{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:46:33Z","timestamp":1788443193334,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["NCN\/2016\/21\/B\/ST5\/01365"],"award-info":[{"award-number":["NCN\/2016\/21\/B\/ST5\/01365"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["POPW.01.03.00-20-034\/09-00"],"award-info":[{"award-number":["POPW.01.03.00-20-034\/09-00"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["POPW.01.03.00-20-004\/11"],"award-info":[{"award-number":["POPW.01.03.00-20-004\/11"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["SUB\/3\/DN\/21\/001\/3327"],"award-info":[{"award-number":["SUB\/3\/DN\/21\/001\/3327"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU","award":["NCN\/2016\/21\/B\/ST5\/01365"],"award-info":[{"award-number":["NCN\/2016\/21\/B\/ST5\/01365"]}]},{"name":"EU","award":["POPW.01.03.00-20-034\/09-00"],"award-info":[{"award-number":["POPW.01.03.00-20-034\/09-00"]}]},{"name":"EU","award":["POPW.01.03.00-20-004\/11"],"award-info":[{"award-number":["POPW.01.03.00-20-004\/11"]}]},{"name":"EU","award":["SUB\/3\/DN\/21\/001\/3327"],"award-info":[{"award-number":["SUB\/3\/DN\/21\/001\/3327"]}]},{"name":"Medical University of Bialystok","award":["NCN\/2016\/21\/B\/ST5\/01365"],"award-info":[{"award-number":["NCN\/2016\/21\/B\/ST5\/01365"]}]},{"name":"Medical University of Bialystok","award":["POPW.01.03.00-20-034\/09-00"],"award-info":[{"award-number":["POPW.01.03.00-20-034\/09-00"]}]},{"name":"Medical University of Bialystok","award":["POPW.01.03.00-20-004\/11"],"award-info":[{"award-number":["POPW.01.03.00-20-004\/11"]}]},{"name":"Medical University of Bialystok","award":["SUB\/3\/DN\/21\/001\/3327"],"award-info":[{"award-number":["SUB\/3\/DN\/21\/001\/3327"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer is the fourth most common cancer worldwide and the third most frequently diagnosed form of cancer associated with high mortality rates. Recently, targeted drug delivery systems have been under increasing attention owing to advantages such as high therapeutic effectiveness with a significant depletion in adverse events. In this report, we describe the biocompatible and thermoresponsive FA-conjugated PHEA-b-PNIPAAm copolymers as nanocarriers for the delivery of 5-FU. The block copolymers were obtained using RAFT (Reversible Addition\u2013Fragmentation chain Transfer) polymerization and were characterized by methods such as SEC (Size Exclusion Chromatography), NMR (Nuclear Magnetic Resonance), UV\u2013Vis (Ultraviolet\u2013Visible), FT-IR (Fourier Transform Infrared) spectroscopy, and TGA (Thermogravimetric Analysis). Nanoparticles were formed from polymers with and without the drug-5-fluorouracil, which was confirmed using DLS (Dynamic Light Scattering), zeta potential measurements, and TEM (Transmission Electron Microscopy) imaging. The cloud points of the polymers were found to be close to the temperature of the human body. Eventually, polymeric carriers were tested as drug delivery systems for the safety, compatibility, and targeting of colorectal cancer cells (CRC). The biological evaluation indicated high compatibility with the representative host cells. Furthermore, it showed that proposed nanosystems might have therapeutic potential as mitigators for 5-FU-induced monocytopenia, cardiotoxicity, and other chemotherapy-associated disorders. Moreover, results show increased cytotoxicity against cancer cells compared to the drug, including a line with a drug resistance phenotype. Additionally, the ability of synthesized carriers to induce apoptosis and necrosis in treated CRC cells has been confirmed. Undoubtedly, the presented aspects of colorectal cancer therapy promise future solutions to overcome the conventional limitations of current treatment regimens for this type of cancer and to improve the quality of life of the patients.<\/jats:p>","DOI":"10.3390\/ijms24021364","type":"journal-article","created":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T02:06:03Z","timestamp":1673402763000},"page":"1364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Folic-Acid-Conjugated Thermoresponsive Polymeric Particles for Targeted Delivery of 5-Fluorouracil to CRC Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-8132","authenticated-orcid":false,"given":"Sylwia","family":"Milewska","sequence":"first","affiliation":[{"name":"Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15-361 Bialystok, Poland"},{"name":"Doctoral School, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Siemiaszko","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15-245 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8587-6711","authenticated-orcid":false,"given":"Agnieszka Zofia","family":"Wilczewska","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15-245 