{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:03:41Z","timestamp":1786982621680,"version":"build-2736575974"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017804","name":"City of Hope","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017804","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drug Deliv. and Transl. Res."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Intratumoral injection of immune stimulants could potentially reverse the immunosuppressive tumor microenvironment, but the injected drug rapidly washes out into the systemic circulation. This results in systemic toxicity, and reduced efficacy, potentially requiring daily injections to generate an antitumor immune response. To address this problem, we developed an extended-release hydrogel that retains the immunotherapy agent at the injection site, and releases it over several days, even in highly vascular liver tumors. The extended-release hydrogel is a composite material containing drug-loaded microspheres (for sustained, tunable drug release), embedded in a radiopaque cross-linked hydrogel (for local retention). Using these new intratumoral drug carriers, we demonstrate the ability to safely deliver a wide range of different immunotherapy agents (cytokines, oligonucleotides, small molecules) into pig liver tumors, with no acute systemic toxicity. The microsphere gel reduces burst release by 7.8x (compared to microspheres), and increases half-life by &gt;\u200915x (compared to hydrogel). Thus, the immunotherapy-loaded microsphere gel enables sustained intratumoral delivery of immune stimulants from a single injection, with low systemic toxicity.<\/jats:p>","DOI":"10.1007\/s13346-026-02176-9","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T06:10:07Z","timestamp":1782972607000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Radiopaque microsphere-hydrogel composite for extended-release intratumoral immunotherapy in a large animal model"],"prefix":"10.1007","author":[{"given":"Anup Kumar","family":"Patel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran Shair","family":"Mohammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Kortylewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven T","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Kessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Ressler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherng H","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taedo Jake","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandana","family":"Lall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Edward","family":"Boas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"2176_CR1","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1148\/radiol.2532082021","volume":"253","author":"M Kuang","year":"2009","unstructured":"Kuang M, Lu MD, Xie XY, Xu HX, Xu ZF, Liu GJ, et al., Lencioni R. Ethanol ablation of hepatocellular carcinoma Up to 5.0 cm by using a multipronged injection needle with high-dose strategy. Radiology. 2009;253:552\u201361.","journal-title":"Radiology"},{"key":"2176_CR2","doi-asserted-by":"publisher","first-page":"e0234535","DOI":"10.1371\/journal.pone.0234535","volume":"16","author":"C Nief","year":"2021","unstructured":"Nief C, Morhard R, Chelales E, Adrianzen Alvarez D, Bourla Bs I, et al. Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model. PLoS ONE. 2021;16:e0234535.","journal-title":"PLoS ONE"},{"key":"2176_CR3","doi-asserted-by":"crossref","unstructured":"Shyr CR, Liu LC, Chien HS, Huang CP. Immunotherapeutic agents for intratumoral immunotherapy, Vaccines (Basel), 11 (2023).","DOI":"10.3390\/vaccines11111717"},{"key":"2176_CR4","first-page":"A241","volume":"8","author":"R Murthy","year":"2020","unstructured":"Murthy R, Sheth R, Tam A, Gupta S, Subbiah V, Janku F, et al. 397\u2005Intra-tumor immunotherapy injections utilizing image guidance in interventional radiology: clinical trial experience at a tertiary care cancer center. J Immunother Cancer. 