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Thermoresponsive .beta.-glucan-based polymers for bimodal immunoradiotherapy - Are they able to promote the immune system?
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SYSNO ASEP 0480890 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Thermoresponsive .beta.-glucan-based polymers for bimodal immunoradiotherapy - Are they able to promote the immune system? Tvůrce(i) Loukotová, Lenka (UMCH-V) RID, ORCID
Kučka, Jan (UMCH-V) RID, ORCID
Rabyk, Mariia (UMCH-V) RID, ORCID
Höcherl, Anita (UMCH-V) RID
Venclíková, Kristýna (UMCH-V) RID
Janoušková, Olga (UMCH-V) RID, SAI, ORCID
Páral, P. (CZ)
Kolářová, V. (CZ)
Heizer, T. (CZ)
Šefc, L. (CZ)
Štěpánek, Petr (UMCH-V) RID, ORCID
Hrubý, Martin (UMCH-V) RID, ORCIDZdroj.dok. Journal of Controlled Release. - : Elsevier - ISSN 0168-3659
Roč. 268, 28 December (2017), s. 78-91Poč.str. 14 s. Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova beta-glucan ; polyoxazoline ; multimodal cancer therapy Vědní obor RIV CF - Fyzikální chemie a teoretická chemie Obor OECD Physical chemistry CEP GA16-02870S GA ČR - Grantová agentura ČR GA16-03156S GA ČR - Grantová agentura ČR NV15-25781A GA MZd - Ministerstvo zdravotnictví 7AMB16FR042 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UMCH-V - RVO:61389013 UT WOS 000417329800008 EID SCOPUS 85031796269 DOI 10.1016/j.jconrel.2017.10.010 Anotace A conceptually new bimodal immunoradiotherapy treatment was demonstrated using thermoresponsive polymer .beta.-glucan-graft-poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline) bearing complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with yttrium-90(III) at the graft ends. The behavior of this thermoresponsive polymer in aqueous solutions was studied, and it showed the appropriate cloud point temperature for brachytherapy applications. The polymer was tested in vitro, and it exhibited nontoxicity and active uptake into cancer cells and macrophages with colocalization in the lysosomes and macrophagosomes. Moreover, the observed oxidative burst response of the leukocytes established the immunostimulatory properties of the polymer, which were also studied in vivo after injection into the thigh muscles of healthy mice. The subsequent histological evaluation revealed the extensive immune activation reactions at the site of injection. Furthermore, the production of tumor necrosis factor .alpha. induced by the prepared polymer was observed in vitro, denoting the optimistic prognosis of the treatment. The biodistribution study in vivo indicated the formation of the polymer depot, which was gradually degraded and excluded from the body. The radiolabeled polymer was used during in vivo antitumor efficiency experiments on mice with EL4 lymphoma. The immunoradiotherapy group (treated with the radiolabeled polymer) demonstrated the complete inhibition of tumor growth during the beginning of the treatment. Moreover, 7 of the 15 mice were completely cured in this group, while the others exhibited significantly prolonged survival time compared to the control group. The in vivo experiments indicated the considerable synergistic effect of using immunoradiotherapy compared to separately using immunotherapy or radiotherapy. Pracoviště Ústav makromolekulární chemie Kontakt Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Rok sběru 2018
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