nano-targeted chemoimmunotherapy","volume":"83","author":"Da Silva","year":"2016","journal-title":"Biomaterials"},{"key":"2025033106242904900_EBC-2025-3008C12","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s44222-022-00010-8","article-title":"Bioinspired nanotopographical design of drug delivery systems","volume":"1","author":"Finbloom","year":"2023","journal-title":"Nat. Rev. Bioeng."},{"key":"2025033106242904900_EBC-2025-3008C13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jconrel.2015.09.062","article-title":"Nanoparticulate immunotherapy for cancer","volume":"219","author":"Kapadia","year":"2015","journal-title":"J. Control. Release"},{"key":"2025033106242904900_EBC-2025-3008C14","article-title":"A review on nano-based drug delivery system for cancer chemoimmunotherapy","volume":"12","author":"Mu","year":"2020","journal-title":"Nanomicro Lett."},{"key":"2025033106242904900_EBC-2025-3008C15","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41577-023-00965-8","article-title":"Same yet different \u2014 how lymph node heterogeneity affects immune responses","volume":"24","author":"Cruz de Casas","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C16","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.it.2012.02.007","article-title":"Lymph node homing of T cells and dendritic cells via afferent lymphatics","volume":"33","author":"F\u00f6rster","year":"2012","journal-title":"Trends Immunol."},{"key":"2025033106242904900_EBC-2025-3008C17","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-10-387","article-title":"Modeling lymphocyte homing and encounters in lymph nodes","volume":"10","author":"Baldazzi","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"2025033106242904900_EBC-2025-3008C18","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/nri1222","article-title":"Homing and cellular traffic in lymph nodes","volume":"3","author":"Andrian","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C19","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1093\/intimm\/dxh113","article-title":"A novel reticular stromal structure in lymph node cortex: an immuno-platform for interactions among dendritic cells, T cells and B cells","volume":"16","author":"Katakai","year":"2004","journal-title":"Int. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C20","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nri3298","article-title":"HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes","volume":"12","author":"Girard","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C21","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s10456-021-09792-8","article-title":"High endothelial venules (HEVs) in immunity, inflammation and cancer","volume":"24","author":"Blanchard","year":"2021","journal-title":"Angiogenesis"},{"key":"2025033106242904900_EBC-2025-3008C22","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.immuni.2006.10.011","article-title":"Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes","volume":"25","author":"Baj\u00e9noff","year":"2006","journal-title":"Immunity"},{"key":"2025033106242904900_EBC-2025-3008C23","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.it.2021.07.003","article-title":"Communication, construction, and fluid control: lymphoid organ fibroblastic reticular cell and conduit networks","volume":"42","author":"Acton","year":"2021","journal-title":"Trends Immunol."},{"key":"2025033106242904900_EBC-2025-3008C24","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1038\/ni1513","article-title":"Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells","volume":"8","author":"Link","year":"2007","journal-title":"Nat. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C25","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.immuni.2014.12.024","article-title":"Strategically localized dendritic cells promote rapid T cell responses to lymph-borne particulate antigens","volume":"42","author":"Gerner","year":"2015","journal-title":"Immunity"},{"key":"2025033106242904900_EBC-2025-3008C26","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.immuni.2008.12.014","article-title":"Conduits mediate transport of low-molecular-weight antigen to lymph node follicles","volume":"30","author":"Roozendaal","year":"2009","journal-title":"Immunity"},{"key":"2025033106242904900_EBC-2025-3008C27","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.immuni.2004.11.013","article-title":"The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node","volume":"22","author":"Sixt","year":"2005","journal-title":"Immunity"},{"key":"2025033106242904900_EBC-2025-3008C28","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.immuni.2007.06.007","article-title":"B cells acquire particulate antigen in a macrophage-rich area at the boundary between the follicle and the subcapsular sinus of the lymph node","volume":"27","author":"Carrasco","year":"2007","journal-title":"Immunity"},{"key":"2025033106242904900_EBC-2025-3008C29","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.semcdb.2014.11.012","article-title":"Lymphatic system: an active pathway for immune protection","volume":"38","author":"Liao","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"2025033106242904900_EBC-2025-3008C30","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/ni.3101","article-title":"The endothelial protein PLVAP in lymphatics controls the entry of lymphocytes and antigens into lymph nodes","volume":"16","author":"Rantakari","year":"2015","journal-title":"Nat. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C31","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/nri2297","article-title":"CCR7 and its ligands: balancing immunity and tolerance","volume":"8","author":"F\u00f6rster","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C32","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1093\/intimm\/dxn110","article-title":"The conduit system of the lymph node","volume":"20","author":"Roozendaal","year":"2008","journal-title":"Int. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C33","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/ni.2889","article-title":"The atypical chemokine receptor CCRL1 shapes functional CCL21 gradients in lymph nodes","volume":"15","author":"Ulvmar","year":"2014","journal-title":"Nat. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C34","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1126\/science.1228456","article-title":"Interstitial dendritic cell guidance by haptotactic chemokine gradients","volume":"339","author":"Weber","year":"2013","journal-title":"Science"},{"key":"2025033106242904900_EBC-2025-3008C35","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.1172\/JCI125740","article-title":"Transcytosis route mediates rapid delivery of intact antibodies to draining lymph nodes","volume":"129","author":"K\u00e4h\u00e4ri","year":"2019","journal-title":"J. Clin. Invest."},{"key":"2025033106242904900_EBC-2025-3008C36","doi-asserted-by":"crossref","DOI":"10.1186\/s40413-014-0047-7","article-title":"Intralymphatic immunotherapy","volume":"8","author":"Senti","year":"2015","journal-title":"World Allergy Organ. J."},{"key":"2025033106242904900_EBC-2025-3008C37","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1158\/0008-5472.CAN-11-2957","article-title":"Preclinical evaluation of TriMix and antigen mRNA-based antitumor therapy","volume":"72","author":"Van Lint","year":"2012","journal-title":"Cancer Res."},{"key":"2025033106242904900_EBC-2025-3008C38","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1021\/acs.accounts.0c00260","article-title":"Engineering strategies for lymph node targeted immune activation","volume":"53","author":"Chen","year":"2020","journal-title":"Acc. Chem. Res."},{"key":"2025033106242904900_EBC-2025-3008C39","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/MOT.0000000000000488","article-title":"Harnessing the lymph node microenvironment","volume":"23","author":"O\u2019Neill","year":"2018","journal-title":"Curr. Opin. Organ Transplant."},{"key":"2025033106242904900_EBC-2025-3008C40","article-title":"Application of nano-delivery systems in lymph nodes for tumor immunotherapy","volume":"15","author":"Xia","year":"2023","journal-title":"Nanomicro Lett."},{"key":"2025033106242904900_EBC-2025-3008C41","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.1016\/j.apsb.2024.06.015","article-title":"Transepithelial transport of nanoparticles in oral drug delivery: from the perspective of surface and holistic property modulation","volume":"14","author":"Zheng","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"2025033106242904900_EBC-2025-3008C42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jconrel.2017.08.009","article-title":"Lymph node targeting strategies to improve vaccination efficacy","volume":"267","author":"Jiang","year":"2017","journal-title":"J. Control. Release"},{"key":"2025033106242904900_EBC-2025-3008C43","doi-asserted-by":"crossref","first-page":"3724","DOI":"10.1002\/adma.201200446","article-title":"Engineering nano- and microparticles to tune immunity","volume":"24","author":"Moon","year":"2012","journal-title":"Adv. Mater. Weinheim"},{"key":"2025033106242904900_EBC-2025-3008C44","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13075-017-1323-z","article-title":"Lymphatic delivery of etanercept via nanotopography improves response to collagen-induced arthritis","volume":"19","author":"Aldrich","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"2025033106242904900_EBC-2025-3008C45","doi-asserted-by":"crossref","first-page":"100740","DOI":"10.1016\/j.ctarc.2023.100740","article-title":"Efficient drug delivery to lymph nodes by intradermal administration and enhancement of anti-tumor effects of immune checkpoint inhibitors","volume":"36","author":"Tanaka","year":"2023","journal-title":"Cancer Treat. Res. Commun."