2020;8:A241\u20132.","journal-title":"J Immunother Cancer"},{"key":"2176_CR5","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/s41573-024-00974-9","volume":"23","author":"N Gong","year":"2024","unstructured":"Gong N, Alameh MG, El-Mayta R, Xue L, Weissman D, Mitchell MJ. Enhancing in situ cancer vaccines using delivery technologies. Nat Rev Drug Discov. 2024;23:607\u201325.","journal-title":"Nat Rev Drug Discov"},{"key":"2176_CR6","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/s41571-022-00719-w","volume":"20","author":"SZ Shalhout","year":"2023","unstructured":"Shalhout SZ, Miller DM, Emerick KS, Kaufman HL. Therapy with oncolytic viruses: progress and challenges. Nat Rev Clin Oncol. 2023;20:160\u201377.","journal-title":"Nat Rev Clin Oncol"},{"key":"2176_CR7","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s40164-024-00542-2","volume":"13","author":"X Gu","year":"2024","unstructured":"Gu X, Zhang Y, Zhou W, Wang F, Yan F, Gao H, et al. Infusion and delivery strategies to maximize the efficacy of CAR-T cell immunotherapy for cancers. Exp Hematol Oncol. 2024;13:70.","journal-title":"Exp Hematol Oncol"},{"key":"2176_CR8","doi-asserted-by":"publisher","first-page":"e007162","DOI":"10.1136\/jitc-2023-007162","volume":"11","author":"S Papa","year":"2023","unstructured":"Papa S, Adami A, Metoudi M, Beatson R, George MS, Achkova D, et al. Intratumoral pan-ErbB targeted CAR-T for head and neck squamous cell carcinoma: interim analysis of the T4 immunotherapy study. J Immunother Cancer. 2023;11:e007162.","journal-title":"J Immunother Cancer"},{"key":"2176_CR9","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1093\/neuonc\/noad087","volume":"25","author":"MC Burger","year":"2023","unstructured":"Burger MC, Forster MT, Romanski A, Strassheimer F, Macas J, Zeiner PS, et al. Intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma. Neuro Oncol. 2023;25:2058\u201371.","journal-title":"Neuro Oncol"},{"key":"2176_CR10","doi-asserted-by":"publisher","first-page":"100777","DOI":"10.1016\/j.tranon.2020.100777","volume":"13","author":"M Kitahara","year":"2020","unstructured":"Kitahara M, Mizukoshi E, Terashima T, Nakagawa H, Horii R, Iida N, et al. safety and long-term outcome of intratumoral injection of OK432-stimulated dendritic cells for hepatocellular carcinomas after radiofrequency ablation. Transl Oncol. 2020;13:100777.","journal-title":"Transl Oncol"},{"key":"2176_CR11","doi-asserted-by":"publisher","first-page":"e2301848","DOI":"10.1002\/adhm.202301848","volume":"13","author":"A Som","year":"2024","unstructured":"Som A, Rosenboom JG, Wehrenberg-Klee E, Chandler A, Ndakwah G, Chen E, et al., Percutaneous intratumoral immunoadjuvant gel increases the abscopal effect of cryoablation for checkpoint inhibitor resistant cancer. Adv Healthc Mater. 2024;13:e2301848.","journal-title":"Adv Healthc Mater"},{"key":"2176_CR12","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1016\/j.jvir.2023.03.016","volume":"34","author":"MA Ghani","year":"2023","unstructured":"Ghani MA, Bangar A, Yang Y, Jung E, Sauceda C, Mandt T, et al. Treatment of hepatocellular carcinoma by multimodal in situ vaccination using cryoablation and a plant virus immunostimulant. J Vasc Interv Radiol. 2023;34:1247\u2013e12571248.","journal-title":"J Vasc Interv Radiol"},{"key":"2176_CR13","doi-asserted-by":"publisher","first-page":"10236","DOI":"10.1021\/acsnano.3c00418","volume":"17","author":"Y Zhang","year":"2023","unstructured":"Zhang Y, Rahman MM, Clark PA, Sriramaneni RN, Havighurst T, Kerr CP, et al. In situ vaccination following intratumoral injection of IL2 and Poly-l-lysine\/Iron Oxide\/CpG nanoparticles to a radiated tumor site. ACS Nano. 2023;17:10236\u201351.","journal-title":"ACS Nano"},{"key":"2176_CR14","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1158\/0008-5472.CAN-21-1382","volume":"82","author":"WX Hong","year":"2022","unstructured":"Hong WX, Sagiv-Barfi I, Czerwinski DK, Sallets A, Levy R. Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer. Cancer Res. 2022;82:1396\u2013408.","journal-title":"Cancer Res"},{"key":"2176_CR15","doi-asserted-by":"publisher","first-page":"e002408","DOI":"10.1136\/jitc-2021-002408","volume":"9","author":"C Anfray","year":"2021","unstructured":"Anfray C, Mainini F, Digifico E, Maeda A, Sironi M, Erreni M, et al. Intratumoral combination therapy with poly(I:C) and resiquimod synergistically triggers tumor-associated macrophages for effective systemic antitumoral immunity. J Immunother Cancer. 2021;9:e002408.","journal-title":"J Immunother Cancer"},{"key":"2176_CR16","doi-asserted-by":"publisher","first-page":"4490","DOI":"10.1111\/cas.15145","volume":"112","author":"Y Chu","year":"2021","unstructured":"Chu Y, Li R, Qian L, Liu F, Xu R, Meng F, et al. Tumor eradicated by combination of imiquimod and OX40 agonist for in situ vaccination. Cancer Sci. 2021;112:4490\u2013500.","journal-title":"Cancer Sci"},{"issue":"2","key":"2176_CR17","doi-asserted-by":"publisher","first-page":"e002408","DOI":"10.1172\/JCI137001","volume":"131","author":"D Moreira","year":"2021","unstructured":"Moreira D, Sampath S, Won H, White SV, Su YL, Alcantara M, et al. Myeloid cell-targeted STAT3 inhibition sensitizes head and neck cancers to radiotherapy and T cell-mediated immunity. J Clin Invest. 2021;131(2):e002408.","journal-title":"J Clin Invest"},{"issue":"5","key":"2176_CR18","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1038\/s41591-019-0410-x","volume":"25","author":"L Hammerich","year":"2019","unstructured":"Hammerich L, Marron TU, Upadhyay R, Svensson-Arvelund J, Dhainaut M, Hussein S, et al. Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination. Nat Med. 2019;25(5):814\u201324.","journal-title":"Nat Med"},{"key":"2176_CR19","doi-asserted-by":"publisher","first-page":"eaaz6606","DOI":"10.1126\/scitranslmed.aaz6606","volume":"12","author":"X Lu","year":"2020","unstructured":"Lu X, Miao L, Gao W, Chen Z, McHugh KJ, Sun Y, et al. Engineered PLGA microparticles for long-term, pulsatile release of STING agonist for cancer immunotherapy. Sci Transl Med. 2020;12:eaaz6606.","journal-title":"Sci Transl Med"},{"key":"2176_CR20","doi-asserted-by":"publisher","first-page":"e232654","DOI":"10.1148\/radiol.232654","volume":"312","author":"R.A. Sheth","year":"2024","unstructured":"Sheth R.A., Wehrenberg-Klee E, Patel SP, Brock KK, Fotiadis N, de Baere T. Intratumoral Injection of Immunotherapeutics: State of the Art and Future Directions. Radiology. 2024;312:e232654.","journal-title":"Radiology"},{"key":"2176_CR21","doi-asserted-by":"publisher","first-page":"115083","DOI":"10.1016\/j.addr.2023.115083","volume":"202","author":"AS Mikhail","year":"2023","unstructured":"Mikhail AS, Morhard R, Mauda-Havakuk M, Kassin M, Arrichiello A, Wood BJ. Hydrogel drug delivery systems for minimally invasive local immunotherapy of cancer. Adv Drug Deliv Rev. 2023;202:115083.","journal-title":"Adv Drug Deliv Rev"},{"key":"2176_CR22","doi-asserted-by":"publisher","first-page":"e001800","DOI":"10.1136\/jitc-2020-001800","volume":"9","author":"NM Munoz","year":"2021","unstructured":"Munoz NM, Williams M, Dixon K, Dupuis C, McWatters A, Avritscher R, et al. Influence of injection technique, drug formulation and tumor microenvironment on intratumoral immunotherapy delivery and efficacy. J Immunother Cancer. 2021;9:e001800.","journal-title":"J Immunother Cancer"},{"key":"2176_CR23","doi-asserted-by":"publisher","first-page":"27782","DOI":"10.1038\/s41598-024-79694-4","volume":"14","author":"F Pedersoli","year":"2024","unstructured":"Pedersoli F, Mohammad IS, Patel AK, Kessler J, Chao C, Liu B, et al. Bioinspired intratumoral infusion port catheter improves local drug delivery in the liver. Sci Rep. 2024;14:27782.","journal-title":"Sci Rep"},{"key":"2176_CR24","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/s13566-017-0315-6","volume":"6","author":"RC Bakker","year":"2017","unstructured":"Bakker RC, Lam M, van Nimwegen SA, Rosenberg A, van Es RJJ, Nijsen JFW. Intratumoral treatment with radioactive beta-emitting microparticles: a systematic review. J Radiat Oncol. 