{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T17:03:16Z","timestamp":1790528596878,"version":"4.1.0"},"reference-count":144,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T00:00:00Z","timestamp":1577750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nanoparticle-based radiosensitization of cancerous cells is evolving as a favorable modality for enhancing radiotherapeutic ratio, and as an effective tool for increasing the outcome of concomitant chemoradiotherapy. Nevertheless, delivery of sufficient concentrations of nanoparticles (NPs) or nanoparticle-based radiosensitizers (NBRs) to the targeted tumor without or with limited systemic side effects on healthy tissues\/organs remains a challenge that many investigators continue to explore. With current systemic intravenous delivery of a drug, even targeted nanoparticles with great prospect of reaching targeted distant tumor sites, only a portion of the administered NPs\/drug dosage can reach the tumor, despite the enhanced permeability and retention (EPR) effect. The rest of the targeted NPs\/drug remain in systemic circulation, resulting in systemic toxicity, which can decrease the general health of patients. However, the dose from ionizing radiation is generally delivered across normal tissues to the tumor cells (especially external beam radiotherapy), which limits dose escalation, making radiotherapy (RT) somewhat unsafe for some diseased sites despite the emerging development in RT equipment and technologies. Since radiation cannot discriminate healthy tissue from diseased tissue, the radiation doses delivered across healthy tissues (even with nanoparticles delivered via systemic administration) are likely to increase injury to normal tissues by accelerating DNA damage, thereby creating free radicals that can result in secondary tumors. As a result, other delivery routes, such as inhalation of nanoparticles (for lung cancers), localized delivery via intratumoral injection, and implants loaded with nanoparticles for local radiosensitization, have been studied. Herein, we review the current NP delivery techniques; precise systemic delivery (injection\/infusion and inhalation), and localized delivery (intratumoral injection and local implants) of NBRs\/NPs. The current challenges, opportunities, and future prospects for delivery of nanoparticle-based radiosensitizers are also discussed.<\/jats:p>","DOI":"10.3390\/ijms21010273","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T03:28:53Z","timestamp":1578022133000},"page":"273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["Delivery of Nanoparticle-Based Radiosensitizers for Radiotherapy Applications"],"prefix":"10.3390","volume":"21","author":[{"given":"Francis","family":"Boateng","sequence":"first","affiliation":[{"name":"TIDTAC LLC, Orlando, FL 32828, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred","family":"Ngwa","sequence":"additional","affiliation":[{"name":"TIDTAC LLC, Orlando, FL 32828, USA"},{"name":"Department of Physics and Applied Physics, University of Massachusetts Lowell Lowell, MA 01854, USA"},{"name":"Department of Radiation Oncology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Radiation Oncology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3389\/fonc.2017.00208","article-title":"Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids","volume":"7","author":"Ngwa","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_2","unstructured":"Boateng, F. (2017). In Silico Study of Smart Radiotherapy Biomaterials for Radiotherapy Applications, University of Massachusetts Lowell, ProQuest Dissertations Publishing."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20150171","DOI":"10.1259\/bjr.20150171","article-title":"The Future of Nanosized Radiation Enhancers","volume":"88","author":"Pottier","year":"2015","journal-title":"Br. J. Radiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.ijrobp.2016.10.034","article-title":"Smart Radiation Therapy Biomaterials","volume":"97","author":"Ngwa","year":"2017","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/S1470-2045(15)00222-3","article-title":"Expanding global access to radiotherapy","volume":"16","author":"Atun","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_6","first-page":"187s","article-title":"Radiation sensitizers: A selective review of molecules targeting DNA and non-DNA targets","volume":"46","author":"Kvols","year":"2005","journal-title":"J. Nucl. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13046-018-0758-7","article-title":"Role of metabolism in cancer cell radioresistance and radiosensitization methods","volume":"37","author":"Tang","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_8","first-page":"330","article-title":"Nanoparticles in radiation therapy: A summary of various approaches to enhance radiosensitization in cancer","volume":"2","author":"Kwatra","year":"2013","journal-title":"Transl. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4518","DOI":"10.1021\/am506866a","article-title":"Enhanced radiation therapy with multilayer microdisks containing radiosensitizing gold nanoparticles","volume":"7","author":"Zhang","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/978-1-4939-6646-2_25","article-title":"Nanoparticle-Mediated X-Ray Radiation Enhancement for Cancer Therapy","volume":"1530","author":"Paro","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s11604-017-0671-6","article-title":"Capacity of gold nanoparticles in cancer radiotherapy","volume":"35","author":"Nagi","year":"2017","journal-title":"Jpn. J. Radiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e005633","DOI":"10.1161\/JAHA.117.005633","article-title":"Long-Term Cardiovascular Risk After Radiotherapy in Women with Breast Cancer","volume":"6","author":"Cheng","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.semradonc.2007.10.009","article-title":"Targeted molecular imaging in oncology: Focus on radiation therapy","volume":"18","author":"Nimmagadda","year":"2008","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1097\/PPO.0b013e318292e4e3","article-title":"Basic mechanisms of therapeutic resistance to radiation and chemotherapy in lung cancer","volume":"19","author":"Willers","year":"2013","journal-title":"Cancer J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20170069","DOI":"10.1259\/bjr.20170069","article-title":"Modeling Gold Nanoparticle-Eluting Spacer Degradation during Brachytherapy Application with in situ Dose-painting","volume":"90","author":"Boateng","year":"2017","journal-title":"Br. J. Radiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1021\/nn900002m","article-title":"Impact of nanotechnology on drug delivery","volume":"3","author":"Farokhzad","year":"2009","journal-title":"ACS Nano"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.tips.2017.11.003","article-title":"Cancer Radiosensitizers","volume":"39","author":"Wang","year":"2018","journal-title":"Trends Pharm. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6533","DOI":"10.1088\/0031-9155\/55\/21\/013","article-title":"Applying gold nanoparticles as tumor-vascular disrupting agents during brachytherapy: Estimation of endothelial dose enhancement","volume":"55","author":"Ngwa","year":"2010","journal-title":"Phys. Med. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1118\/1.3671905","article-title":"Gold nanoparticle-aided brachytherapy with vascular dose painting: Estimation of dose enhancement to the tumor endothelial cell nucleus","volume":"39","author":"Ngwa","year":"2012","journal-title":"Med. Phys."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.2217\/nnm.14.55","article-title":"Targeted radiotherapy with gold nanoparticles: Current status and future perspectives","volume":"9","author":"Ngwa","year":"2014","journal-title":"Nanomedicine (Lond)"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejmp.2014.11.004","article-title":"New potential for enhancing concomitant chemoradiotherapy with FDA approved concentrations of cisplatin via the photoelectric effect","volume":"31","author":"Altundal","year":"2015","journal-title":"Phys. Med."},{"key":"ref_22","unstructured":"Jaffray, A.D. (2015, January 7\u201312). Dose enhancement during concomitant chemoradiotherapy using FDA approved concentrations of carboplatin and oxaliplatin nanoparticles. Proceedings of the World Congress on Medical Physics and Biomedical Engineering, Toronto, ON, Canada."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3389\/fchem.2014.00086","article-title":"Gold nanoparticles and their alternatives for radiation therapy enhancement","volume":"2","author":"Cooper","year":"2014","journal-title":"Front. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hildenbrand, G., Metzler, P., Pilarczyk, G., Bobu, V., Kriz, W., Hosser, H., Fleckenstein, J., Krufczik, M., Bestvater, F., and Wenz, F. (2018). Dose enhancement effects of gold nanoparticles specifically targeting RNA in breast cancer cells. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0190183"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12645-017-0026-0","article-title":"Biological mechanisms of gold nanoparticle radiosensitization","volume":"8","author":"Rosa","year":"2017","journal-title":"Cancer Nanotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20140134","DOI":"10.1259\/bjr.20140134","article-title":"The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy","volume":"87","author":"Sancey","year":"2014","journal-title":"Br. J. Radiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1021\/cs200208a","article-title":"Catalytic Activity of Faceted Gold Nanoparticles Studied by a Model Reaction: Evidence for Substrate-Induced Surface Restructuring","volume":"1","author":"Wunder","year":"2011","journal-title":"ACS Catal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1211\/jpp.60.8.0001","article-title":"Mechanism of radiation-induced bystander effects: A unifying model","volume":"60","author":"Hei","year":"2008","journal-title":"J. Pharm. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"215101","DOI":"10.1088\/0957-4484\/27\/21\/215101","article-title":"Protein disulphide isomerase as a target for nanoparticle-mediated sensitisation of cancer cells to radiation","volume":"27","author":"Taggart","year":"2016","journal-title":"Nanotechnology"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Guo, M., Sun, Y., and Zhang, X.-D. (2017). Enhanced Radiation Therapy of Gold Nanoparticles in Liver Cancer. Appl. Sci., 7.","DOI":"10.3390\/app7030232"},{"key":"ref_31","unstructured":"Kumar, R., Korideck, H., Ngwa, W., Berbeco, R.I., Makrigiorgos, G.M., and Sridhar, S. (2013). Third generation gold nanoplatform optimized for radiation therapy. Transl. Cancer Res., 2."},{"key":"ref_32","first-page":"026","article-title":"Gold Nanoparticles for Radiation Enhancement in Vivo","volume":"3","author":"Shrestha","year":"2016","journal-title":"Jacobs, J. Radiat. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.7150\/thno.22172","article-title":"Metal-based Nano Enhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells","volume":"8","author":"Liu","year":"2018","journal-title":"Theranostics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1118\/1.1797531","article-title":"Dose enhancement close to platinum implants for the 4, 6, and 10 MV stereotactic radiosurgery","volume":"31","author":"Cheung","year":"2004","journal-title":"Med. Phys."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/01.HP.0000264450.81683.51","article-title":"The calculation of dose enhancement close to platinum implants for skull radiography","volume":"93","author":"Cheung","year":"2007","journal-title":"Health Phys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1211\/jpp.60.8.0005","article-title":"Radiotherapy enhancement with gold nanoparticles","volume":"60","author":"Hainfeld","year":"2008","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Cappellano, G., Comi, C., Chiocchetti, A., and Dianzani, U. (2019). Exploiting PLGA-Based Biocompatible Nanoparticles for Next-Generation Tolerogenic Vaccines against Autoimmune Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010204"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41392-017-0004-3","article-title":"Controlled drug delivery vehicles for cancer treatment and their performance","volume":"3","author":"Senapati","year":"2018","journal-title":"Signal Transduct. Target."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Maiti, S., and Sen, K.K. (2017). Introductory Chapter: Drug Delivery Concepts, Advanced Technology for Delivering Therapeutics. IntechOpen.","DOI":"10.5772\/65245"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"126","DOI":"10.4103\/0972-124X.60224","article-title":"Evaluation of two local drug delivery systems as adjuncts to mechanotherapy as compared to mechanotherapy alone in management of chronic periodontitis: A clinical, microbiological, and molecular study","volume":"13","author":"Singh","year":"2009","journal-title":"J. Indian Soc. Periodontol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1158\/1078-0432.CCR-17-3811","article-title":"Enhanced Intratumoral Delivery of SN38 as a Tocopherol Oxyacetate Prodrug Using Nanoparticles in a Neuroblastoma Xenograft Model","volume":"24","author":"Nguyen","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_42","first-page":"2479","article-title":"Recent developments in radiosensitization","volume":"35","author":"Linam","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1801806","DOI":"10.1002\/advs.201801806","article-title":"Enhanced Radiosensitization by Gold Nanoparticles with Acid-Triggered Aggregation in Cancer Radiotherapy","volume":"6","author":"Zhang","year":"2019","journal-title":"Adv. Sci. (Weinh)"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"20180745","DOI":"10.1259\/bjr.20180745","article-title":"Novel Bioerodable Eluting-Spacers for Radiotherapy Applications with in Situ Dose Painting","volume":"92","author":"Boateng","year":"2019","journal-title":"Br. J. Radiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.ijrobp.2014.10.001","article-title":"Brachytherapy application with in situ dose painting administered by gold nanoparticle eluters","volume":"91","author":"Sinha","year":"2015","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0169-409X(02)00050-9","article-title":"Polyanhydrides: An overview","volume":"54","author":"Kumar","year":"2002","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"ref_47","first-page":"3194","article-title":"New Designed Radiotherapy Biomaterials with Reservoir and Coated Spacers for Radiotherapy Applications: WE-AB-605-10","volume":"44","author":"Boateng","year":"2017","journal-title":"Med. Phys."