{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T22:02:54Z","timestamp":1784412174885,"version":"3.55.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["14974"],"award-info":[{"award-number":["14974"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["15066"],"award-info":[{"award-number":["15066"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drug Deliv. and Transl. Res."],"DOI":"10.1007\/s13346-026-02187-6","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T21:06:14Z","timestamp":1784408774000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The closer, the better: intratumoral delivery of a thermoresponsive gemcitabine-loaded hydrogel in preclinical PDAC models"],"prefix":"10.1007","author":[{"given":"Andrea","family":"Vall\u00e9s-Mart\u00ed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajinkya","family":"Manelkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Kinderman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveline","family":"de Jonge-Muller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthea","family":"van der Wielen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanus G.T.","family":"Janson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Alrawahneh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zihao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar","family":"Tomar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike G.W.","family":"de Leeuw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena M.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas J.A.C.","family":"Hawinkels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"issue":"11","key":"2187_CR1","doi-asserted-by":"publisher","first-page":"2913","DOI":"10.1158\/0008-5472.CAN-14-0155","volume":"74","author":"L Rahib","year":"2014","unstructured":"Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States. Cancer Res. 2014;74(11):2913\u201321.","journal-title":"Cancer Res"},{"issue":"11","key":"2187_CR2","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.annonc.2023.08.009","volume":"34","author":"T Conroy","year":"2023","unstructured":"Conroy T, Pfeiffer P, Vilgrain V, Lamarca A, Seufferlein T, O\u2019Reilly EM, et al. Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up\u2606. Ann Oncol. 2023;34(11):987\u20131002.","journal-title":"Ann Oncol"},{"key":"2187_CR3","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1016\/S0140-6736(25)00261-2","volume":"405","author":"TF Stoop","year":"2025","unstructured":"Stoop TF. Pancreatic cancer. Lancet. 2025;405:1182\u2013202.","journal-title":"Lancet"},{"issue":"25","key":"2187_CR4","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1056\/NEJMoa1809775","volume":"379","author":"T Conroy","year":"2018","unstructured":"Conroy T, Hammel P, Hebbar M, Abdelghani MB, Wei AC, Raoul J-L, et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018;379(25):2395\u2013406.","journal-title":"N Engl J Med"},{"issue":"6","key":"2187_CR5","doi-asserted-by":"publisher","first-page":"e2216199","DOI":"10.1001\/jamanetworkopen.2022.16199","volume":"5","author":"A Klein-Brill","year":"2022","unstructured":"Klein-Brill A, Amar-Farkash S, Lawrence G, Collisson EA, Aran D. FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel for Metastatic Pancreatic Cancer. JAMA Netw Open. 2022;5(6):e2216199.","journal-title":"JAMA Netw Open"},{"issue":"31","key":"2187_CR6","first-page":"e1298","volume":"94","author":"Y-G Chen","year":"2015","unstructured":"Chen Y-G, Pan H-H, Dai M-S, Lin C, Lu C-S, Su S-L, et al. Impact of Comorbidity and Age on Determinants Therapeutic Strategies in Advanced Pancreatic Head Cancer Patients With Obstructive Jaundices. Med August. 2015;94(31):e1298.","journal-title":"Med August"},{"key":"2187_CR7","first-page":"A532","volume":"153","author":"MAAJ van den Bosch","year":"2009","unstructured":"van den Bosch MAAJ, Prevoo W, van der Linden EM, Meijerink MR, van Delden OM, Mali WPTM, et al. [The radiologist as the treating physician for cancer: interventional oncology]. Ned Tijdschr Geneeskd. 