{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:43:22Z","timestamp":1785548602442,"version":"3.56.0"},"reference-count":44,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Lombardia","award":["POR FESR 2014\u20132020"],"award-info":[{"award-number":["POR FESR 2014\u20132020"]}]},{"name":"Regione Lombardia","award":["1175999"],"award-info":[{"award-number":["1175999"]}]},{"name":"NEWMED project","award":["POR FESR 2014\u20132020"],"award-info":[{"award-number":["POR FESR 2014\u20132020"]}]},{"name":"NEWMED project","award":["1175999"],"award-info":[{"award-number":["1175999"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A thermoresponsive copolymer based on oligo(ethylene glycol) methacrylate, Chol-P(MEO2MA-co-OEGMA), was synthesized using Atom Transfer Radical Polymerization (ATRP) and incorporated into thermosensitive liposomes (TSLs) for controlled drug release. The copolymer exhibited a lower critical solution temperature (LCST) of 37 \u00b0C, making it suitable for biomedical applications requiring precise thermal triggers. The copolymer was incorporated into various TSL formulations alongside phospholipids such as DPPC, Lyso-PC, HSPC, and DSPC. Physicochemical characterization of the liposomes, including average size, polydispersity index, loading efficiency (LE), and encapsulation efficiency (EE), was performed using dynamic light scattering and fluorescence spectroscopy. The results showed that the incorporation of the copolymer slightly affected particle size and decreased LE and EE in most formulations. Lyso-PC-containing formulations exhibited lower LE and EE, likely due to instability during purification. Albumin encapsulation demonstrated lower LE compared to the smaller carboxyfluorescein drug model, highlighting the influence of molecular weight on loading. Although copolymer-modified liposomes showed reduced loading capacity, they enhanced thermoresponsiveness in HSPC-based formulations. These findings suggest that incorporating thermoresponsive polymers into TSLs can optimize drug delivery systems for targeted, thermally triggered release.<\/jats:p>","DOI":"10.3390\/molecules29235511","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T12:24:51Z","timestamp":1732191891000},"page":"5511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Oligo(ethylene glycol) Methacrylate Copolymer-Modified Liposomes for Temperature-Responsive Drug Delivery System"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3823-1069","authenticated-orcid":false,"given":"Maria Isabel","family":"Martinez Espinoza","sequence":"first","affiliation":[{"name":"Department of Chemistry, Materials and Chemical Engineering \u201cG. Natta\u201d, Politecnico di Milano, Via Mancinelli 7, 20131 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sezen","family":"G\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Materials and Chemical Engineering \u201cG. Natta\u201d, Politecnico di Milano, Via Mancinelli 7, 20131 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Mugnaini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Materials and Chemical Engineering \u201cG. Natta\u201d, Politecnico di Milano, Via Mancinelli 7, 20131 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6106-9317","authenticated-orcid":false,"given":"Francesco","family":"Cellesi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Materials and Chemical Engineering \u201cG. Natta\u201d, Politecnico di Milano, Via Mancinelli 7, 20131 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.addr.2012.09.037","article-title":"Liposomal drug delivery systems: From concept to clinical applications","volume":"65","author":"Allen","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113851","DOI":"10.1016\/j.addr.2021.113851","article-title":"Liposome composition in drug delivery design, synthesis, characterization, and clinical application","volume":"176","author":"Large","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"907","DOI":"10.3390\/molecules23040907","article-title":"Liposomal Drug Delivery Systems and Anticancer Drugs","volume":"23","author":"Olusanya","year":"2018","journal-title":"Molecules"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s11671-021-03553-8","article-title":"Liposomal Nanomedicine: Applications for Drug Delivery in Cancer Therapy","volume":"16","author":"Rommasi","year":"2021","journal-title":"Nanoscale Res. Lett."