{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:20:08Z","timestamp":1788358808749,"version":"build-2803163510"},"reference-count":35,"publisher":"American Chemical Society (ACS)","issue":"25","license":[{"start":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:00:00Z","timestamp":1592265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1R35GM119839-01"],"award-info":[{"award-number":["1R35GM119839-01"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009612","name":"Oregon State University","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100009612","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The folate analogue pemetrexed (PEM) is an approved therapeutic for non-small cell lung cancer and malignant pleural mesothelioma with the potential for broader application in combination therapies. Here, we report the development of a nanoformulation of PEM and its efficacy against the CT26 murine colorectal cancer cell line in vitro and in vivo. Utilizing layer-by-layer deposition, we integrate PEM, along with folic acid (FA), onto a fluorescent polystyrene nanoparticle (NP) substrate. The final nanoformulation (PEM\/FA-NP) has a size of \u223c40 nm and a zeta potential of approximately \u221220 mV. Cell uptake studies indicated increased uptake in vitro for the PEM\/FA-NP compared to the uncoated NP, likely due to the presence of PEM and FA. Viability studies were performed to determine the potency of the PEM\/FA-NP formulation against CT26 cells. Syngeneic CT26 tumors in BALB\/c mice showed reduced growth when treated once daily (2.1 mg\/kg PEM) for 3 days with PEM\/FA-NP versus the vehicle (uncoated) control, with no observable signs of systemic toxicity associated with the nanoformulation. Although the current study size is limited (n = 4 animals for each group), the overall performance and biocompatibility of the PEM\/FA-NP observed suggest that further optimization and larger-scale studies may be warranted for this novel formulation.<\/jats:p>","DOI":"10.1021\/acsomega.0c01550","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T12:16:25Z","timestamp":1592309785000},"page":"15424-15432","source":"Crossref","is-referenced-by-count":10,"title":["Development of a Pemetrexed\/Folic Acid Nanoformulation:\nSynthesis, Characterization, and Efficacy in a Murine Colorectal Cancer\nModel"],"prefix":"10.1021","volume":"5","author":[{"given":"Justin G.","family":"Rosch","sequence":"first","affiliation":[{"name":"Oregon State University , , , ,","place":["Portland, Oregon, United States, 97201"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison N.","family":"DuRoss","sequence":"additional","affiliation":[{"name":"Oregon State University , , , ,","place":["Portland, Oregon, United States, 97201"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine R.","family":"Landry","sequence":"additional","affiliation":[{"name":"Oregon State University , , , ,","place":["Portland, Oregon, United States, 97201"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5193-6907","authenticated-orcid":true,"given":"Conroy","family":"Sun","sequence":"additional","affiliation":[{"name":"Oregon State University , , , ,","place":["Portland, Oregon, United States, 97201"]},{"name":"Oregon Health & Science University , , , ,","place":["Portland, Oregon, United States, 97239"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,6,16]]},"reference":[{"key":"2026090210115943600_cit1","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1016\/S1359-6446","article-title":"Nanotech Approaches\nto Drug Delivery and Imaging","volume":"8","author":"Sahoo","year":"2003","journal-title":"Drug Discovery\nToday"},{"key":"2026090210115943600_cit2","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1021\/nl200636r","article-title":"Controlling in Vivo\nStability and Biodistribution in Electrostatically Assembled Nanoparticles\nfor Systemic Delivery","volume":"11","author":"Poon","year":"2011","journal-title":"Nano Lett."