2009;153:A532.","journal-title":"Ned Tijdschr Geneeskd"},{"issue":"4","key":"2187_CR8","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/j.drudis.2016.02.014","volume":"21","author":"F Ramazani","year":"2016","unstructured":"Ramazani F, Nostrum CFv, Storm G, Kiessling F, Lammers T, Hennink WE, et al. Locoregional cancer therapy using polymer-based drug depots. Drug Discovery Today. 2016;21(4):640\u20137.","journal-title":"Drug Discovery Today"},{"issue":"3","key":"2187_CR9","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1148\/radiol.10081490","volume":"257","author":"SB Solomon","year":"2010","unstructured":"Solomon SB, Silverman SG. Imaging in Interventional Oncology1. Radiology. 2010;257(3):624\u201340.","journal-title":"Radiology"},{"key":"2187_CR10","doi-asserted-by":"publisher","first-page":"216979","DOI":"10.1016\/j.canlet.2024.216979","volume":"594","author":"W Luo","year":"2024","unstructured":"Luo W, Zhang T. The new era of pancreatic cancer treatment: Application of nanotechnology breaking through bottlenecks. Cancer Lett. 2024;594:216979.","journal-title":"Cancer Lett"},{"issue":"2","key":"2187_CR11","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1211\/0022357021778268","volume":"54","author":"G EP","year":"2002","unstructured":"EP G, AR H, BA A. JS M. Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery - PubMed. J Pharm Pharmacol. 2002;54(2):159\u201380.","journal-title":"J Pharm Pharmacol"},{"issue":"3","key":"2187_CR12","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/s41416-020-0904-9","volume":"123","author":"SM Rossi","year":"2020","unstructured":"Rossi SM, Ryan BK, Kelly HM, Rossi SM, Ryan BK, Kelly HM. Evaluation of the activity of a chemo-ablative, thermoresponsive hydrogel in a murine xenograft model of lung cancer. Br J Cancer. 2020;123(3):369\u201377.","journal-title":"Br J Cancer"},{"issue":"10","key":"2187_CR13","doi-asserted-by":"publisher","first-page":"2028","DOI":"10.3390\/pharmaceutics14102028","volume":"14","author":"J Zhao","year":"2022","unstructured":"Zhao J, Wang L, Zhang H, Liao B, Li Y, Zhao J, et al. Progress of Research in In Situ Smart Hydrogels for Local Antitumor Therapy: A Review. Pharmaceutics. 2022;14(10):2028.","journal-title":"Pharmaceutics"},{"key":"2187_CR14","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.biomaterials.2016.02.001","volume":"85","author":"DY Kim","year":"2016","unstructured":"Kim DY, Kwon DY, Kwon JS, Park JH, Park SH, Oh HJ, et al. Synergistic anti-tumor activity through combinational intratumoral injection of an in-situ injectable drug depot. Biomaterials. 2016;85:232\u201345.","journal-title":"Biomaterials"},{"issue":"8","key":"2187_CR15","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.2217\/nnm.14.211","volume":"10","author":"H-J Jhan","year":"2015","unstructured":"Jhan H-J, Liu J-J, Chen Y-C, Liu D-Z, Sheu M-T, Ho H-O. Novel Injectable Thermosensitive Hydrogels for Delivering Hyaluronic Acid\u2013Doxorubicin Nanocomplexes to Locally Treat Tumors. Nanomedicine. 2015;10(8):1263\u201374.","journal-title":"Nanomedicine"},{"key":"2187_CR16","doi-asserted-by":"crossref","unstructured":"Sheu M-T, Jhan H-J, Su C-Y, Chen L-C, Chang C-E, Liu D-Z et al. Codelivery of doxorubicin-containing thermosensitive hydrogels incorporated with docetaxel-loaded mixed micelles enhances local cancer therapy. Colloids and Surfaces B: Biointerfaces. 2016;143.","DOI":"10.1016\/j.colsurfb.2016.03.054"},{"key":"2187_CR17","doi-asserted-by":"crossref","unstructured":"Li T, Zhang M, Wang J, Wang T, Yao Y, Zhang X, et al. Thermosensitive Hydrogel Co-loaded with Gold Nanoparticles and Doxorubicin for Effective Chemoradiotherapy. AAPS J. 2015;18(1).","DOI":"10.1208\/s12248-015-9828-3"},{"issue":"2","key":"2187_CR18","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s00270-018-2103-0","volume":"42","author":"SM Rossi","year":"2018","unstructured":"Rossi SM, Murray TE, Cassidy J, Lee MJ, Kelly HM, Rossi SM, et al. A Custom Radiopaque Thermoresponsive Chemotherapy-Loaded Hydrogel for Intratumoural Injection: An In Vitro and Ex Vivo Assessment of Imaging Characteristics and Material Properties. Cardiovasc Interventional Radiol. 