},{"key":"2025033106242904900_EBC-2025-3008C46","doi-asserted-by":"crossref","first-page":"115130","DOI":"10.1016\/j.addr.2023.115130","article-title":"Nanocarriers transport across the gastrointestinal barriers: the contribution to oral bioavailability via blood circulation and lymphatic pathway","volume":"203","author":"Wang","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"2025033106242904900_EBC-2025-3008C47","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nrd4608","article-title":"From sewer to saviour \u2014 targeting the lymphatic system to promote drug exposure and activity","volume":"14","author":"Trevaskis","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"2025033106242904900_EBC-2025-3008C48","article-title":"Intramuscular vaccination targeting mucosal tumor draining lymph node enhances integrins-mediated CD8+ T cell infiltration to control mucosal tumor growth","volume":"7","author":"Qiu","year":"2018","journal-title":"Oncoimmunology"},{"key":"2025033106242904900_EBC-2025-3008C49","doi-asserted-by":"crossref","first-page":"20825","DOI":"10.1021\/acsnano.3c05853","article-title":"Size-dependent in vivo transport of nanoparticles: implications for delivery, targeting, and clearance","volume":"17","author":"Xu","year":"2023","journal-title":"ACS Nano"},{"key":"2025033106242904900_EBC-2025-3008C50","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtn.2023.102083","article-title":"mRNA vaccine trafficking and resulting protein expression after intramuscular administration","volume":"35","author":"Hassett","year":"2024","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"2025033106242904900_EBC-2025-3008C51","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jconrel.2014.04.051","article-title":"Nano-chemotherapeutics: maximising lymphatic drug exposure to improve the treatment of lymph-metastatic cancers","volume":"193","author":"Ryan","year":"2014","journal-title":"J. Control. Release"},{"key":"2025033106242904900_EBC-2025-3008C52","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.coche.2014.11.003","article-title":"Overcoming transport barriers for interstitial-, lymphatic-, and lymph node-targeted drug delivery","volume":"7","author":"Thomas","year":"2015","journal-title":"Curr. Opin. Chem. Eng."},{"key":"2025033106242904900_EBC-2025-3008C53","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.jconrel.2021.01.012","article-title":"The impact of size on particle drainage dynamics and antibody response","volume":"331","author":"Zinkhan","year":"2021","journal-title":"J. Control. Release"},{"key":"2025033106242904900_EBC-2025-3008C54","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s41467-021-27750-2","article-title":"Yeast-derived nanoparticles remodel the immunosuppressive microenvironment in tumor and tumor-draining lymph nodes to suppress tumor growth","volume":"13","author":"Xu","year":"2022","journal-title":"Nat. Commun."},{"key":"2025033106242904900_EBC-2025-3008C55","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1002\/eji.200737984","article-title":"Nanoparticles target distinct dendritic cell populations according to their size","volume":"38","author":"Manolova","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C56","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/s41565-020-0679-4","article-title":"Programmable multistage drug delivery to lymph nodes","volume":"15","author":"Schudel","year":"2020","journal-title":"Nat. Nanotechnol."},{"key":"2025033106242904900_EBC-2025-3008C57","doi-asserted-by":"crossref","DOI":"10.1186\/s12989-017-0199-z","article-title":"Mechanistic understanding of nanoparticles\u2019 interactions with extracellular matrix: the cell and immune system","volume":"14","author":"Engin","year":"2017","journal-title":"Part. Fibre Toxicol."},{"key":"2025033106242904900_EBC-2025-3008C58","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2020.00166","article-title":"Recent advances in understanding the protein corona of nanoparticles and in the formulation of \u201cstealthy\u201d nanomaterials","volume":"8","author":"Rampado","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"2025033106242904900_EBC-2025-3008C59","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.ijpharm.2015.08.060","article-title":"Protein corona hampers targeting potential of MUC1 aptamer functionalized SN-38 core-shell nanoparticles","volume":"494","author":"Varnamkhasti","year":"2015","journal-title":"Int. J. Pharm."