2017;6:323\u201341.","journal-title":"J Radiat Oncol"},{"key":"2176_CR25","doi-asserted-by":"publisher","first-page":"eabb6594","DOI":"10.1126\/sciadv.abb6594","volume":"6","author":"M Sarmadi","year":"2020","unstructured":"Sarmadi M, Behrens AM, McHugh KJ, Contreras HTM, Tochka ZL, Lu X, et al. Modeling, design, and machine learning-based framework for optimal injectability of microparticle-based drug formulations. Sci Adv. 2020;6:eabb6594.","journal-title":"Sci Adv"},{"key":"2176_CR26","doi-asserted-by":"publisher","first-page":"6053","DOI":"10.1021\/acsbiomaterials.0c01228","volume":"6","author":"J Yoo","year":"2020","unstructured":"Yoo J, Won YY. Phenomenology of the initial burst release of drugs from PLGA microparticles. ACS Biomater Sci Eng. 2020;6:6053\u201362.","journal-title":"ACS Biomater Sci Eng"},{"key":"2176_CR27","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1148\/radiol.2021210213","volume":"301","author":"FE Boas","year":"2021","unstructured":"Boas FE, Kemeny NE, Sofocleous CT, Yeh R, Thompson VR, Hsu M, et al. Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical Trial. Radiology. 2021;301:474\u201384.","journal-title":"Radiology"},{"key":"2176_CR28","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/j.jvir.2020.09.011","volume":"32","author":"F Nurili","year":"2021","unstructured":"Nurili F, Monette S, Michel AO, Bendet A, Basturk O, Askan G, et al. Transarterial embolization of liver cancer in a transgenic Pig model. J Vasc Interv Radiol. 2021;32:510\u2013e517513.","journal-title":"J Vasc Interv Radiol"},{"key":"2176_CR29","unstructured":"Boas FE, Basturk O, Yin Z, Yarmohammadi H, Elkhadragy L, Chiang J, et al. Undifferentiated carcinomas in a large animal model of liver cancer. Anim Model Exp Med, (2026)."},{"key":"2176_CR30","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1126\/science.276.5309.122","volume":"276","author":"GB West","year":"1997","unstructured":"West GB, Brown JH, Enquist BJ. A general model for the origin of allometric scaling laws in biology. Science. 1997;276:122\u20136.","journal-title":"Science"},{"key":"2176_CR31","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9781139167826","volume-title":"Scaling: Why is animal size so important?","author":"K Schmidt-Nielsen","year":"1984","unstructured":"Schmidt-Nielsen K. Scaling: Why is animal size so important? New York: Cambridge University Press; 1984."},{"key":"2176_CR32","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4103\/0976-0105.177703","volume":"7","author":"AB Nair","year":"2016","unstructured":"Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7:27\u201331.","journal-title":"J Basic Clin Pharm"},{"key":"2176_CR33","first-page":"114","volume":"6","author":"IW Mak","year":"2014","unstructured":"Mak IW, Evaniew N, Ghert M. Lost in translation: animal models and clinical trials in cancer treatment. Am J Transl Res. 2014;6:114\u20138.","journal-title":"Am J Transl Res"},{"key":"2176_CR34","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/s41591-020-1131-x","volume":"27","author":"J Yu","year":"2021","unstructured":"Yu J, Green MD, Li S, Sun Y, Journey SN, Choi JE, et al. Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination. Nat Med. 2021;27:152\u201364.","journal-title":"Nat Med"},{"key":"2176_CR35","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1126\/science.adl4100","volume":"387","author":"SK Varanasi","year":"2025","unstructured":"Varanasi SK, Chen D, Liu Y, Johnson MA, Miller CM, Ganguly S, et al. Bile acid synthesis impedes tumor-specific T cell responses during liver cancer. Science. 