2018;42(2):289\u201397.","journal-title":"Cardiovasc Interventional Radiol"},{"key":"2187_CR19","doi-asserted-by":"publisher","first-page":"v7","DOI":"10.1093\/annonc\/mdj941","volume":"17","author":"E Mini","year":"2006","unstructured":"Mini E, Nobili S, Caciagli B, Landini I, Mazzei T. Cellular pharmacology of gemcitabine. Ann Oncol. 2006;17:v7\u201312.","journal-title":"Ann Oncol"},{"key":"2187_CR20","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/B978-0-444-59499-0.00045-3","volume":"34","author":"F Murphy","year":"2012","unstructured":"Murphy F, Middleton M. Cytostatic and cytotoxic drugs. Side Eff Drugs Annual. 2012;34:731\u201347.","journal-title":"Side Eff Drugs Annual"},{"issue":"9","key":"2187_CR21","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1007\/s00262-004-0638-1","volume":"54","author":"JM Plate","year":"2005","unstructured":"Plate JM, Plate AE, Shott S, Bograd S, Harris JE. Effect of gemcitabine on immune cells in subjects with adenocarcinoma of the pancreas. Cancer Immunol Immunother. 2005;54(9):915\u201325.","journal-title":"Cancer Immunol Immunother"},{"issue":"12","key":"2187_CR22","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1093\/jjco\/hyp112","volume":"39","author":"A Soeda","year":"2009","unstructured":"Soeda A, Morita-Hoshi Y, Makiyama H, Morizane C, Ueno H, Ikeda M, et al. Regular Dose of Gemcitabine Induces an Increase in CD14\u2009+\u2009Monocytes and CD11c+ Dendritic Cells in Patients with Advanced Pancreatic Cancer. Jpn J Clin Oncol. 2009;39(12):797\u2013806.","journal-title":"Jpn J Clin Oncol"},{"key":"2187_CR23","doi-asserted-by":"crossref","unstructured":"Butenko S, Nagalla RR, Guerrero-Juarez CF, Palomba F, David L-M, Nguyen RQ, et al. Hydrogel crosslinking modulates macrophages, fibroblasts, and their communication, during wound healing. Nat Commun. 2024;15(1).","DOI":"10.1038\/s41467-024-50072-y"},{"key":"2187_CR24","first-page":"7217","volume":"106","author":"G Lencioni","year":"2024","unstructured":"Lencioni G, Gregori A, Toledo B, Rebelo R, Immordino B, Amrutkar M, et al. Unravelling the complexities of resistance mechanism in pancreatic cancer: Insights from in vitro and ex-vivo model systems. Sem Cancer Biol. 2024;106:7217\u2013233.","journal-title":"Sem Cancer Biol"},{"key":"2187_CR25","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.jconrel.2015.11.014","volume":"220","author":"A Fakhari","year":"2015","unstructured":"Fakhari A, Anand Subramony J. Engineered in-situ depot-forming hydrogels for intratumoral drug delivery. J Controlled Release. 2015;220:465\u201375.","journal-title":"J Controlled Release"},{"issue":"11","key":"2187_CR26","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1016\/j.neo.2019.09.004","volume":"21","author":"RA High","year":"2019","unstructured":"High RA, Randtke EA, Jones KM, Lindeman LR, Ma JC, Zhang S, et al. Extracellular acidosis differentiates pancreatitis and pancreatic cancer in mouse models using acidoCEST MRI. Neoplasia. 2019;21(11):1085\u201390.","journal-title":"Neoplasia"},{"key":"2187_CR27","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.toxrep.2023.06.012","volume":"11","author":"LH Zoe","year":"2023","unstructured":"Zoe LH, David SR, Rajabalaya R. Chitosan nanoparticle toxicity: A comprehensive literature review of in vivo and in vitro assessments for medical applications. Toxicol Rep. 2023;11:83\u2013106.","journal-title":"Toxicol Rep"},{"issue":"10","key":"2187_CR28","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1016\/j.fct.2005.03.007","volume":"43","author":"S Gould","year":"2005","unstructured":"Gould S, Scott RC. 2-Hydroxypropyl-\u03b2-cyclodextrin (HP-\u03b2-CD): A toxicology review. Food Chem Toxicol. 