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.ijrobp.2009.06.039","article-title":"Biological in situ dose painting for image-guided radiation therapy using drug-loaded implantable devices","volume":"76","author":"Cormack","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4103\/2230-973X.96920","article-title":"Drug delivery systems: An updated review","volume":"2","author":"Tiwari","year":"2012","journal-title":"Int. J. Pharm. Investig."},{"key":"ref_50","first-page":"64","article-title":"Applications of nanoparticle systems in drug delivery technology","volume":"26","author":"Rizvi","year":"2018","journal-title":"Saudi Pharm. J. Spj Off. Publ. Saudi Pharm. Soc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.3109\/10717544.2014.948643","article-title":"Development and evaluation of carboplatin-loaded PCL nanoparticles for intranasal delivery","volume":"23","author":"Alex","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jconrel.2010.08.027","article-title":"To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery","volume":"148","author":"Danhier","year":"2010","journal-title":"J. Control. Releas"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2217\/nnm.12.87","article-title":"Nanotechnology in therapeutics: A focus on nanoparticles as a drug delivery system","volume":"7","author":"Bamrungsap","year":"2012","journal-title":"Nanomedicine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1158\/1535-7163.MCT-06-0141","article-title":"Nanotechnology in cancer therapeutics: Bioconjugated nanoparticles for drug delivery","volume":"5","author":"Sinha","year":"2006","journal-title":"Mol. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/s41467-018-03705-y","article-title":"Progress and challenges towards targeted delivery of cancer therapeutics","volume":"9","author":"Rosenblum","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-642-00477-3_1","article-title":"Passive and active drug targeting: Drug delivery to tumors as an example","volume":"197","author":"Torchilin","year":"2010","journal-title":"Handb. Exp. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jconrel.2011.06.001","article-title":"Targeted drug delivery to tumors: Myths, reality and possibility","volume":"153","author":"Bae","year":"2011","journal-title":"J. Control Release"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7504","DOI":"10.1039\/C7TB01142C","article-title":"Enhanced cell uptake of fluorescent drug-loaded nanoparticles via an implantable photothermal fibrous patch for more effective cancer cell killing","volume":"5","author":"Li","year":"2017","journal-title":"J. Mater. Chem. B"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15549","DOI":"10.1073\/pnas.0707461104","article-title":"Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging","volume":"104","author":"Bartlett","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e29528","DOI":"10.4161\/tisb.29528","article-title":"Barriers to drug delivery in solid tumors","volume":"2","author":"Sriraman","year":"2014","journal-title":"Tissue Barriers"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1021\/acscentsci.6b00190","article-title":"Does Nanomedicine Have a Delivery Problem?","volume":"2","author":"Torrice","year":"2016","journal-title":"ACS Cent. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1073\/pnas.0909611107","article-title":"DNA aptamer-micelle as an efficient detection\/delivery vehicle toward cancer cells","volume":"107","author":"Wu","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3109\/09687688.2010.510804","article-title":"Nanoparticulate drug delivery systems for cancer chemotherapy","volume":"27","author":"Saha","year":"2010","journal-title":"Mol. Membr. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"17356","DOI":"10.1073\/pnas.0809154105","article-title":"Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles","volume":"105","author":"Dhar","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.nano.2015.10.018","article-title":"Advances in silica based nanoparticles for targeted cancer therapy","volume":"12","author":"Yang","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"681","DOI":"10.12688\/f1000research.9690.1","article-title":"Nanoparticle-based drug delivery systems: What can they really do in vivo?","volume":"6","author":"Wang","year":"2017","journal-title":"F1000Research"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/nrc1456","article-title":"High interstitial fluid pressure - an obstacle in cancer therapy","volume":"4","author":"Heldin","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7035","DOI":"10.1088\/0031-9155\/60\/18\/7035","article-title":"Potential for enhancing external beam radiotherapy for lung cancer using high-Z nanoparticles administered via inhalation","volume":"60","author":"Hao","year":"2015","journal-title":"Phys. Med. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3389\/fonc.2011.00052","article-title":"Phase I study of celecoxib with concurrent irinotecan, Cisplatin, and radiation therapy for patients with unresectable locally advanced non-small cell lung cancer","volume":"1","author":"Komaki","year":"2011","journal-title":"Front. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3874","DOI":"10.1118\/1.2349696","article-title":"The management of respiratory motion in radiation oncology report of AAPM Task Group 76","volume":"33","author":"Keall","year":"2006","journal-title":"Med. Phys."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1118\/1.1915017","article-title":"Dosimetric impact of geometric errors due to respiratory motion prediction on dynamic multileaf collimator-based four-dimensional radiation delivery","volume":"32","author":"Vedam","year":"2005","journal-title":"Med. Phys."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1118\/1.2192908","article-title":"Dosimetric and radiobiological impact of dose fractionation on respiratory motion induced IMRT delivery errors: A volumetric dose measurement study","volume":"33","author":"Duan","year":"2006","journal-title":"Med. Phys."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"900","DOI":"10.3109\/1061186X.2011.622404","article-title":"Innovative strategy for treatment of lung cancer: Targeted nanotechnology-based inhalation co-delivery of anticancer drugs and siRNA","volume":"19","author":"Taratula","year":"2011","journal-title":"J. Drug Target."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1007\/s11095-010-0360-y","article-title":"Intratumoral drug delivery with nanoparticulate carriers","volume":"28","author":"Holback","year":"2011","journal-title":"Pharm. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"16014","DOI":"10.1038\/natrevmats.2016.14","article-title":"Analysis of nanoparticle delivery to tumours","volume":"1","author":"Wilhelm","year":"2016","journal-title":"Nat. Rev. Mater."},{"key":"ref_76","first-page":"82","article-title":"Local Drug Delivery Systems in the Treatment of Periodontitis: A Literature Review","volume":"17","author":"Silva","year":"2015","journal-title":"J. Int. Acad. Periodontol."},{"key":"ref_77","first-page":"39","article-title":"Biodegradable polymers in controlled drug delivery","volume":"1","author":"Heller","year":"1984","journal-title":"Crit. Rev. Ther. Drug Carrier Syst."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1593\/neo.06436","article-title":"Effect of intratumoral injection on the biodistribution and the therapeutic potential of HPMA copolymer-based drug delivery systems","volume":"8","author":"Lammers","year":"2006","journal-title":"Neoplasia (New York N. Y.)"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1227\/00006123-199512000-00013","article-title":"Intratumoral chemotherapy","volume":"37","author":"Walter","year":"1995","journal-title":"Neurosurgery"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1097\/00000421-200202000-00013","article-title":"Intratumoral doxorubicin in patients with malignant brain gliomas","volume":"25","author":"Voulgaris","year":"2002","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1211\/0022357021778268","article-title":"Intratumoral cancer chemotherapy and immunotherapy: Opportunities for nonsystemic preoperative drug delivery","volume":"54","author":"Goldberg","year":"2002","journal-title":"J. Pharm. Pharm."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1177\/000348940411300312","article-title":"Phase 2 study of intratumoral cisplatin and epinephrine treatment for locally recurrent head and neck tumors","volume":"113","author":"Duvillard","year":"2004","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"689","DOI":"10.2147\/IJN.S188667","article-title":"Improving antitumor outcomes for palliative intratumoral injection therapy through lecithin- chitosan nanoparticles loading paclitaxel- cholesterol complex","volume":"14","author":"Chu","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jconrel.2009.10.003","article-title":"Pharmacokinetics of doxorubicin after intratumoral injection using a thermosensitive hydrogel in tumor-bearing mice","volume":"142","author":"Hong","year":"2010","journal-title":"J. Control Release"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.colsurfb.2018.03.009","article-title":"Intratumoral administration of carboplatin bearing poly (\u03b5-caprolactone) nanoparticles amalgamated with in situ gel tendered augmented drug delivery, cytotoxicity, and apoptosis in melanoma tumor","volume":"166","author":"Bragta","year":"2018","journal-title":"Colloids Surf. B: Biointerfaces"},{"key":"ref_86","first-page":"1892","article-title":"Effects of 90Y-microspheres on liver tumors: Comparison of intratumoral injection method and intra-arterial injection method","volume":"41","author":"Lin","year":"2000","journal-title":"J. Nucl. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ejpb.2008.10.015","article-title":"Ultrafine PEG-PLA fibers loaded with both paclitaxel and doxorubicin hydrochloride and their in vitro cytotoxicity","volume":"72","author":"Xu","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_88","first-page":"1121","article-title":"Direct percutaneous intratumoral bleomycin injection for palliative treatment of impending quadriplegia","volume":"25","author":"Duncan","year":"2004","journal-title":"Ajnr Am. J. Neuroradiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/CAD.0b013e328012bccd","article-title":"Intratumoral delivery of paclitaxel-loaded poly(lactic-co-glycolic acid) microspheres for Hep-2 laryngeal squamous cell carcinoma xenografts","volume":"18","author":"Xie","year":"2007","journal-title":"Anticancer Drugs"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1097\/MNM.0000000000000792","article-title":"Intratumoral injection of radioactive holmium-166 microspheres in recurrent head and neck squamous cell carcinoma: Preliminary results of first use","volume":"39","author":"Bakker","year":"2018","journal-title":"Nucl. Med. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1177\/019459989811800412","article-title":"Intratumoral cisplatin\/epinephrine-injectable gel as a palliative treatment for accessible solid tumors: A multicenter pilot study","volume":"118","author":"Burris","year":"1998","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.lungcan.2015.10.009","article-title":"Treatment of isolated mediastinal and hilar recurrence of lung cancer with bronchoscopic endobronchial ultrasound guided intratumoral injection of chemotherapy with cisplatin","volume":"90","author":"Mehta","year":"2015","journal-title":"Lung Cancer"},{"key":"ref_93","first-page":"e54855","article-title":"Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer","volume":"12","author":"Mehta","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.2174\/138161212800626229","article-title":"Chemoradiotherapy of human tumors: Novel approaches from nanomedicine","volume":"18","author":"Werner","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"239","DOI":"10.4155\/tde.12.147","article-title":"Nanomedicine in chemoradiation","volume":"4","author":"Miller","year":"2013","journal-title":"Ther. Deliv."},{"key":"ref_96","first-page":"320","article-title":"Improving chemoradiotherapy with nanoparticle therapeutics","volume":"2","author":"Eblan","year":"2013","journal-title":"Transl. Cancer Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"791","DOI":"10.4155\/tde-2017-0043","article-title":"Applying nanotherapeutics to improve chemoradiotherapy treatment for cancer","volume":"8","author":"Caster","year":"2017","journal-title":"Ther. Deliv."},{"key":"ref_98","first-page":"131","article-title":"Hydrolytic Degradation Behavior of 50-50 Poly Lactide-co-Glycolide from Drug. Trends Biomater","volume":"24","author":"Engineer","year":"2010","journal-title":"Artif. Organs"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ijpharm.2010.12.020","article-title":"Modeling of drug release from bulk-degrading polymers","volume":"418","author":"Lao","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/1097-4636(20010615)55:4<512::AID-JBM1044>3.0.CO;2-N","article-title":"Fabrication and characterization of controlled release poly(D,L-lactide-co-glycolide) millirods","volume":"55","author":"Qian","year":"2001","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1158\/1078-0432.CCR-08-1691","article-title":"Intratumoral delivery of beta-lapachone via polymer implants for prostate cancer therapy","volume":"15","author":"Dong","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jconrel.2004.04.011","article-title":"In vitro study of release mechanisms of paclitaxel and rapamycin from drug-incorporated biodegradable stent matrices","volume":"98","author":"Alexis","year":"2004","journal-title":"J. Control Release"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jconrel.2011.11.031","article-title":"Local drug delivery strategies for cancer treatment: Gels, nanoparticles, polymeric films, rods, and wafers","volume":"159","author":"Wolinsky","year":"2012","journal-title":"J. Control Release"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ijrobp.2014.10.041","article-title":"Nanoparticle-based brachytherapy spacers for delivery of localized combined chemoradiation therapy","volume":"91","author":"Kumar","year":"2015","journal-title":"Int. J. Radiat Oncol. Biol. Phys."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3389\/fonc.2018.00056","article-title":"Priming the Abscopal Effect Using Multifunctional Smart Radiotherapy Biomaterials Loaded with Immunoadjuvants","volume":"8","author":"Moreau","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"6039","DOI":"10.1088\/0031-9155\/55\/20\/001","article-title":"Radiosensitizer-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT)","volume":"55","author":"Nagesha","year":"2010","journal-title":"Phys. Med. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.1088\/0031-9155\/56\/17\/001","article-title":"Treatment precision of image-guided liver SBRT using implanted fiducial markers depends on marker-tumour distance","volume":"56","author":"Seppenwoolde","year":"2011","journal-title":"Phys. Med. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1754-9485.2012.02445.x","article-title":"Planting the seeds of success: CT-guided gold seed fiducial marker placement to guide robotic radiosurgery","volume":"57","author":"Patel","year":"2013","journal-title":"J. Med. Imaging Radiat Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/bju.12624","article-title":"Fiducial markers and spacers in prostate radiotherapy: Current applications","volume":"113","author":"Ng","year":"2014","journal-title":"BJU Int."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"S856","DOI":"10.1016\/j.ijrobp.2014.05.2450","article-title":"Radiation Therapy Biomaterials for Response Assessment and Nodal Detection (Brand)","volume":"90","author":"Ngwa","year":"2014","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1118\/1.4923919","article-title":"SU-D-210-04: Using Radiotherapy Biomaterials to Brand and Track Deadly Cancer Cells","volume":"42","author":"Altundal","year":"2015","journal-title":"Med Phys."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.3390\/cancers5041691","article-title":"Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo","volume":"5","author":"Galanzha","year":"2013","journal-title":"Cancers"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"056014","DOI":"10.1117\/1.JBO.19.5.056014","article-title":"Detection of circulating tumor cells using targeted surface-enhanced Raman scattering nanoparticles and magnetic enrichment","volume":"19","author":"Shi","year":"2014","journal-title":"J. Biomed. Opt."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/(SICI)1098-2825(1999)13:5<229::AID-JCLA7>3.0.CO;2-Y","article-title":"Detection of circulating melanoma cells by immunomagnetic cell sorting","volume":"13","author":"Benez","year":"1999","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"5044","DOI":"10.1158\/0008-5472.CAN-04-1058","article-title":"In Vivo Flow Cytometry a New Method for Enumerating Circulating Cancer Cells","volume":"64","author":"Georgakoudi","year":"2004","journal-title":"Cancer Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1016\/j.bios.2005.12.024","article-title":"High speed detection of circulating tumor cells","volume":"21","author":"Hsieh","year":"2006","journal-title":"Biosens. Bioelectron."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2998","DOI":"10.1364\/OL.31.002998","article-title":"Photoacoustic detection of metastatic melanoma cells in the human circulatory system","volume":"31","author":"Weight","year":"2006","journal-title":"Opt. Lett."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1021\/nl052396o","article-title":"Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells","volume":"6","author":"Chithrani","year":"2006","journal-title":"Nano Lett."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"17214","DOI":"10.1021\/ja804494m","article-title":"Surface-enhanced Raman scattering tags for rapid and homogeneous detection of circulating tumor cells in the presence of human whole blood","volume":"130","author":"Sha","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.canlet.2014.02.006","article-title":"Gold nanoparticles in breast cancer treatment: Promise and potential pitfalls","volume":"347","author":"Lee","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"7500","DOI":"10.1021\/nn401095p","article-title":"High-resolution cellular MRI: Gadolinium and iron oxide nanoparticles for in-depth dual-cell imaging of engineered tissue constructs","volume":"7","author":"Gazeau","year":"2013","journal-title":"ACS Nano"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1166\/jbn.2010.1105","article-title":"Gold nanoparticle mediated detection of prostate cancer cells using photoacoustic flowmetry with optical reflectance","volume":"6","author":"Viator","year":"2010","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"064701","DOI":"10.1063\/1.2777127","article-title":"Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging","volume":"102","author":"Agarwal","year":"2007","journal-title":"J. Appl. Phys."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"617421","DOI":"10.1155\/2010\/617421","article-title":"Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer","volume":"2010","author":"Miller","year":"2010","journal-title":"J. Oncol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.jconrel.2013.09.013","article-title":"Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles","volume":"172","author":"Ernsting","year":"2013","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jconrel.2017.08.003","article-title":"Nano-sized drug carriers: Extravasation, intratumoral distribution, and their modeling","volume":"267","author":"Nichols","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.7150\/thno.11742","article-title":"Current Approaches for Improving Intratumoral Accumulation and Distribution of Nanomedicines","volume":"5","author":"Durymanov","year":"2015","journal-title":"Theranostics"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0378-5173(99)00432-9","article-title":"Nanoparticles with decreasing surface hydrophobicities: Influence on plasma protein adsorption","volume":"196","author":"Gessner","year":"2000","journal-title":"Int. J. Pharm."