2025;387:192\u2013201.","journal-title":"Science"},{"key":"2176_CR36","doi-asserted-by":"publisher","first-page":"2705","DOI":"10.1016\/j.ymthe.2025.02.045","volume":"33","author":"V DeFranciscis","year":"2025","unstructured":"DeFranciscis V, Amabile G, Kortylewski M. Clinical applications of oligonucleotides for cancer therapy. Mol Ther. 2025;33:2705\u201318.","journal-title":"Mol Ther"},{"key":"2176_CR37","doi-asserted-by":"publisher","first-page":"114857","DOI":"10.1016\/j.addr.2023.114857","volume":"198","author":"B Wan","year":"2023","unstructured":"Wan B, Bao Q, Burgess D. Long-acting PLGA microspheres: Advances in excipient and product analysis toward improved product understanding. Adv Drug Deliv Rev. 2023;198:114857.","journal-title":"Adv Drug Deliv Rev"},{"key":"2176_CR38","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.jconrel.2023.04.028","volume":"357","author":"J Kim","year":"2023","unstructured":"Kim J, Archer PA, Manspeaker MP, Avecilla ARC, Pollack BP, Thomas SN. Sustained release hydrogel for durable locoregional chemoimmunotherapy for BRAF-mutated melanoma. J Control Release. 2023;357:655\u201368.","journal-title":"J Control Release"},{"key":"2176_CR39","doi-asserted-by":"publisher","first-page":"e0310345","DOI":"10.1371\/journal.pone.0310345","volume":"19","author":"JF Delgado","year":"2024","unstructured":"Delgado JF, Negussie AH, Varble NA, Mikhail AS, Arrichiello A, Borde T, et al. In vivo imaging and pharmacokinetics of percutaneously injected ultrasound and X-ray imageable thermosensitive hydrogel loaded with doxorubicin versus free drug in swine. PLoS ONE. 2024;19:e0310345.","journal-title":"PLoS ONE"},{"key":"2176_CR40","doi-asserted-by":"publisher","first-page":"2748","DOI":"10.1016\/j.biomaterials.2013.01.006","volume":"34","author":"HW Seo","year":"2013","unstructured":"Seo HW, Kim DY, Kwon DY, Kwon JS, Jin LM, Lee B, et al. Injectable intratumoral hydrogel as 5-fluorouracil drug depot. Biomaterials. 2013;34:2748\u201357.","journal-title":"Biomaterials"},{"key":"2176_CR41","doi-asserted-by":"publisher","first-page":"3781","DOI":"10.1038\/s41467-025-59278-0","volume":"16","author":"R Bhatta","year":"2025","unstructured":"Bhatta R, Han J, Liu Y, Bo Y, Wang Y, Nguyen D, et al. Injectable extracellular vesicle hydrogels with tunable viscoelasticity for depot vaccine. Nat Commun. 2025;16:3781.","journal-title":"Nat Commun"},{"key":"2176_CR42","doi-asserted-by":"publisher","first-page":"e2406080","DOI":"10.1002\/adma.202406080","volume":"36","author":"H Albadawi","year":"2024","unstructured":"Albadawi H, Zhang Z, Keum H, Cevik E, Nagalo BM, Gunduz S, et al. Percutaneous delivery of oncogel for targeted liver tumor ablation and controlled release of therapeutics. Adv Mater. 2024;36:e2406080.","journal-title":"Adv Mater"},{"key":"2176_CR43","doi-asserted-by":"publisher","first-page":"18604","DOI":"10.1021\/acsnano.4c04766","volume":"18","author":"X Yang","year":"2024","unstructured":"Yang X, Huang C, Wang H, Yang K, Huang M, Zhang W, et al. Multifunctional nanoparticle-loaded injectable alginate hydrogels with deep tumor penetration for enhanced chemo-immunotherapy of cancer. ACS Nano. 2024;18:18604\u201321.","journal-title":"ACS Nano"},{"key":"2176_CR44","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1021\/acs.biomac.3c00591","volume":"25","author":"P Gierlich","year":"2024","unstructured":"Gierlich P, Donohoe C, Behan K, Kelly D.J., Senge M.O., Gomes-da-Silva L.C. Antitumor Immunity Mediated by Photodynamic Therapy Using Injectable Chitosan Hydrogels for Intratumoral and Sustained Drug Delivery. Biomacromolecules. 2024;25:24\u201342.","journal-title":"Biomacromolecules"},{"key":"2176_CR45","doi-asserted-by":"publisher","first-page":"5339","DOI":"10.1021\/acs.biomac.1c01279","volume":"22","author":"E Mei","year":"2021","unstructured":"Mei E, Chen C, Li C, Ding X, Chen J, Xi Q, et al. Injectable and Biodegradable Chitosan Hydrogel-Based Drug Depot Contributes to Synergistic Treatment of Tumors. Biomacromolecules. 