},{"key":"2026090210115943600_cit3","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1023\/B:PHAM.0000016249.52831.a5","article-title":"Uptake and Cytotoxicity of Chitosan\nMolecules and Nanoparticles: Effects of Molecular Weight and Degree\nof Deacetylation","volume":"21","author":"Huang","year":"2004","journal-title":"Pharm. Res."},{"key":"2026090210115943600_cit4","doi-asserted-by":"publisher","first-page":"110824","DOI":"10.1016\/j.colsurfb.2020.110824","article-title":"Synthesis\nof Lactoferrin Mesoporous\nSilica Nanoparticles for Pemetrexed\/Ellagic Acid Synergistic Breast\nCancer Therapy","volume":"188","author":"Ali","year":"2020","journal-title":"Colloids Surf., B"},{"key":"2026090210115943600_cit5","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.pharmthera.2013.11.007","article-title":"Integration\nof Molecular Targeted\nTherapy with Radiation in Head and Neck Cancer","volume":"142","author":"Du","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"2026090210115943600_cit6","doi-asserted-by":"publisher","first-page":"e447","DOI":"10.1016\/j.ijrobp.2012.05.019","article-title":"The Clinical Development\nof Molecularly Targeted Agents\nin Combination With Radiation Therapy: A Pharmaceutical Perspective","volume":"84","author":"Ataman","year":"2012","journal-title":"Int. J. Radiat. Oncol., Biol., Phys."},{"key":"2026090210115943600_cit7","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/nrclinonc.2016.79","article-title":"Clinical Development\nof New Drug\u2013Radiotherapy Combinations","volume":"13","author":"Sharma","year":"2016","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"2026090210115943600_cit8","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.ijpharm.2018.09.019","article-title":"Theranostic Polymeric Nanoparticles\nfor NIR Imaging and Photodynamic Therapy","author":"Sarcan","year":"2018","journal-title":"Int.\nJ. Pharm."},{"key":"2026090210115943600_cit9","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.1007\/s00432-016-2179-3","article-title":"Folate-Conjugated\nGold Nanoparticle as a New Nanoplatform for Targeted Cancer Therapy","volume":"142","author":"Samadian","year":"2016","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"2026090210115943600_cit10","doi-asserted-by":"publisher","first-page":"4049","DOI":"10.1021\/acs.molpharmaceut.8b00473","article-title":"Hyaluronic Acid-Methotrexate Conjugates\nCoated Magnetic Polydopamine Nanoparticles for Multimodal Imaging-Guided\nMultistage Targeted Chemo-Photothermal Therapy","volume":"15","author":"Li","year":"2018","journal-title":"Mol. Pharmaceutics"},{"key":"2026090210115943600_cit11","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/B978-012369448-5.50012-4","article-title":"Targeting Thymidylate Synthase\nby Antifolate Drugs for the Treatment of Cancer","volume-title":"Cancer Drug Design and Discovery","author":"Jackman","year":"2008"},{"key":"2026090210115943600_cit12","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/j.addr.2004.01.003","article-title":"Antifolates Targeted Specifically\nto the Folate Receptor","volume":"56","author":"Jackman","year":"2004","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026090210115943600_cit13","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1021\/acsomega.7b01437","article-title":"Simultaneous\nBinding of Folic Acid\nand Methotrexate to Human Serum Albumin: Insights into the Structural\nChanges of Protein and the Location and Competitive Displacement of\nDrugs","volume":"3","author":"Panja","year":"2018","journal-title":"ACS Omega"},{"key":"2026090210115943600_cit14","doi-asserted-by":"publisher","first-page":"6349","DOI":"10.1021\/acsomega.7b01105","article-title":"Folate-PEG\nConjugates\nof a Far-Red Light-Activatable Paclitaxel Prodrug to Improve Selectivity\ntoward Folate Receptor-Positive Cancer Cells","volume":"2","author":"Thapa","year":"2017","journal-title":"ACS