{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:59:03Z","timestamp":1792724343551,"version":"4.5.0"},"reference-count":27,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFE0108100"],"award-info":[{"award-number":["2024YFE0108100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["20DZ2254900"],"award-info":[{"award-number":["20DZ2254900"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["23520712500"],"award-info":[{"award-number":["23520712500"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["24490711000"],"award-info":[{"award-number":["24490711000"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["CUSF-DH-T-2025011"],"award-info":[{"award-number":["CUSF-DH-T-2025011"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52350710203"],"award-info":[{"award-number":["52350710203"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A2096"],"award-info":[{"award-number":["U23A2096"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["W2421104"],"award-info":[{"award-number":["W2421104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Development of efficient and stimuli-responsive gene delivery systems for therapeutic protein expression and immunomodulation remains challenging. Here, we report the synthesis of three types of pH-, reactive oxygen species (ROS)- and glutathione (GSH)-responsive dendrimer nanogels (for short, DNGs-pH, DNGs-ROS, and DNGs-GSH, respectively) via a microemulsion method for delivery of messenger RNA (mRNA) and plasmid DNA (pDNA), both encoding enhanced green fluorescent protein (for short, mEGFP and pEGFP), to dendritic cells (DCs). The synthesized DNGs exhibit a nanoscale dimension, high monodispersity, desired colloidal stability, low cytotoxicity, and efficient gene delivery efficiency. Importantly, the DNG-pH\/mEGFP polyplexes exhibit a superior transfection performance to DCs, achieving 3.6-fold and 1.2-fold higher EGFP expression than the DNG-GSH\/mEGFP and DNG-ROS\/mEGFP, likely attributable to the synergistic proton sponge-mediated endosomal escape and pH-responsive dissociation of the DNGs. The developed pH-responsive DNGs could be an important candidate for highly efficient gene delivery to DCs for immune modulation.<\/jats:p>","DOI":"10.1021\/acs.biomac.5c01272","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T04:44:07Z","timestamp":1757047447000},"page":"6962-6972","source":"Crossref","is-referenced-by-count":9,"title":["Impact of Stimuli-Responsiveness\non the mRNA Delivery\nEfficiency of Low-Generation Dendrimer Nanogels"],"prefix":"10.1021","volume":"26","author":[{"given":"Xianghao","family":"Xiao","sequence":"first","affiliation":[{"name":"Donghua University , , ,","place":["Shanghai, China, 201620"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3613-1980","authenticated-orcid":true,"given":"Yue","family":"Gao","sequence":"additional","affiliation":[{"name":"Donghua University , , ,","place":["Shanghai, China, 201620"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Jia","sequence":"additional","affiliation":[{"name":"Donghua University , , ,","place":["Shanghai, China, 201620"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1065-0854","authenticated-orcid":true,"given":"Mingwu","family":"Shen","sequence":"additional","affiliation":[{"name":"Donghua University , , ,","place":["Shanghai, China, 201620"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1825-7798","authenticated-orcid":true,"given":"Andrij","family":"Pich","sequence":"additional","affiliation":[{"name":"DWI-Leibniz-Institute for Interactive Materials , ,","place":["Aachen, Germany, 52074"]},{"name":"RWTH Aachen University , , ,","place":["Aachen, Germany, 52074"]},{"name":"Maastricht University , , ,","place":["Geleen, The Netherlands, 6167 RD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6785-6645","authenticated-orcid":true,"given":"Xiangyang","family":"Shi","sequence":"additional","affiliation":[{"name":"Donghua University , , ,","place":["Shanghai, China, 201620"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"issue":"8","key":"2026081812201316400_cit1","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1056\/nejmoa2211644","article-title":"Gene Therapy with Etranacogene Dezaparvovec\nfor Hemophilia B","volume":"388","author":"Pipe","year":"2023","journal-title":"N. Engl. J. Med."},{"issue":"1","key":"2026081812201316400_cit2","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/s41392-022-01007-w","article-title":"mRNA-Based Therapeutics:\nPowerful and Versatile Tools\nto Combat Diseases","volume":"7","author":"Qin","year":"2022","journal-title":"Signal Transduction Targeted\nTher."