2021;22:5339\u201348.","journal-title":"Biomacromolecules"},{"key":"2176_CR46","doi-asserted-by":"publisher","first-page":"628895","DOI":"10.3389\/fonc.2021.628895","volume":"11","author":"Q Gao","year":"2021","unstructured":"Gao Q, Jiang Y, Li X, Chen H, Tang S, Chen H, et al. Intratumoral injection of anlotinib hydrogel combined with radiotherapy reduces hypoxia in lewis lung carcinoma xenografts: assessment by micro fluorine-18-fluoromisonidazole positron emission tomography\/computed tomography hypoxia imaging. Front Oncol. 2021;11:628895.","journal-title":"Front Oncol"},{"key":"2176_CR47","doi-asserted-by":"publisher","first-page":"122006","DOI":"10.1016\/j.biomaterials.2023.122006","volume":"294","author":"G Catania","year":"2023","unstructured":"Catania G, Rodella G, Vanvarenberg K, Preat V, Malfanti A. Combination of hyaluronic acid conjugates with immunogenic cell death inducer and CpG for glioblastoma local chemo-immunotherapy elicits an immune response and induces long-term survival. Biomaterials. 2023;294:122006.","journal-title":"Biomaterials"},{"key":"2176_CR48","doi-asserted-by":"publisher","first-page":"2400246","DOI":"10.1002\/adtp.202400246","volume":"7","author":"HJ Ju","year":"2024","unstructured":"Ju HJ, Kim MJ, Kim S, Son KE, Lee MY, Kim HS, et al. Enhanced anticancer effects of intratumorally injected electrostatic doxorubicin-loaded click-type crosslinked hyaluronic acid hydrogel. Adv Ther-Germany. 2024;7:2400246.","journal-title":"Adv Ther-Germany"}],"container-title":["Drug Delivery and Translational Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-026-02176-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13346-026-02176-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-026-02176-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:05:53Z","timestamp":1782975953000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13346-026-02176-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":48,"alternative-id":["2176"],"URL":"https:\/\/doi.org\/10.1007\/s13346-026-02176-9","relation":{},"ISSN":["2190-393X","2190-3948"],"issn-type":[{"value":"2190-393X","type":"print"},{"value":"2190-3948","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"assertion":[{"value":"20 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 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":"Clinical trial number: not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards"}},{"value":"MK is a co-founder of Twin Peaks, Forta and AptaDiR Therapeutics with stock options. He is a co-inventor of CpG-STAT3ASO strategy with pending patent application. STR is founder and chair of the scientific advisory board at SLAM bio and Noval Biotech. He is on the scientific advisory board of Cizzle. He is on the board of directors of Zylem. JK received a grant from Metavivor, and consulting fees from Johnson and Johnson, Boston Scientific, and Galvanize Therapeutics. CHC received support for attending meetings from Boston Scientific and Stryker. He is a co-investigator on studies funded by Instylla and CrannMed. FEB received research grants from City of Hope, Guerbet, Stephenson fund, COH-Caltech Biomedical Research Initiative (Merkin Institute), Society of Interventional Radiology, Society of Interventional Oncology, NIH\/NCI, Department of Defense, Thompson family foundation, and Brockman Medical Research Foundation. He received research supplies (investigator-initiated) from Boston Scientific, and attended research consensus panels with the Society of Interventional Oncology. He is a co-founder of Claripacs, LLC, and an investor in Labdoor, Qventus, CloudMedx, Xgenomes, and Solugen. He has patent applications covering intratumoral drug delivery devices, immunoembolization, Y90 dosimetry, endoluminal ablation, CT metal artifact reduction, and other inventions.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}}]}}