Omega"},{"key":"2026090210115943600_cit15","doi-asserted-by":"publisher","first-page":"13952","DOI":"10.1021\/acsomega.8b01619","article-title":"Folic Acid-Conjugated\nCellulose Nanocrystals Show High Folate-Receptor Binding Affinity\nand Uptake by KB and Breast Cancer Cells","volume":"3","author":"Bittleman","year":"2018","journal-title":"ACS\nOmega"},{"key":"2026090210115943600_cit16","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1016\/j.biomaterials.2006.11.013","article-title":"Bio-Functional\nMicelles Self-Assembled from a Folate-Conjugated Block Copolymer for\nTargeted Intracellular Delivery of Anticancer Drugs","volume":"28","author":"Liu","year":"2007","journal-title":"Biomaterials"},{"key":"2026090210115943600_cit17","doi-asserted-by":"publisher","first-page":"11721","DOI":"10.1158\/0008-5472.CAN-05-2034","article-title":"BGC 945, a Novel Tumor-Selective Thymidylate\nSynthase Inhibitor Targeted to \u03b1-Folate Receptor-Overexpressing\nTumors","volume":"65","author":"Gibbs","year":"2005","journal-title":"Cancer Res."},{"key":"2026090210115943600_cit18","doi-asserted-by":"publisher","first-page":"5446","DOI":"10.1021\/jm400490e","article-title":"Development and Binding Mode Assessment of N-[4-[2-Propyn-1-Yl[(6S)-4,6,7,8-Tetrahydro-2-(Hydroxymethyl)-4-Oxo-3H-Cyclopenta[g]Quinazolin-6-Yl]Amino]Benzoyl]-L-\u03b3-Glutamyl-D-Glutamic\nAcid (BGC 945), a Novel Thymidylate Synthase Inhibitor That Targets\nTumor cells","volume":"56","author":"Tochowicz","year":"2013","journal-title":"J. Med. Chem."},{"key":"2026090210115943600_cit19","doi-asserted-by":"publisher","first-page":"105008","DOI":"10.1016\/j.ejps.2019.105008","article-title":"Pemetrexed-Conjugated\nHyaluronan for the Treatment of Malignant Pleural Mesothelioma","volume":"138","author":"Amano","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"2026090210115943600_cit20","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1634\/theoncologist.6-4-363","article-title":"Pemetrexed Disodium:\nA Novel Antifolate Clinically Active Against Multiple Solid Tumors","volume":"6","author":"Hanauske","year":"2001","journal-title":"Oncologist"},{"key":"2026090210115943600_cit21","doi-asserted-by":"publisher","first-page":"7175","DOI":"10.1158\/1078-0432.CCR-19-0433","article-title":"The Folate Pathway Inhibitor Pemetrexed Pleiotropically\nEnhances Effects of Cancer Immunotherapy","volume":"25","author":"Schaer","year":"2019","journal-title":"Clin.\nCancer Res."},{"key":"2026090210115943600_cit22","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1016\/S1470-2045(16)30498-3","article-title":"Carboplatin and Pemetrexed\nwith or without Pembrolizumab for Advanced, Non-Squamous Non-Small-Cell\nLung Cancer: A Randomised, Phase 2 Cohort of the Open-Label KEYNOTE-021\nStudy","volume":"17","author":"Langer","year":"2016","journal-title":"Lancet Oncol."},{"key":"2026090210115943600_cit23","doi-asserted-by":"publisher","first-page":"2566","DOI":"10.3109\/10717544.2015.1033794","article-title":"Antitumor and Antimetastatic\nEffects\nof Pemetrexed-Loaded Targeted Nanoparticles in B16 Bearing\nMice","volume":"23","author":"Lu","year":"2016","journal-title":"Drug Delivery"},{"key":"2026090210115943600_cit24","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1080\/03639045.2016.1200069","article-title":"Co-Delivery of Pemetrexed\nand MiR-21 Antisense Oligonucleotide\nby Lipid-Polymer Hybrid Nanoparticles and Effects on Glioblastoma\nCells","volume":"43","author":"Ku\u0308c\u0327u\u0308ktu\u0308rkmen","year":"2016","journal-title":"Drug Dev. Ind. Pharm."