},{"key":"2025033106242904900_EBC-2025-3008C60","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1021\/bc049951i","article-title":"Toxicity of gold nanoparticles functionalized with cationic and anionic side chains","volume":"15","author":"Goodman","year":"2004","journal-title":"Bioconjug. Chem."},{"key":"2025033106242904900_EBC-2025-3008C61","doi-asserted-by":"crossref","first-page":"6867","DOI":"10.1016\/j.biomaterials.2010.05.027","article-title":"The systemic toxicity of positively charged lipid nanoparticles and the role of toll-like receptor 4 in immune activation","volume":"31","author":"Kedmi","year":"2010","journal-title":"Biomaterials"},{"key":"2025033106242904900_EBC-2025-3008C62","doi-asserted-by":"crossref","first-page":"2306752","DOI":"10.1002\/adfm.202306752","article-title":"Cationic lipids-mediated dual-targeting of both dendritic cells and tumor cells for potent cancer immunotherapy","volume":"33","author":"Li","year":"2023","journal-title":"Adv. Funct. Mater."},{"key":"2025033106242904900_EBC-2025-3008C63","article-title":"Lymph-targeted high-density lipoprotein-mimetic nanovaccine for multi-antigenic personalized cancer immunotherapy","volume":"10","author":"Liu","year":"2024","journal-title":"Sci. Adv."},{"key":"2025033106242904900_EBC-2025-3008C64","doi-asserted-by":"crossref","first-page":"101068","DOI":"10.1016\/j.mtbio.2024.101068","article-title":"Targeting lymph nodes for enhanced cancer vaccination: from nanotechnology to tissue engineering","volume":"26","author":"Wang","year":"2024","journal-title":"Materials Today Bio"},{"key":"2025033106242904900_EBC-2025-3008C65","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1021\/acs.molpharmaceut.9b01182","article-title":"The effect of size and charge of lipid nanoparticles prepared by microfluidic mixing on their lymph node transitivity and distribution","volume":"17","author":"Nakamura","year":"2020","journal-title":"Mol. Pharm."},{"key":"2025033106242904900_EBC-2025-3008C66","doi-asserted-by":"crossref","first-page":"118841","DOI":"10.1016\/j.ijpharm.2019.118841","article-title":"Stimuli-responsive charge-reversal nano drug delivery system: the promising targeted carriers for tumor therapy","volume":"575","author":"Fang","year":"2020","journal-title":"Int. J. Pharm."},{"key":"2025033106242904900_EBC-2025-3008C67","doi-asserted-by":"crossref","first-page":"9779","DOI":"10.3390\/ijms25189779","article-title":"Charge-reversal nano-drug delivery systems in the tumor microenvironment: mechanisms, challenges, and therapeutic applications","volume":"25","author":"Liang","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"2025033106242904900_EBC-2025-3008C68","doi-asserted-by":"crossref","DOI":"10.1002\/smll.202304713","article-title":"Charge-reversible nanoparticles: advanced delivery systems for therapy and diagnosis","volume":"20","author":"Veider","year":"2024","journal-title":"Small"},{"key":"2025033106242904900_EBC-2025-3008C69","doi-asserted-by":"crossref","first-page":"2301041","DOI":"10.1002\/smll.202301041","article-title":"In situ tumor vaccine for lymph nodes delivery and cancer therapy based on small size nanoadjuvant","volume":"19","author":"Zhang","year":"2023","journal-title":"Small"},{"key":"2025033106242904900_EBC-2025-3008C70","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.colsurfb.2015.10.029","article-title":"Imaging-based analysis of liposome internalization to macrophage cells: effects of liposome size and surface modification with PEG moiety","volume":"136","author":"Lee","year":"2015","journal-title":"Colloids and Surfaces B: Biointerfaces"},{"key":"2025033106242904900_EBC-2025-3008C71","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0378-5173(02)00342-3","article-title":"Improved immune response from biodegradable polymer particles entrapping tetanus toxoid by use of different immunization protocol and adjuvants","volume":"245","author":"Raghuvanshi","year":"2002","journal-title":"Int. J. Pharm."},{"key":"2025033106242904900_EBC-2025-3008C72","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.biomaterials.2005.05.082","article-title":"The effect of methoxy-PEG chain length and molecular architecture on lymph node targeting of immuno-PEG liposomes","volume":"27","author":"Moghimi","year":"2006","journal-title":"Biomaterials"},{"key":"2025033106242904900_EBC-2025-3008C73","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1517\/17425240903085128","article-title":"Drug delivery to the lymphatic system: importance in future cancer diagnosis and therapies","volume":"6","author":"Xie","year":"2009","journal-title":"Expert Opin. Drug Deliv."},{"key":"2025033106242904900_EBC-2025-3008C74","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.1021\/mp300190g","article-title":"Effect of the poly(ethylene glycol) (PEG) density on the access and uptake of particles by antigen-presenting cells (APCs) after subcutaneous administration","volume":"9","author":"Zhan","year":"2012","journal-title":"Mol. Pharm."},{"key":"2025033106242904900_EBC-2025-3008C75","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jconrel.2011.12.017","article-title":"PEGylated cationic liposomes robustly augment vaccine-induced immune responses: role of lymphatic trafficking and biodistribution","volume":"159","author":"Zhuang","year":"2012","journal-title":"J. Control. Release"},{"key":"2025033106242904900_EBC-2025-3008C76","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1002\/anie.201508626","article-title":"Engineering polymer hydrogel nanoparticles for lymph node-targeted delivery","volume":"55","author":"De Koker","year":"2016","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"2025033106242904900_EBC-2025-3008C77","doi-asserted-by":"crossref","first-page":"7410","DOI":"10.1021\/acsnano.9b03924","article-title":"Role of nanoparticle mechanical properties in cancer drug delivery","volume":"13","author":"Hui","year":"2019","journal-title":"ACS Nano"},{"key":"2025033106242904900_EBC-2025-3008C78","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.apsb.2021.03.007","article-title":"Effect of physicochemical properties on in vivo fate of nanoparticle-based cancer immunotherapies","volume":"11","author":"Wang","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"2025033106242904900_EBC-2025-3008C79","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2214757120","article-title":"Nanoparticle elasticity regulates the formation of cell membrane-coated nanoparticles and their nano-bio interactions","volume":"120","author":"Zou","year":"2023","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"2025033106242904900_EBC-2025-3008C80","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202100106","article-title":"Engineering the deformability of albumin-stabilized emulsions for lymph-node vaccine delivery","volume":"33","author":"Song","year":"2021","journal-title":"Adv. Mater. Weinheim"},{"key":"2025033106242904900_EBC-2025-3008C81","doi-asserted-by":"crossref","first-page":"23797","DOI":"10.1021\/acsnano.4c09094","article-title":"Modulating elasticity of liposome for enhanced cancer immunotherapy","volume":"18","author":"Yuan","year":"2024","journal-title":"ACS Nano"},{"key":"2025033106242904900_EBC-2025-3008C82","doi-asserted-by":"crossref","first-page":"25826","DOI":"10.1021\/acsnano.4c09053","article-title":"Glucosylated nanovaccines for dendritic cell-targeted antigen delivery and amplified cancer immunotherapy","volume":"18","author":"Liu","year":"2024","journal-title":"ACS Nano"},{"key":"2025033106242904900_EBC-2025-3008C83","first-page":"345","article-title":"STING-activating dendritic cell-targeted nanovaccines that evoke potent antigen cross-presentation for cancer immunotherapy","volume":"42","author":"Nguyen","year":"2024","journal-title":"Bioact. Mater."},{"key":"2025033106242904900_EBC-2025-3008C84","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.jconrel.2024.07.056","article-title":"Identification of a novel DEC-205 binding peptide to develop dendritic cell-targeting nanovaccine for cancer immunotherapy","volume":"373","author":"Zheng","year":"2024","journal-title":"J. Control. Release"},{"key":"2025033106242904900_EBC-2025-3008C85","doi-asserted-by":"crossref","DOI":"10.1002\/anie.202318515","article-title":"Development of mannosylated lipid nanoparticles for mRNA cancer vaccine with high antigen presentation efficiency and immunomodulatory capability","volume":"63","author":"Lei","year":"2024","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"2025033106242904900_EBC-2025-3008C86","article-title":"Nanobodies outperform antibodies - rapid functionalization with equal in vivo targeting properties","volume":"36","author":"Jung","year":"2024","journal-title":"Adv. Mater. Weinheim"},{"key":"2025033106242904900_EBC-2025-3008C87","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/s41565-022-01134-z","article-title":"Cancer immunotherapy based on image-guided STING activation by nucleotide nanocomplex-decorated ultrasound microbubbles","volume":"17","author":"Li","year":"2022","journal-title":"Nat. Nanotechnol."