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6191-6053","authenticated-orcid":false,"given":"Iwona","family":"Misztalewska-Turkowicz","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15-245 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4857-0489","authenticated-orcid":false,"given":"Karolina Halina","family":"Markiewicz","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15-245 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8225-3196","authenticated-orcid":false,"given":"Dawid","family":"Szymczuk","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15-245 Bialystok, Poland"},{"name":"Doctoral School of Exact and Natural Science, University of Bialystok, Ciolkowskiego 1K, 15-245 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6804-3459","authenticated-orcid":false,"given":"Diana","family":"Sawicka","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15-361 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halina","family":"Car","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15-361 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryszard","family":"Lazny","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15-245 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3311-7147","authenticated-orcid":false,"given":"Katarzyna","family":"Niemirowicz-Laskowska","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15-361 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"ref_1","first-page":"89","article-title":"Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors","volume":"14","author":"Rawla","year":"2019","journal-title":"Przeglad Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10732748211056692","DOI":"10.1177\/10732748211056692","article-title":"Title: Risk Factors for the Diagnosis of Colorectal Cancer","volume":"29","author":"Lewandowska","year":"2022","journal-title":"Cancer Control."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20503121211034366","DOI":"10.1177\/20503121211034366","article-title":"New approaches and procedures for cancer treatment: Current perspectives","volume":"9","author":"Debela","year":"2021","journal-title":"SAGE Open Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Francipane, M.G., Bulanin, D., and Lagasse, E. (2019). Establishment and Characterization of 5-Fluorouracil-Resistant Human Colorectal Cancer Stem-Like Cells: Tumor Dynamics under Selection Pressure. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081817"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1111\/cas.14532","article-title":"5-Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes","volume":"111","author":"Blondy","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jcrpr.2017.02.002","article-title":"Nano Drug Delivery Strategy of 5-Fluorouracil for the Treatment of Colorectal Cancer","volume":"4","author":"Chandran","year":"2017","journal-title":"J. Cancer Res. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.2147\/IJN.S257700","article-title":"Recent Advances in Designing 5-Fluorouracil Delivery Systems: A Stepping Stone in the Safe Treatment of Colorectal Cancer","volume":"15","author":"Tayebi","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev-chembioeng-073009-100847","article-title":"Polymers for drug delivery systems","volume":"1","author":"Liechty","year":"2010","journal-title":"Annu. Rev. Chem. Biomol. Eng."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/17425247.2020.1822321","article-title":"Surface-modified polymeric nanoparticles for drug delivery to cancer cells","volume":"18","author":"Ahmed","year":"2021","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3109\/02652048.2011.569763","article-title":"The manufacturing techniques of drug-loaded polymeric nanoparticles from preformed polymers","volume":"28","author":"Grabnar","year":"2011","journal-title":"J. Microencapsul."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Subhan, M.A., Yalamarty, S.S.K., Filipczak, N., Parveen, F., and Torchilin, V.P. (2021). Recent Advances in Tumor Targeting via EPR Effect for Cancer Treatment. J. Pers. Med., 11.","DOI":"10.3390\/jpm11060571"},{"key":"ref_12","first-page":"6387","article-title":"A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs","volume":"46","author":"Matsumura","year":"1986","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/s41551-021-00698-w","article-title":"The evolution of commercial drug delivery technologies","volume":"5","author":"Vargason","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2000285","DOI":"10.1002\/adtp.202000285","article-title":"Highway to Success\u2014Developing Advanced Polymer Therapeutics","volume":"4","author":"Ashford","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1142\/S2339547818300020","article-title":"The growing role of precision and personalized medicine for cancer treatment","volume":"6","author":"Krzyszczyk","year":"2018","journal-title":"Technology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1039\/C7SC04004K","article-title":"Advances in targeting the folate receptor in the treatment\/imaging of cancers","volume":"9","author":"Javaid","year":"2018","journal-title":"Chem. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Jurczyk, M., Jelonek, K., Musia\u0142-Kulik, M., Beberok, A., Wrze\u015bniok, D., and Kasperczyk, J. (2021). Single- versus Dual-Targeted Nanoparticles with Folic Acid and Biotin for Anticancer Drug Delivery. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13030326"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12645-021-00104-9","article-title":"Synergistic effect of folate-conjugated polymers and 5-fluorouracil in the treatment of colon cancer","volume":"12","author":"Siemiaszko","year":"2021","journal-title":"Cancer Nanotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.addr.2018.10.005","article-title":"Thermoresponsive polymer nanocarriers for biomedical applications","volume":"138","author":"Bordat","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1039\/C9TB02052G","article-title":"Thermoresponsive polymers and their biomedical application in tissue engineering\u2014A review","volume":"8","author":"Doberenz","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lanzalaco, S., and Armelin, E. (2017). Poly(N-isopropylacrylamide) and Copolymers: A Review on Recent Progresses in Biomedical Applications. Gels, 3.","DOI":"10.3390\/gels3040036"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7263","DOI":"10.2147\/IJN.S262582","article-title":"Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells","volume":"15","author":"Misiak","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1063\/1.3589615","article-title":"PHEA-PLLA: A New Polymer Blend for Tissue Engineering Applications","volume":"1353","author":"Pavia","year":"2011","journal-title":"AIP Conf. Proc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12063","DOI":"10.1021\/acsami.6b03820","article-title":"Tailor-Made Temperature-Sensitive Micelle for Targeted and On-Demand Release of Anticancer Drugs","volume":"8","author":"Panja","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.biomaterials.2006.11.013","article-title":"Bio-functional micelles self-assembled from a folate-conjugated block copolymer for targeted intracellular delivery of anticancer drugs","volume":"28","author":"Liu","year":"2007","journal-title":"Biomaterials"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ijpharm.2012.07.069","article-title":"Folate-decorated thermoresponsive micelles based on star-shaped amphiphilic block copolymers for efficient intracellular release of anticancer drugs","volume":"437","author":"Rezaei","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.carbpol.2017.05.007","article-title":"Folate-conjugated thermosensitive O-maleoyl modified chitosan micellar nanoparticles for targeted delivery of erlotinib","volume":"172","author":"Fathi","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8268","DOI":"10.1039\/C5TB01063B","article-title":"Folic acid-tethered poly(N-isopropylacrylamide)-phospholipid hybrid nanocarriers for targeted drug delivery","volume":"3","author":"John","year":"2015","journal-title":"J. Mater. Chem. B"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1021\/bm701255v","article-title":"Folate-conjugated thermoresponsive block copolymers: Highly efficient conjugation and solution self-assembly","volume":"9","author":"De","year":"2008","journal-title":"Biomacromolecules"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1039\/C7PY00161D","article-title":"\u201cClick\u201d Functionalization of Dual Stimuli-Responsive Polymer Nanocapsules for Drug Delivery Systems","volume":"8","author":"Yang","year":"2017","journal-title":"Polym. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jcis.2014.05.008","article-title":"Folic acid-conjugated pH\/temperature\/redox multi-stimuli responsive polymer microspheres for delivery of anti-cancer drug","volume":"429","author":"Li","year":"2014","journal-title":"J. Colloid Interface Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"41090","DOI":"10.1038\/srep41090","article-title":"Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles","volume":"7","author":"Kim","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.colsurfb.2010.08.037","article-title":"Evaluation of folate conjugated pegylated thermosensitive magnetic nanocomposites for tumor imaging and therapy","volume":"82","author":"Rastogi","year":"2011","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"29653","DOI":"10.1039\/C5RA01444A","article-title":"Multilayer Fluorescent Magnetic Nanoparticles with Dual Thermoresponsive and PH-Sensitive Polymeric Nanolayers as Anti-Cancer Drug Carriers","volume":"5","year":"2015","journal-title":"RSC Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1166\/asem.2014.1508","article-title":"Folic Acid Conjugated-Bio Polymeric Nanocarriers: Synthesis, Characterization and In Vitro Delivery of Prodrug Converting Enzyme","volume":"6","author":"Yata","year":"2014","journal-title":"Adv. Sci. Eng. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1021\/bc010084g","article-title":"Preparation and tumor cell uptake of poly(N-isopropylacrylamide) folate conjugates","volume":"13","author":"Francis","year":"2002","journal-title":"Bioconjugate Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s11671-020-03444-4","article-title":"Near-Infrared Light-Triggered Thermo-responsive Poly(N-Isopropylacrylamide)-Pyrrole Nanocomposites for Chemo-photothermal Cancer Therapy","volume":"15","author":"Shin","year":"2020","journal-title":"Nanoscale Res. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/BF00468341","article-title":"Some characteristic properties of 3-alkyl-2-thiothiazon-4-ones and of intermediates in their synthesis","volume":"3","author":"Turkevich","year":"1967","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1002\/pola.24612","article-title":"Chain transfer to solvent in the radical polymerization of N-isopropylacrylamide","volume":"49","author":"Sugihara","year":"2011","journal-title":"J. Polym. Sci. Part A Polym. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/0969-806X(95)00277-5","article-title":"Radiation preparation of the water-soluble, temperature sensitive polymers in organic solvents","volume":"46","author":"Yi","year":"1995","journal-title":"Radiat. Phys. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1021\/bm501558d","article-title":"In vivo evaluation of folate decorated cross-linked micelles for the delivery of platinum anticancer drugs","volume":"16","author":"Eliezar","year":"2015","journal-title":"Biomacromolecules"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7388","DOI":"10.1002\/chem.201800283","article-title":"A Magnetic Chameleon: Biocompatible Lanthanide Fluoride Nanoparticles with Magnetic Field Dependent Tunable Contrast Properties as a Versatile Contrast Agent for Low to Ultrahigh Field MRI and Optical Imaging in Biological Window","volume":"24","author":"Biju","year":"2018","journal-title":"Chemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jphotobiol.2005.03.001","article-title":"Ultraviolet photodegradation of folic acid","volume":"80","author":"Off","year":"2005","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/0079-6700(92)90023-R","article-title":"Poly(N-Isopropylacrylamide): Experiment, Theory and Application","volume":"17","author":"Schild","year":"1992","journal-title":"Prog. Polym. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/B978-0-444-64199-1.00004-X","article-title":"Chemopreventive Role of Dietary Phytochemicals in Colorectal Cancer","volume":"12","author":"Bansal","year":"2018","journal-title":"Adv. Mol. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.2147\/IJN.S132780","article-title":"High drug-loading nanomedicines: Progress, current status, and prospects","volume":"12","author":"Shen","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.2174\/0929867324666170111152436","article-title":"Colorectal Cancer Chemotherapy: The Evolution of Treatment and New Approaches","volume":"24","author":"McQuade","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"107447","DOI":"10.1016\/j.pharmthera.2019.107447","article-title":"5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future","volume":"206","author":"Vodenkova","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1080\/10717544.2019.1582729","article-title":"Poly(3-hydroxybutyrate-CO-3-hydroxyvalerate) PHBHV biocompatible nanocarriers for 5-FU delivery targeting colorectal cancer","volume":"26","author":"Radu","year":"2019","journal-title":"Drug Deliv."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"de la Harpe, K.M., Kondiah, P.P.D., Choonara, Y.E., Marimuthu, T., du Toit, L.C., and Pillay, V. (2019). The Hemocompatibility of Nanoparticles: A Review of Cell-Nanoparticle Interactions and Hemostasis. Cells, 8.","DOI":"10.3390\/cells8101209"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"21300073","DOI":"10.1142\/S1793292021300073","article-title":"Hemocompatibility and Hemolytic Effects of Functionalized Nanoparticles on Red Blood Cells: A Recent Review Study","volume":"16","author":"Mehrizi","year":"2021","journal-title":"Nano"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1002\/jps.20627","article-title":"In vitro hemolysis: Guidance for the pharmaceutical scientist","volume":"95","author":"Amin","year":"2006","journal-title":"J. Pharm. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fbioe.2018.00099","article-title":"Blood-Contacting Biomaterials: In Vitro Evaluation of the Hemocompatibility","volume":"6","author":"Weber","year":"2018","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0162-3109(90)90048-J","article-title":"Resistance of macrophages to 5-fluorouracil treatment","volume":"19","author":"Bilej","year":"1990","journal-title":"Immunopharmacology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"438","DOI":"10.21037\/atm.2016.08.53","article-title":"THP-1 cells as a model for human monocytes","volume":"4","author":"Bosshart","year":"2016","journal-title":"Ann. Transl. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/00000421-199902000-00025","article-title":"Early monocytopenia after chemotherapy as a risk factor for neutropenia","volume":"22","author":"Kondo","year":"1999","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1080\/02841860151116204","article-title":"What is cancer chemotherapy?","volume":"40","author":"Nygren","year":"2001","journal-title":"Acta Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1080\/02841860151116367","article-title":"A systematic overview of chemotherapy effects in colorectal cancer","volume":"40","author":"Ragnhammar","year":"2001","journal-title":"Acta Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1758835918780140","DOI":"10.1177\/1758835918780140","article-title":"5-fluorouracil and cardiotoxicity: A review","volume":"10","author":"Sara","year":"2018","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/0014-4835(91)90116-V","article-title":"Effects of 5-fluorouracil on proliferating fibroblasts in vivo","volume":"53","author":"Ophir","year":"1991","journal-title":"Exp. Eye Res."},{"key":"ref_61","first-page":"4593","article-title":"Preparation and in vitro studies of MRI-specific superparamagnetic iron oxide antiGPC3 probe for hepatocellular carcinoma","volume":"7","author":"Li","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"111285","DOI":"10.1016\/j.biopha.2021.111285","article-title":"5-Fluorouracil (5-FU) resistance and the new strategy to enhance the sensitivity against cancer: Implication of DNA repair inhibition","volume":"137","author":"Sethy","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1093\/jn\/131.11.2819","article-title":"Folate receptor function is regulated in response to different cellular growth rates in cultured mammalian cells","volume":"131","author":"Doucette","year":"2001","journal-title":"J. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.carres.2011.01.027","article-title":"Synthesis and characterization of folate conjugated chitosan and cellular uptake of its nanoparticles in HT-29 cells","volume":"346","author":"Li","year":"2011","journal-title":"Carbohydr. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/sj.bjc.6605780","article-title":"5-Fluorouracil response in a large panel of colorectal cancer cell lines is associated with mismatch repair deficiency","volume":"103","author":"Bracht","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Moodley, T., and Singh, M. (2019). Polymeric Mesoporous Silica Nanoparticles for Enhanced Delivery of 5-Fluorouracil In Vitro. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11060288"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"635","DOI":"10.3109\/10837450.2015.1116565","article-title":"Preparation and in vitro evaluation of 5-fluorouracil-loaded PCL nanoparticles for colon cancer treatment","volume":"22","author":"Mashal","year":"2017","journal-title":"Pharm. Dev. Technol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3109\/10717544.2013.875603","article-title":"Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles","volume":"22","author":"Wang","year":"2015","journal-title":"Drug Deliv."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.actbio.2015.10.010","article-title":"Fluorescence imaging enabled poly(lactide-co-glycolide)","volume":"29","author":"Hu","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1071\/CH13425","article-title":"Azobenzene-Functionalised Core Cross-Linked Star Polymers and their Host\u2013Guest Interactions","volume":"67","author":"Tan","year":"2013","journal-title":"Aust. J. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1039\/C6PY00499G","article-title":"Low concentration thermoresponsive hydrogels from readily accessible triblock copolymers","volume":"7","author":"Despax","year":"2016","journal-title":"Polym. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1364\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:06:00Z","timestamp":1760119560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,10]]},"references-count":71,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24021364"],"URL":"https:\/\/doi.org\/10.3390\/ijms24021364","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,10]]}}}