2005;43(10):1451\u20139.","journal-title":"Food Chem Toxicol"},{"issue":"11","key":"2187_CR29","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1038\/sj.bjc.6601856","volume":"90","author":"S Danson","year":"2004","unstructured":"Danson S, Ferry D, Alakhov V, Margison J, Kerr D, Jowle D, et al. Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced cancer. Br J Cancer. 2004;90(11):2085\u201391.","journal-title":"Br J Cancer"},{"key":"2187_CR30","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1080\/10915810802244595","volume":"27","author":"VCM SD S-J","year":"2008","unstructured":"SD S-J VCM. Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics. Int J Toxicol. 2008;27:93\u2013128.","journal-title":"Int J Toxicol"},{"issue":"7","key":"2187_CR31","doi-asserted-by":"publisher","first-page":"S38","DOI":"10.1016\/j.neurom.2024.06.076","volume":"27","author":"T Deer","year":"2024","unstructured":"Deer T, Hedman T, Singh H, Yu J. ID: 325486 Lumbar Intervertebral Joint Stabilization by Injectable Load-Sharing Polymers - Early Clinical Results. Neuromodulation: Technol Neural Interface. 2024;27(7):S38.","journal-title":"Neuromodulation: Technol Neural Interface"},{"issue":"17","key":"2187_CR32","doi-asserted-by":"publisher","first-page":"6307","DOI":"10.3390\/molecules28176307","volume":"28","author":"Z Cui","year":"2023","unstructured":"Cui Z, Li Z, Dong W, Qiu L, Zhang J, Wang S. Comprehensive Metabolite Identification of Genipin in Rats Using Ultra-High-Performance Liquid Chromatography Coupled with High Resolution Mass Spectrometry. Molecules. 2023;28(17):6307.","journal-title":"Molecules"},{"issue":"10","key":"2187_CR33","doi-asserted-by":"publisher","first-page":"e7287","DOI":"10.1002\/cam4.7287","volume":"13","author":"AC Larson","year":"2024","unstructured":"Larson AC, Doty KR, Solheim JC. The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer. Cancer Med. 2024;13(10):e7287.","journal-title":"Cancer Med"},{"key":"2187_CR34","doi-asserted-by":"publisher","first-page":"1199173","DOI":"10.3389\/fimmu.2023.1199173","volume":"14","author":"Y-L Yang","year":"2023","unstructured":"Yang Y-L, Yang F, Huang Z-Q, Li Y-Y, Shi H-Y, Sun Q, et al. T cells, NK cells, and tumor-associated macrophages in cancer immunotherapy and the current state of the art of drug delivery systems. Front Immunol. 2023;14:1199173.","journal-title":"Front Immunol"},{"key":"2187_CR35","doi-asserted-by":"publisher","first-page":"1656925","DOI":"10.3389\/fimmu.2025.1656925","volume":"16","author":"N Palmer","year":"2025","unstructured":"Palmer N, Khakoo S, Sanchez-Elsner T, Vallejo AF. Enhancing natural killer cell anti-tumour activity through macrophage manipulation. Front Immunol. 2025;16:1656925.","journal-title":"Front Immunol"},{"key":"2187_CR36","doi-asserted-by":"publisher","first-page":"114423","DOI":"10.1016\/j.nantod.2023.101832","volume":"50","author":"W Zhang","year":"2023","unstructured":"Zhang W, Li S, Liu Y, Xing R, Jin Z, Yan X, et al. Immunosuppressive microenvironment improvement and treatment of aggressive malignancy pancreatic ductal adenocarcinoma based on local administration of injectable hydrogel. Nano Today. 2023;50:114423.","journal-title":"Nano Today"},{"issue":"1","key":"2187_CR37","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1186\/s12951-024-02646-7","volume":"22","author":"H Zhou","year":"2024","unstructured":"Zhou H, Wang W, Cai Z, Jia Z-Y, Li Y-Y, He W, et al. Injectable hybrid hydrogels enable enhanced combination chemotherapy and roused anti-tumor immunity in the synergistic treatment of pancreatic ductal adenocarcinoma. J Nanobiotechnol. 2024;22(1):353.","journal-title":"J Nanobiotechnol"},{"issue":"2","key":"2187_CR38","doi-asserted-by":"publisher","first-page":"e001800","DOI":"10.1136\/jitc-2020-001800","volume":"9","author":"NM Mu\u00f1oz","year":"2021","unstructured":"Mu\u00f1oz 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(2):e001800.","journal-title":"J Immunother Cancer"},{"issue":"2","key":"2187_CR39","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41416-020-01048-4","volume":"124","author":"H Raskov","year":"2020","unstructured":"Raskov H, Orhan A, Christensen JP, G\u00f6genur I, Raskov H, Orhan A, et al. Cytotoxic CD8\u2009+\u2009T cells in cancer and cancer immunotherapy. Br J Cancer. 