},{"key":"2025033106242904900_EBC-2025-3008C88","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202006007","article-title":"Development of a cancer vaccine using in vivo click-chemistry-mediated active lymph node accumulation for improved immunotherapy","volume":"33","author":"Qin","year":"2021","journal-title":"Adv. Mater. Weinheim"},{"key":"2025033106242904900_EBC-2025-3008C89","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1126\/science.aaf1328","article-title":"SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions","volume":"352","author":"Pucci","year":"2016","journal-title":"Science"},{"key":"2025033106242904900_EBC-2025-3008C90","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.00347","article-title":"Lymph node subcapsular sinus macrophages as the frontline of lymphatic immune defense","volume":"10","author":"Louie","year":"2019","journal-title":"Front. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C91","doi-asserted-by":"crossref","first-page":"9478","DOI":"10.1021\/acsnano.0c02240","article-title":"Suppressing subcapsular sinus macrophages enhances transport of nanovaccines to lymph node follicles for robust humoral immunity","volume":"14","author":"Zhang","year":"2020","journal-title":"ACS Nano"},{"key":"2025033106242904900_EBC-2025-3008C92","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202409914","article-title":"Transformable gel-to-nanovaccine enhances cancer immunotherapy via metronomic-like immunomodulation and collagen-mediated paracortex delivery","volume":"36","author":"Jin","year":"2024","journal-title":"Adv. Mater. Weinheim"},{"key":"2025033106242904900_EBC-2025-3008C93","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/s41563-024-01825-z","article-title":"Lyophilized lymph nodes for improved delivery of chimeric antigen receptor T cells","volume":"23","author":"Shi","year":"2024","journal-title":"Nat. Mater."},{"key":"2025033106242904900_EBC-2025-3008C94","doi-asserted-by":"crossref","first-page":"116951","DOI":"10.1016\/j.biopha.2024.116951","article-title":"Recent advances in biomimetic cell membrane\u2013camouflaged nanoparticles for cancer therapy","volume":"177","author":"Alimohammadvand","year":"2024","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"2025033106242904900_EBC-2025-3008C95","doi-asserted-by":"crossref","first-page":"6333","DOI":"10.1021\/acsnano.3c11189","article-title":"Antigen self-presented personalized nanovaccines boost the immunotherapy of highly invasive and metastatic tumors","volume":"18","author":"Wang","year":"2024","journal-title":"ACS Nano"},{"key":"2025033106242904900_EBC-2025-3008C96","doi-asserted-by":"crossref","first-page":"102173","DOI":"10.1016\/j.apmt.2024.102173","article-title":"Macrophage membrane-coated eucommia ulmoides polysaccharides-loaded PLGA nanoparticles as an effective antigen-targeted delivery system","volume":"38","author":"Zhang","year":"2024","journal-title":"Applied Materials Today"},{"key":"2025033106242904900_EBC-2025-3008C97","doi-asserted-by":"crossref","first-page":"7878","DOI":"10.1021\/acsami.2c22363","article-title":"Surgically derived cancer cell membrane-coated R837-loaded poly(2-Oxazoline) nanoparticles for prostate cancer immunotherapy","volume":"15","author":"Li","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"2025033106242904900_EBC-2025-3008C98","article-title":"Extracellular vesicles hybrid plasmid-loaded lipid nanovesicles for synergistic cancer immunotherapy","volume":"23","author":"Tong","year":"2023","journal-title":"Mater. Today Bio"},{"key":"2025033106242904900_EBC-2025-3008C99","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.12248","article-title":"Extracellular vesicles engineered to bind albumin demonstrate extended circulation time and lymph node accumulation in mouse models","volume":"11","author":"Liang","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"2025033106242904900_EBC-2025-3008C100","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41571-022-00620-6","article-title":"Clinical relevance of tumour-associated macrophages","volume":"19","author":"Pittet","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"2025033106242904900_EBC-2025-3008C101","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abl3649","article-title":"Albumin nanoparticle containing a PI3K\u03b3 inhibitor and paclitaxel in combination with \u03b1-PD1 induces tumor remission of breast cancer in mice","volume":"14","author":"Song","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"2025033106242904900_EBC-2025-3008C102","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2024.122910","article-title":"A size-switchable nanocluster remodels the immunosuppressive microenvironment of tumor and tumor-draining lymph nodes for improved cancer immunotherapy","volume":"315","author":"Tong","year":"2025","journal-title":"Biomaterials"},{"key":"2025033106242904900_EBC-2025-3008C103","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1038\/s41467-023-38014-6","article-title":"Temperature sensitive liposome based cancer nanomedicine enables tumour lymph node immune microenvironment remodelling","volume":"14","author":"Fu","year":"2023","journal-title":"Nat. Commun."