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Liu, P., Chen, G.L., and Zhang, J.C. (2022). A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives. Molecules, 27.","DOI":"10.3390\/molecules27041372"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e09394","DOI":"10.1016\/j.heliyon.2022.e09394","article-title":"Liposomes: Structure, composition, types, and clinical applications","volume":"8","author":"Nsairat","year":"2022","journal-title":"Heliyon"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ijpharm.2005.04.029","article-title":"Encapsulation efficiency of water-soluble and insoluble drugs in liposomes prepared by the microencapsulation vesicle method","volume":"298","author":"Nii","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ijpharm.2017.03.090","article-title":"The effect of thermosensitive liposomal formulations on loading and release of high molecular weight biomolecules","volume":"524","author":"Huang","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"124322","DOI":"10.1016\/j.ijpharm.2024.124322","article-title":"Brain-Derived Neurotrophic Factor-Loaded Low-Temperature-Sensitive liposomes as a drug delivery system for repairing podocyte damage","volume":"660","author":"Huang","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3109\/08982104.2012.655285","article-title":"Factors affecting the pharmacokinetics and pharmacodynamics of liposomal drugs","volume":"22","author":"Song","year":"2012","journal-title":"J. Liposome Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"114895","DOI":"10.1016\/j.addr.2023.114895","article-title":"Stealth and pseudo-stealth nanocarriers","volume":"198","author":"Wen","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, S., Chen, Y., Guo, J., and Huang, Q. (2023). Liposomes for Tumor Targeted Therapy: A Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032643"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3715","DOI":"10.7150\/thno.19678","article-title":"Selective Targeting of a Novel Vasodilator to the Uterine Vasculature to Treat Impaired Uteroplacental Perfusion in Pregnancy","volume":"7","author":"Cureton","year":"2017","journal-title":"Theranostics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e1600349","DOI":"10.1126\/sciadv.1600349","article-title":"Tumor-homing peptides as tools for targeted delivery of payloads to the placenta","volume":"2","author":"King","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_15","first-page":"276","article-title":"Liposomes for Drug Delivery","volume":"2017","author":"Yadav","year":"2017","journal-title":"J. Biotechnol. Biomater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1556-276X-8-102","article-title":"Liposome: Classification, preparation, and applications","volume":"8","author":"Akbarzadeh","year":"2013","journal-title":"Nanoscale Res. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mazzotta, E., Tavano, L., and Muzzalupo, R. (2018). Thermo-Sensitive Vesicles in Controlled Drug Delivery for Chemotherapy. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030150"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1080\/17425247.2022.2099834","article-title":"Thermosensitive liposomes: A promising step toward localised chemotherapy","volume":"19","author":"Chaudhry","year":"2022","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kuijten, M.M.P., Hannah Degeling, M., Chen, J.W., Wojtkiewicz, G., Waterman, P., Weissleder, R., Azzi, J., Nicolay, K., and Tannous, B.A. (2015). Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging. Sci. Rep., 5.","DOI":"10.1038\/srep17220"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jconrel.2017.01.025","article-title":"To heat or not to heat: Challenges with clinical translation of thermosensitive liposomes","volume":"249","author":"Dou","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0169-409X(01)00204-6","article-title":"Thermosensitive polymer-modified liposomes","volume":"53","author":"Kono","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.colsurfb.2017.01.002","article-title":"Stability effect of cholesterol-poly(acrylic acid) in a stimuli-responsive polymer-liposome complex obtained from soybean lecithin for controlled drug delivery","volume":"152","author":"Alves","year":"2017","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1021\/acsbiomaterials.9b00343","article-title":"Quick-Responsive Polymer-Based Thermosensitive Liposomes for Controlled Doxorubicin Release and Chemotherapy","volume":"5","author":"Mo","year":"2019","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1021\/ma0517042","article-title":"Preparation of Ideal PEG Analogues with a Tunable Thermosensitivity by Controlled Radical Copolymerization of 2-(2-Methoxyethoxy)ethyl Methacrylate and Oligo(ethylene glycol) Methacrylate","volume":"39","author":"Lutz","year":"2006","journal-title":"Macromolecules"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/s41565-024-01754-7","article-title":"A translational framework to DELIVER nanomedicines to the clinic","volume":"19","author":"Joyce","year":"2024","journal-title":"Nat. Nanotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"110226","DOI":"10.1016\/j.eurpolymj.2020.110226","article-title":"Complex poly(\u03b5-caprolactone)\/poly(ethylene glycol) copolymer architectures and their effects on nanoparticle self-assembly and drug nanoencapsulation","volume":"144","author":"Celentano","year":"2021","journal-title":"Eur. Polym. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"113455","DOI":"10.1016\/j.eurpolymj.2024.113455","article-title":"Tailoring copolymer architectures and macromolecular interactions for enhanced nanotherapeutic delivery: A design-by-architecture approach","volume":"220","author":"Porello","year":"2024","journal-title":"Eur. Polym. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.progpolymsci.2019.01.001","article-title":"Rational design of thermoresponsive polymers in aqueous solutions: A thermodynamics map","volume":"90","author":"Zhao","year":"2019","journal-title":"Prog. Polym. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Abraham, T., Mao, M., and Tan, C. (2018). Engineering approaches of smart, bio-inspired vesicles for biomedical applications. Phys. Biol., 15.","DOI":"10.1088\/1478-3975\/aac7a2"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ajps.2014.09.004","article-title":"A review on phospholipids and their main applications in drug delivery systems","volume":"10","author":"Li","year":"2015","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3883","DOI":"10.1021\/acs.chemrev.5b00578","article-title":"Chemical Components for the Design of Temperature-Responsive Vesicles as Cancer Therapeutics","volume":"116","author":"Kostarelos","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1016\/j.bbamem.2007.05.021","article-title":"In vitro stability and content release properties of phosphatidylglyceroglycerol containing thermosensitive liposomes","volume":"1768","author":"Hossann","year":"2007","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"491","DOI":"10.3109\/08982109909035549","article-title":"Enhancement of the Phase Transition Permeability of DPPC Liposomes by Incorporation of MPPC: A New Temperature-Sensitive Liposome for use with Mild Hyperthermia","volume":"9","author":"Anyarambhatla","year":"1999","journal-title":"J. Liposome Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1039\/C2FD20111A","article-title":"Materials characterization of the low temperature sensitive liposome (LTSL): Effects of the lipid composition (lysolipid and DSPE\u2013PEG2000) on the thermal transition and release of doxorubicin","volume":"161","author":"Needham","year":"2013","journal-title":"Faraday Discuss."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jconrel.2016.12.030","article-title":"Inhomogeneous crystal grain formation in DPPC-DSPC based thermosensitive liposomes determines content release kinetics","volume":"247","author":"Lu","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.ajps.2018.07.006","article-title":"Current developments in drug delivery with thermosensitive liposomes","volume":"14","author":"Bi","year":"2019","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ijbiomac.2012.10.030","article-title":"Bovine serum albumin oligomers in the E- and B-forms at low protein concentration and ionic strength","volume":"53","author":"Babcock","year":"2013","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6866","DOI":"10.1021\/la800548p","article-title":"Characterization of Globular Protein Solutions by Dynamic Light Scattering, Electrophoretic Mobility, and Viscosity Measurements","volume":"24","author":"Jachimska","year":"2008","journal-title":"Langmuir"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bae, W., Yoon, T.Y., and Jeong, C. (2021). Direct evaluation of self-quenching behavior of fluorophores at high concentrations using an evanescent field. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247326"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ijpharm.2004.07.045","article-title":"The effects of lyophilization on the stability of liposomes containing 5-FU","volume":"291","author":"Goracinova","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ijpharm.2011.09.016","article-title":"Development of lysolipid-based thermosensitive liposomes for delivery of high molecular weight proteins","volume":"421","author":"Zhang","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0378-5173(86)90184-5","article-title":"The adsorption of bovine serum albumin by liposomes","volume":"32","author":"Law","year":"1986","journal-title":"Int. J. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0927-7765(00)00176-4","article-title":"Effect of adsorption of bovine serum albumin on liposomal membrane characteristics","volume":"20","author":"Yokouchi","year":"2001","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0076-6879(04)87005-8","article-title":"Temperature-sensitive liposomes","volume":"387","author":"Kono","year":"2004","journal-title":"Methods Enzymol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/23\/5511\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:37:07Z","timestamp":1760114227000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/23\/5511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,21]]},"references-count":44,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["molecules29235511"],"URL":"https:\/\/doi.org\/10.3390\/molecules29235511","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,21]]}}}