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1016\/j.biomaterials.2006.10.002","article-title":"In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: Mechanisms, key factors, and their implications","volume":"28","author":"Cho","year":"2007","journal-title":"Biomaterials"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1021\/acs.biomac.7b00068","article-title":"Enhancing Tumor Penetration of Nanomedicines","volume":"18","author":"Sun","year":"2017","journal-title":"Biomacromolecules"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1158\/1078-0432.CCR-08-2392","article-title":"Tumor-targeted nanomedicines: Enhanced antitumor efficacy in vivo of doxorubicin-loaded, long-circulating liposomes modified with cancer-specific monoclonal antibody","volume":"15","author":"ElBayoumi","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"6315","DOI":"10.1073\/pnas.0601755103","article-title":"Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo","volume":"103","author":"Farokhzad","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1002\/smll.200700794","article-title":"Enhancement of radiation cytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles","volume":"4","author":"Kong","year":"2008","journal-title":"Small"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Aguilar, Z.P. (2013). Chapter 5-Targeted Drug Delivery. Nanomaterials for Medical Applications, Elsevier.","DOI":"10.1016\/B978-0-12-385089-8.00005-4"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"11417","DOI":"10.1002\/anie.201104449","article-title":"Fluorescent nanorods and nanospheres for real-time in vivo probing of nanoparticle shape-dependent tumor penetration","volume":"50","author":"Chauhan","year":"2011","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"952","DOI":"10.3389\/fphar.2017.00952","article-title":"Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery","volume":"8","author":"Zhang","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"62607","DOI":"10.18632\/oncotarget.11546","article-title":"Optimization of the tumor microenvironment and nanomedicine properties simultaneously to improve tumor therapy","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0378-5173(99)00060-5","article-title":"A method using biodegradable polylactides\/polyethylene glycol for drug release with reduced initial burst","volume":"182","author":"Huang","year":"1999","journal-title":"Int. J. Pharm."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0168-3659(01)00248-6","article-title":"On the importance and mechanisms of burst release in matrix-controlled drug delivery systems","volume":"73","author":"Huang","year":"2001","journal-title":"J. Control Release"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF02980037","article-title":"Control of encapsulation efficiency and initial burst in polymeric microparticle systems","volume":"27","author":"Yeo","year":"2004","journal-title":"Arch. Pharm. Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1081\/DDC-43985","article-title":"Reduction in the initial-burst release by surface crosslinking of PLGA microparticles containing hydrophilic or hydrophobic drugs","volume":"31","author":"Thote","year":"2005","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3109\/10837450.2010.513989","article-title":"Reduction in burst release after coating poly(D,L-lactide-co-glycolide) (PLGA) microparticles with a drug-free PLGA layer","volume":"17","author":"Ahmed","year":"2012","journal-title":"Pharm. Dev. Technol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1517\/17425247.5.6.615","article-title":"Analysis of initial burst in PLGA microparticles","volume":"5","author":"Allison","year":"2008","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"128ra39","DOI":"10.1126\/scitranslmed.3003651","article-title":"Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile","volume":"4","author":"Hrkach","year":"2012","journal-title":"Sci. Transl. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/1\/273\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:47:06Z","timestamp":1760190426000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/1\/273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,31]]},"references-count":144,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["ijms21010273"],"URL":"https:\/\/doi.org\/10.3390\/ijms21010273","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,31]]}}}