},{"key":"2025033106242904900_EBC-2025-3008C104","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.it.2021.06.006","article-title":"Lymph node fibroblastic reticular cells steer immune responses","volume":"42","author":"Li","year":"2021","journal-title":"Trends Immunol."},{"key":"2025033106242904900_EBC-2025-3008C105","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/imr.12748","article-title":"Fibroblastic reticular cells at the nexus of innate and adaptive immune responses","volume":"289","author":"Perez-Shibayama","year":"2019","journal-title":"Immunol. Rev."},{"key":"2025033106242904900_EBC-2025-3008C106","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1002\/eji.201948368","article-title":"IL-7 derived from lymph node fibroblastic reticular cells is dispensable for naive T cell homeostasis but crucial for central memory T cell survival","volume":"50","author":"Knop","year":"2020","journal-title":"Eur. J. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C107","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0027618","article-title":"Fibroblastic reticular cells from lymph nodes attenuate T cell expansion by producing nitric oxide","volume":"6","author":"Siegert","year":"2011","journal-title":"PLoS ONE"},{"key":"2025033106242904900_EBC-2025-3008C108","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/s41590-022-01272-5","article-title":"Lymph node homeostasis and adaptation to immune challenge resolved by fibroblast network mechanics","volume":"23","author":"Horsnell","year":"2022","journal-title":"Nat. Immunol."},{"key":"2025033106242904900_EBC-2025-3008C109","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.kint.2018.08.040","article-title":"Activation of fibroblastic reticular cells in kidney lymph node during crescentic glomerulonephritis","volume":"95","author":"Kasinath","year":"2019","journal-title":"Kidney Int."},{"key":"2025033106242904900_EBC-2025-3008C110","doi-asserted-by":"crossref","DOI":"10.1172\/JCI166070","article-title":"Tumor-activated lymph node fibroblasts suppress T cell function in diffuse large B cell lymphoma","volume":"133","author":"Apollonio","year":"2023","journal-title":"J. Clin. Invest."},{"key":"2025033106242904900_EBC-2025-3008C111","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1158\/0008-5472.CAN-21-0501","article-title":"Secretion of IL1 by dedifferentiated melanoma cells inhibits JAK1-STAT3-driven actomyosin contractility of lymph node fibroblastic reticular cells","volume":"82","author":"Rovera","year":"2022","journal-title":"Cancer Res."},{"key":"2025033106242904900_EBC-2025-3008C112","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.cell.2024.10.042","article-title":"Fibroblastic reticular cells generate protective intratumoral T cell environments in lung cancer","volume":"188","author":"Onder","year":"2025","journal-title":"Cell"},{"key":"2025033106242904900_EBC-2025-3008C113","article-title":"Predicting liposome formulations by the integrated machine learning and molecular modeling approaches","volume":"18","author":"Han","year":"2023","journal-title":"Asian J. Pharm. Sci."},{"key":"2025033106242904900_EBC-2025-3008C114","doi-asserted-by":"crossref","first-page":"10804","DOI":"10.1038\/s41467-024-55072-6","article-title":"Artificial intelligence-driven rational design of ionizable lipids for mRNA delivery","volume":"15","author":"Wang","year":"2024","journal-title":"Nat. Commun."}],"container-title":["Essays in Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/essaysbiochem\/article-pdf\/doi\/10.1042\/EBC20253008\/971254\/ebc-2025-3008.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/essaysbiochem\/article-pdf\/doi\/10.1042\/EBC20253008\/971254\/ebc-2025-3008.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T02:32:47Z","timestamp":1743388367000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/essaysbiochem\/article\/doi\/10.1042\/EBC20253008\/235905\/Emerging-strategies-in-lymph-node-targeted-nano"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,28]]},"references-count":114,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2025,3,28]]}},"URL":"https:\/\/doi.org\/10.1042\/ebc20253008","relation":{},"ISSN":["0071-1365","1744-1358"],"issn-type":[{"value":"0071-1365","type":"print"},{"value":"1744-1358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,28]]},"article-number":"EBC20253008"}}