},{"issue":"8","key":"2026081812201316400_cit3","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1038\/s41568-023-00586-2","article-title":"mRNA-Based\nCancer Therapeutics","volume":"23","author":"Liu","year":"2023","journal-title":"Nat. Rev. Cancer"},{"issue":"11","key":"2026081812201316400_cit4","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1038\/s41587-022-01491-z","article-title":"Unlocking\nthe Promise of mRNA Therapeutics","volume":"40","author":"Rohner","year":"2022","journal-title":"Nat. Biotechnol."},{"issue":"51","key":"2026081812201316400_cit5","doi-asserted-by":"publisher","first-page":"2303261","DOI":"10.1002\/adma.202303261","article-title":"Lipid Nanoparticle (LNP) Enables\nmRNA Delivery for Cancer Therapy","volume":"35","author":"Zong","year":"2023","journal-title":"Adv. Mater."},{"issue":"6","key":"2026081812201316400_cit6","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1016\/j.matt.2022.03.006","article-title":"The Roles\nof Polymers\nin mRNA Delivery","volume":"5","author":"Huang","year":"2022","journal-title":"Matter"},{"issue":"12","key":"2026081812201316400_cit7","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","article-title":"Lipid Nanoparticles\nfor mRNA Delivery","volume":"6","author":"Hou","year":"2021","journal-title":"Nat. Rev. Mater."},{"issue":"11","key":"2026081812201316400_cit8","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/s41571-023-00811-9","article-title":"Targeting Cancer with mRNA\u2013Lipid\nNanoparticles: Key Considerations\nand Future Prospects","volume":"20","author":"Kon","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"2026081812201316400_cit9","doi-asserted-by":"publisher","first-page":"102437","DOI":"10.1016\/j.nantod.2024.102437","article-title":"Core-Shell\nTecto Dendrimers Co-Deliver Drug\/Gene for Immunomodulation of Macrophages\nand Dendritic Cells and Checkpoint Blockade-Promoted Breast Cancer\nChemoimmunotherapy","volume":"58","author":"Song","year":"2024","journal-title":"Nano Today"},{"key":"2026081812201316400_cit10","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1016\/j.jconrel.2023.03.011","article-title":"Precise and Systematic\nEnd Group\nChemistry Modifications on PAMAM and Poly\u00ad(l-Lysine) Dendrimers to\nImprove Cytosolic Delivery of mRNA","volume":"356","author":"Joubert","year":"2023","journal-title":"J. Controlled\nRelease"},{"issue":"23","key":"2026081812201316400_cit11","doi-asserted-by":"publisher","first-page":"23889","DOI":"10.1021\/acsnano.3c08174","article-title":"Manganese\nDioxide-Entrapping\nDendrimers Co-Deliver Protein and Nucleotide for Magnetic Resonance\nImaging-Guided Chemodynamic\/Starvation\/Immune Therapy of Tumors","volume":"17","author":"Gao","year":"2023","journal-title":"ACS Nano"},{"issue":"9","key":"2026081812201316400_cit12","doi-asserted-by":"publisher","first-page":"7168","DOI":"10.1021\/acsabm.1c00743","article-title":"Facile Formation of PAMAM Dendrimer Nanoclusters for Enhanced Gene\nDelivery and Cancer Gene Therapy","volume":"4","author":"Mekuria","year":"2021","journal-title":"ACS Appl.\nBio Mater."},{"issue":"38","key":"2026081812201316400_cit13","doi-asserted-by":"publisher","first-page":"9524","DOI":"10.1039\/D4TB01747A","article-title":"Dendrimer Nanoclusters Loaded with Gold Nanoparticles\nfor Enhanced Tumor CT Imaging and Chemotherapy via an Amplified EPR\nEffect","volume":"12","author":"Mekuria","year":"2024","journal-title":"J. Mater. Chem. B"},{"issue":"31","key":"2026081812201316400_cit14","doi-asserted-by":"publisher","first-page":"6149","DOI":"10.1039\/D1TB01328A","article-title":"Impact of\nMolecular Rigidity on the Gene Delivery Efficiency of Core-Shell Tecto\nDendrimers","volume":"9","author":"Wang","year":"2021","journal-title":"J. Mater. Chem. B"},{"issue":"22","key":"2026081812201316400_cit15","doi-asserted-by":"publisher","first-page":"7387","DOI":"10.1039\/D3BM01198D","article-title":"Phosphorus\nCore-Shell Tecto Dendrimers for Enhanced\nTumor Imaging: the Rigidity of the Backbone Matters","volume":"11","author":"Zhan","year":"2023","journal-title":"Biomater. Sci."},{"issue":"2","key":"2026081812201316400_cit16","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1021\/acs.biomac.2c01403","article-title":"Multifunctional Low-Generation Dendrimer Nanogels as an Emerging\nProbe for Tumor-Specific CT\/MR Dual-Modal Imaging","volume":"24","author":"Xu","year":"2023","journal-title":"Biomacromolecules"},{"key":"2026081812201316400_cit17","doi-asserted-by":"publisher","DOI":"10.1007\/s11426-025-2737-5","article-title":"Exosome-Coated Responsive Dendrimer\nNanogels Enable\nCombined Immunomodulation and Antioxidant Treatment of Acute Lung\nInjury","volume":"68","author":"Li","year":"2025","journal-title":"Sci. China: Chem."