},{"key":"2026090210115943600_cit25","doi-asserted-by":"publisher","first-page":"773","DOI":"10.2147\/IJN.S186344","article-title":"Pemetrexed-Loaded Nanoparticles Targeted to Malignant Pleural Mesothelioma\nCells: An in Vitro Study","volume":"Volume 14","author":"Cova","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"2026090210115943600_cit26","doi-asserted-by":"publisher","first-page":"13947","DOI":"10.1039\/C9NR04320A","article-title":"Enhancing\nChemoradiation of Colorectal Cancer through Targeted Delivery of Raltitrexed\nby Hyaluronic Acid Coated Nanoparticles","author":"Rosch","year":"2019","journal-title":"Nanoscale"},{"key":"2026090210115943600_cit27","doi-asserted-by":"publisher","first-page":"133","DOI":"10.3390\/pharmaceutics12020133","article-title":"Formulation of Folate\n- Modified Raltitrexed- Loaded Nanoparticles for Colorectal Cancer\nTheranostics","volume":"12","author":"Rosch","year":"2020","journal-title":"Pharmaceutics"},{"key":"2026090210115943600_cit28","doi-asserted-by":"publisher","first-page":"9571","DOI":"10.1021\/nn4047925","article-title":"Layer-by-Layer Nanoparticles for Systemic Codelivery\nof an Anticancer Drug and SiRNA for Potential Triple-Negative Breast\nCancer Treatment","volume":"7","author":"Deng","year":"2013","journal-title":"ACS Nano"},{"key":"2026090210115943600_cit29","doi-asserted-by":"publisher","first-page":"7312","DOI":"10.1158\/1078-0432.CCR-16-2186","article-title":"A Combination RNAi-Chemotherapy\nLayer-by-Layer Nanoparticle for Systemic Targeting of KRAS\/P53 with\nCisplatin to Treat Non\u2013Small Cell Lung Cancer","volume":"23","author":"Gu","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"2026090210115943600_cit30","doi-asserted-by":"publisher","first-page":"5328","DOI":"10.1016\/j.biomaterials.2013.03.059","article-title":"The Architecture and Biological Performance\nof Drug-Loaded LbL Nanoparticles","volume":"34","author":"Morton","year":"2013","journal-title":"Biomaterials"},{"key":"2026090210115943600_cit31","doi-asserted-by":"publisher","first-page":"8374","DOI":"10.1021\/nn502861t","article-title":"Bimodal\nTumor-Targeting from Microenvironment\nResponsive Hyaluronan Layer-by-Layer (LbL) Nanoparticles","volume":"8","author":"Dreaden","year":"2014","journal-title":"ACS Nano"},{"key":"2026090210115943600_cit32","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1002\/adfm.201504385","article-title":"Highly Scalable,\nClosed-Loop Synthesis of Drug-Loaded,\nLayer-by-Layer Nanoparticles","volume":"26","author":"Correa","year":"2016","journal-title":"Adv. Funct. Mater."},{"key":"2026090210115943600_cit33","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.saa.2008.12.021","article-title":"Complexation\nof Anthracene with Folic Acid Studied by FTIR and UV Spectroscopies","volume":"72","author":"He","year":"2009","journal-title":"Spectrochim. Acta, Part A"},{"key":"2026090210115943600_cit34","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.bpc.2006.07.008","article-title":"FTIR Spectra of Solid Poly-l-Lysine\nin the Stretching\nNH Mode Range","volume":"125","author":"Rozenberg","year":"2007","journal-title":"Biophys. Chem."},{"key":"2026090210115943600_cit35","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.1021\/jf048083g","article-title":"Development\nof a Simplified Method for the Determination\nof Folates in Baker\u2019s Yeast by HPLC with Ultraviolet and Fluorescence\nDetection","volume":"53","author":"Patring","year":"2005","journal-title":"J. Agric. Food Chem."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.0c01550","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/25\/15424\/67785416\/acsomega.0c01550.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/25\/15424\/67785416\/acsomega.0c01550.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:12:06Z","timestamp":1788358326000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/5\/25\/15424\/975322\/Development-of-a-Pemetrexed-Folic-Acid"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,16]]},"references-count":35,"journal-issue":{"issue":"25","published-online":{"date-parts":[[2020,6,16]]},"published-print":{"date-parts":[[2020,6,30]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.0c01550","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,16]]}}}