Počet záznamů: 1
Overcoming multidrug resistance using folate receptor-targeted and pH-responsive polymeric nanogels containing covalently entrapped doxorubicin
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SYSNO ASEP 0476593 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Overcoming multidrug resistance using folate receptor-targeted and pH-responsive polymeric nanogels containing covalently entrapped doxorubicin Tvůrce(i) Chen, Y. (NL)
Tezcan, O. (DE)
Li, D. (NL)
Beztsinna, N. (NL)
Lou, B. (NL)
Etrych, Tomáš (UMCH-V) RID, ORCID
Ulbrich, Karel (UMCH-V) RID
Metselaar, J. M. (NL)
Lammers, T. (NL)
Hennink, W. E. (NL)Zdroj.dok. Nanoscale. - : Royal Society of Chemistry - ISSN 2040-3364
Roč. 9, č. 29 (2017), s. 10404-10419Poč.str. 16 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova drug delivery ; doxorubicin ; pH controlled release Vědní obor RIV CD - Makromolekulární chemie Obor OECD Polymer science CEP LO1507 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UMCH-V - RVO:61389013 UT WOS 000406374000031 EID SCOPUS 85026446524 DOI 10.1039/C7NR03592F Anotace Multidrug resistance (MDR) contributes to failure of chemotherapy. We here show that biodegradable polymeric nanogels are able to overcome MDR via folic acid targeting. The nanogels are based on hydroxyethyl methacrylamide-oligoglycolates-derivatized poly(hydroxyethyl methacrylamide-co-N-(2-azidoethyl)methacrylamide) (p(HEMAm-co-AzEMAm)-Gly-HEMAm), covalently loaded with the chemotherapeutic drug doxorubicin (DOX) and subsequently decorated with a folic acid-PEG conjugate via copper-free click chemistry. pH-Responsive drug release is achieved via the acid-labile hydrazone bond between DOX and the methacrylamide polymeric network. Cellular uptake and cytotoxicity analyses in folate receptor-positive B16F10 melanoma versus folate receptor-negative A549 lung carcinoma cells confirmed specific uptake of the targeted nanogels. Confocal microscopy demonstrated efficient internalization, lysosomal trafficking, drug release and nuclear localization of DOX. We also show that DOX resistance in 4T1 breast cancer cells results in upregulation of the folate receptor, and that folic acid targeted nanogels can be employed to bypass drug efflux pumps, resulting in highly efficient killing of resistant cancer cells. In conclusion, folic acid functionalized nanogels with pH-controlled drug release seem to hold significant potential for treating multidrug resistant malignancies. Pracoviště Ústav makromolekulární chemie Kontakt Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Rok sběru 2018
Počet záznamů: 1