},{"issue":"5","key":"2026081812201316400_cit18","doi-asserted-by":"publisher","first-page":"4946","DOI":"10.1021\/acs.chemrev.1c00330","article-title":"Hydrogen-Bonded Supramolecular Liquid\nCrystal Polymers:\nSmart Materials with Stimuli-Responsive, Self-Healing, and Recyclable\nProperties","volume":"122","author":"Lugger","year":"2022","journal-title":"Chem. Rev."},{"issue":"47","key":"2026081812201316400_cit19","doi-asserted-by":"publisher","first-page":"2206861","DOI":"10.1002\/adma.202206861","article-title":"Chemotherapy Mediated\nby Biomimetic Polymeric Nanoparticles Potentiates Enhanced Tumor Immunotherapy\nvia Amplification of Endoplasmic Reticulum Stress and Mitochondrial\nDysfunction","volume":"34","author":"Guo","year":"2022","journal-title":"Adv. Mater."},{"issue":"3","key":"2026081812201316400_cit20","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1021\/acs.biomac.1c01571","article-title":"Genetic Engineering\nof Dendritic Cells Using Partially Zwitterionic Dendrimer-Entrapped\nGold Nanoparticles Boosts Efficient Tumor Immunotherapy","volume":"23","author":"Ouyang","year":"2022","journal-title":"Biomacromolecules"},{"issue":"5","key":"2026081812201316400_cit21","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1002\/adhm.201500679","article-title":"Clustering Small Dendrimers\ninto Nanoaggregates for Efficient DNA and siRNA Delivery with Minimal\nToxicity","volume":"5","author":"Liu","year":"2016","journal-title":"Adv. Healthcare Mater."},{"issue":"22","key":"2026081812201316400_cit22","doi-asserted-by":"publisher","first-page":"9761","DOI":"10.1021\/acs.nanolett.1c03708","article-title":"A Duplex CRISPR-Cas9\nRibonucleoprotein\nNanomedicine for Colorectal Cancer Gene Therapy","volume":"21","author":"Wan","year":"2021","journal-title":"Nano Lett."},{"issue":"3","key":"2026081812201316400_cit23","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1021\/acs.bioconjchem.5b00666","article-title":"Temperature-Responsive Gene Silencing by a Smart Polymer","volume":"27","author":"Wang","year":"2016","journal-title":"Bioconjugate Chem."},{"key":"2026081812201316400_cit24","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.jconrel.2023.01.076","article-title":"Photothermal-Triggered\nDendrimer Nanovaccines Boost Systemic Antitumor Immunity","volume":"355","author":"Shen","year":"2023","journal-title":"J. Controlled Release"},{"issue":"1","key":"2026081812201316400_cit25","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1021\/bm701084w","article-title":"pH-Triggered\nReversible \u201cStealth\u201d Polycationic\nMicelles","volume":"9","author":"Gu","year":"2008","journal-title":"Biomacromolecules"},{"issue":"19","key":"2026081812201316400_cit26","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202300031","article-title":"Controlled\nDeformation of Soft Nanogel Particles Generates Artificial Biominerals\nwith Ordered Internal Structure","volume":"62","author":"Dong","year":"2023","journal-title":"Angew. Chem.,\nInt. Ed."},{"issue":"6","key":"2026081812201316400_cit27","doi-asserted-by":"publisher","first-page":"2502","DOI":"10.1021\/acs.biomac.0c00458","article-title":"Revisiting\nCationic Phosphorus Dendrimers as a Nonviral Vector for Optimized\nGene Delivery Toward Cancer Therapy Applications","volume":"21","author":"Chen","year":"2020","journal-title":"Biomacromolecules"}],"container-title":["Biomacromolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.biomac.5c01272","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/bomaf6\/article-pdf\/26\/10\/6962\/41119878\/bm5c01272.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/bomaf6\/article-pdf\/26\/10\/6962\/41119878\/bm5c01272.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:04:37Z","timestamp":1787076277000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/bomaf6\/article\/26\/10\/6962\/3682288\/Impact-of-Stimuli-Responsiveness-on-the-mRNA"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,5]]},"references-count":27,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,9,5]]},"published-print":{"date-parts":[[2025,10,13]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.biomac.5c01272","relation":{},"ISSN":["1525-7797","1526-4602"],"issn-type":[{"value":"1525-7797","type":"print"},{"value":"1526-4602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,5]]}}}