2020;124(2):359\u201367.","journal-title":"Br J Cancer"},{"issue":"10","key":"2187_CR40","doi-asserted-by":"publisher","first-page":"5637","DOI":"10.3390\/ijms23105637","volume":"23","author":"YS Cho","year":"2022","unstructured":"Cho YS. Genipin, an Inhibitor of UCP2 as a Promising New Anticancer Agent: A Review of the Literature. Int J Mol Sci. 2022;23(10):5637.","journal-title":"Int J Mol Sci"},{"issue":"9","key":"2187_CR41","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.3390\/molecules25092219","volume":"25","author":"CK Chung","year":"2020","unstructured":"Chung CK, Garc\u00eda-Couce J, Campos Y, Kralisch D, Bierau K, Chan A, et al. Doxorubicin Loaded Poloxamer Thermosensitive Hydrogels: Chemical, Pharmacological and Biological Evaluation. Molecules. 2020;25(9):2219.","journal-title":"Molecules"},{"issue":"2","key":"2187_CR42","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.gie.2011.08.049","volume":"75","author":"MJ Hewitt","year":"2012","unstructured":"Hewitt MJ, McPhail MJ, Possamai L, Dhar A, Vlavianos P, Monahan KJ. EUS-guided FNA for diagnosis of solid pancreatic neoplasms: a meta-analysis. Gastrointest Endosc. 2012;75(2):319\u201331.","journal-title":"Gastrointest Endosc"},{"issue":"21","key":"2187_CR43","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.3748\/wjg.v28.i21.2383","volume":"28","author":"J Kaur","year":"2022","unstructured":"Kaur J, Jaruvongvanich V, Chandrasekhara V. Endoscopic ultrasound-guided injectable therapy for pancreatic cancer: A systematic review. World J Gastroenterol. 2022;28(21):2383.","journal-title":"World J Gastroenterol"},{"issue":"24","key":"2187_CR44","doi-asserted-by":"publisher","first-page":"5801","DOI":"10.3390\/cancers15245801","volume":"15","author":"J Lazarovits","year":"2023","unstructured":"Lazarovits J, Epelbaum R, Lachter J, Amikam Y, Arie JB, Lazarovits J, et al. Multisite Is Superior to Single-Site Intratumoral Chemotherapy to Retard the Outcomes of Pancreatic Ductal Adenocarcinoma in a Murine Model. Cancers. 2023;15(24):5801.","journal-title":"Cancers"},{"key":"2187_CR45","unstructured":"V E, vD JL, S M, J QP, G K, A-V JM, et al. Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin Oncol. 2022;40(11)."},{"issue":"3","key":"2187_CR46","doi-asserted-by":"publisher","first-page":"e179","DOI":"10.1097\/MPA.0000000000002236","volume":"52","author":"NR Sharma","year":"2023","unstructured":"Sharma NR, Lo SK, Hendifar A, Othman MO, Patel K, Mendoza-Ladd A, et al. Response of Locally Advanced Pancreatic Cancer to Intratumoral Injection of Large Surface Area Microparticle Paclitaxel: Initial Report of Safety and Clinical Outcome. Pancreas. 2023;52(3):e179\u201387.","journal-title":"Pancreas"},{"issue":"1","key":"2187_CR47","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1186\/s12885-018-4453-z","volume":"18","author":"Y Hirooka","year":"2018","unstructured":"Hirooka Y, Kasuya H, Ishikawa T, Kawashima H, Ohno E, Villalobos IB, Naoe Y, Ichinose T, Koyama N, Tanaka M, Kodera Y. A Phase I clinical trial of EUS-guided intratumoral injection of the oncolytic virus, HF10 for unresectable locally advanced pancreatic cancer. BMC Cancer. 2018;18(1):596.","journal-title":"BMC Cancer"},{"key":"2187_CR48","doi-asserted-by":"crossref","unstructured":"Stoop TF, Theijse RT, Seelen LWF, Groot Koerkamp B, van Eijck CHJ, Wolfgang CL, et al. Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer. Nat Reviews Gastroenterol Hepatol. 2023;21(2).","DOI":"10.1038\/s41575-023-00856-2"},{"issue":"2","key":"2187_CR49","doi-asserted-by":"publisher","first-page":"C540","DOI":"10.1152\/ajpcell.00331.2022","volume":"324","author":"AK Beutel","year":"2023","unstructured":"Beutel AK, Halbrook CJ. Barriers and opportunities for gemcitabine in pancreatic cancer therapy. Am J Physiology-Cell Physiol. 2023;324(2):C540\u201352.","journal-title":"Am J Physiology-Cell Physiol"},{"issue":"2","key":"2187_CR50","doi-asserted-by":"publisher","first-page":"e001191","DOI":"10.1136\/jitc-2020-001191","volume":"8","author":"C Groeneveldt","year":"2020","unstructured":"Groeneveldt C, Kinderman P, Wollenberg DJMvd O, RLvd, Middelburg J, Mustafa DAM, et al. Preconditioning of the tumor microenvironment with oncolytic reovirus converts CD3-bispecific antibody treatment into effective immunotherapy. J Immunother Cancer. 2020;8(2):e001191.","journal-title":"J Immunother Cancer"},{"key":"2187_CR51","doi-asserted-by":"publisher","first-page":"5205","DOI":"10.2147\/OTT.S322276","volume":"14","author":"MJA Schoonderwoerd","year":"2021","unstructured":"Schoonderwoerd MJA, Hakuno SK, Sassen M, Kuhlemaijer EB, Paauwe M, Slingerland M, et al. Targeting Endoglin Expressing Cells in the Tumor Microenvironment Does Not Inhibit Tumor Growth in a Pancreatic Cancer Mouse Model. OncoTargets Therapy. 2021;14:5205\u201320.","journal-title":"OncoTargets Therapy"},{"issue":"1","key":"2187_CR52","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.cell.2014.12.021","volume":"160","author":"SF Boj","year":"2015","unstructured":"Boj SF, Hwang CI, Baker LA, Chio II, Engle DD, Corbo V, Jager M, Ponz-Sarvise M, Tiriac H, Spector MS, Gracanin A. Organoid models of human and mouse ductal pancreatic cancer. Cell. 2015;160(1):324\u201338.","journal-title":"Cell"},{"issue":"4","key":"2187_CR53","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.gastha.2022.04.019","volume":"1","author":"TJ Harryvan","year":"2022","unstructured":"Harryvan TJ, Hawinkels LJAC, \u00d6stman A, Dijke Pt, Strell C, Hornsveld M. A Novel Pancreatic Cancer Mini-tumor Model to Study Desmoplasia and Myofibroblastic Cancer-Associated Fibroblast Differentiation. Gastro Hep Adv. 2022;1(4):678\u201381.","journal-title":"Gastro Hep Adv"},{"issue":"1","key":"2187_CR54","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1179\/his.2004.27.1.31","volume":"27","author":"E Rossomacha","year":"2004","unstructured":"Rossomacha E, Hoemanni CD, Shive MS. Simple Methods for Staining Chitosan in Biotechnological Applications. J Histotechnology. 2004;27(1):31\u20136.","journal-title":"J Histotechnology"},{"key":"2187_CR55","doi-asserted-by":"crossref","unstructured":"Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7).","DOI":"10.1038\/nmeth.2019"}],"container-title":["Drug Delivery and Translational Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-026-02187-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13346-026-02187-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-026-02187-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T22:01:15Z","timestamp":1784412075000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13346-026-02187-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,18]]},"references-count":55,"alternative-id":["2187"],"URL":"https:\/\/doi.org\/10.1007\/s13346-026-02187-6","relation":{},"ISSN":["2190-393X","2190-3948"],"issn-type":[{"value":"2190-393X","type":"print"},{"value":"2190-3948","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,18]]},"assertion":[{"value":"12 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"H.M.K is a named inventor on granted patent US20230126053 \u2018Thermo-responsive hydrogel for intratumoral administration as a treatment in solid tumor cancers\u2019 and is also co-founder and CSO of OncoLize LLC. M.G.W.L. is co-founder and CEO of OncoLize LLC. T.T. is drug development director of OncoLize LLC. L.J.A.C.H receives consultancy fees from InnoSer BioSciences and has supported grants from Tracon Pharmaceuticals (not related to this work). This work was supported by a research grant from OncoLize to L.J.A.C.H.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}