Ultrasound protein-copolymer microbubble library engineering through poly(vinylpyrrolidone-co-acrylic acid) structure.

Autor: Estifeeva TM; Center for Photonic Science and Engineering, Skolkovo Institute of Science and Technology, Moscow 121205, Russia., Nechaeva AM; Department of Biomaterials, Dmitry Mendeleev University of Chemical Technology of Russia, Moscow 125047, Russia., Le-Deygen IM; Chemical Enzymology Department, Lomonosov Moscow State University, Moscow 119991, Russia., Adelyanov AM; Physics Department, Lomonosov Moscow State University, Moscow 119991, Russia., Grigoryan IV; Physics Department, Lomonosov Moscow State University, Moscow 119991, Russia., Petrovskii VS; Physics Department, Lomonosov Moscow State University, Moscow 119991, Russia., Potemkin II; Physics Department, Lomonosov Moscow State University, Moscow 119991, Russia., Abramov AA; Laboratory of Experimental Heart Pathology, Institute of Experimental Cardiology, Chazov National Medical Research Center for Cardiology, Ministry of Health of Russia, Moscow 121552, Russia., Prosvirnin AV; Laboratory of Experimental Heart Pathology, Institute of Experimental Cardiology, Chazov National Medical Research Center for Cardiology, Ministry of Health of Russia, Moscow 121552, Russia., Sencha EA; Department of Clinical Ultrasound and Functional Diagnostics, M.F. Vladimirsky Moscow Regional Clinical Research Institute (MONIKI), Moscow 129110, Russia., Borozdenko DA; Department of Medicinal Chemistry and Toxicology, Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow 117997, Russia., Barmin RA; Center for Photonic Science and Engineering, Skolkovo Institute of Science and Technology, Moscow 121205, Russia. Electronic address: roman.barmin@skoltech.ru., Mezhuev YO; Department of Biomaterials, Dmitry Mendeleev University of Chemical Technology of Russia, Moscow 125047, Russia; A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Moscow 119334, Russia., Gorin DA; Center for Photonic Science and Engineering, Skolkovo Institute of Science and Technology, Moscow 121205, Russia., Rudakovskaya PG; Center for Photonic Science and Engineering, Skolkovo Institute of Science and Technology, Moscow 121205, Russia. Electronic address: p.rudakovskaya@skoltech.ru.
Jazyk: angličtina
Zdroj: Biomaterials advances [Biomater Adv] 2025 Jan; Vol. 166, pp. 214074. Date of Electronic Publication: 2024 Oct 21.
DOI: 10.1016/j.bioadv.2024.214074
Abstrakt: Hypothesis: While albumin-coated microbubbles are routine contrast agents for ultrasound imaging, their short duration of contrast enhancement limits their use, yet can be improved by incorporating protein-copolymer hybrids into microbubble shells. The incorporation of N-vinyl-2-pyrrolidone and acrylic acid copolymer (P(VP-AA)) has been shown to enhance the performance of bovine serum albumin (BSA)-coated microbubbles. However, the impact of the copolymer structural properties on key microbubble characteristics (i.e., concentration, mean diameter and acoustic response) remains poorly understood. Therefore, we hypothesize that the copolymer structure affects its capacity to form micelle-like nanoaggregates, protein-copolymer hybrids, and microbubble shells, ultimately influencing the physicochemical and acoustic properties of the microbubbles.
Experiments: Here we evaluate the production and performance of BSA@P(VP-AA) microbubbles synthesized using a series of P(VP-AA) copolymers with -C 8 H 17 and -C 18 H 37 end groups and molecular weight cutoffs between 3.5 and 15 kDa. Both simulation and experimental data demonstrate that interactions between BSA and the copolymers significantly influence the performance of the resulting microbubbles across the library of 60 formulations.
Findings: The introduction of -C 8 H 17 terminated copolymers into microbubble shells resulted in up to 200-fold higher concentration, 7-fold greater acoustic response, and 5-fold longer ultrasound contrast enhancement compared to plain BSA microbubbles. The enhanced acoustic performance was sustained during in vivo cardiac ultrasound imaging, without altering liver accumulation after copolymer introduction. These findings underscore how optimizing copolymer structure (specifically the terminal end group and molecular weight) can tailor the formation and performance of protein-copolymer-coated microbubbles, offering valuable insights for designing ultrasound contrast agents.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: