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Macromolecular HPMA-based nanoparticles with cholesterol for solid-tumor targeting: detailed study of the inner structure of a highly efficient drug delivery system
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SYSNO ASEP 0379698 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Macromolecular HPMA-based nanoparticles with cholesterol for solid-tumor targeting: detailed study of the inner structure of a highly efficient drug delivery system Tvůrce(i) Filippov, Sergey K. (UMCH-V) RID, ORCID, SAI
Chytil, Petr (UMCH-V) RID, ORCID
Konarev, P. V. (DE)
Dyakonova, M. (DE)
Papadakis, C. M. (DE)
Zhigunov, Alexander (UMCH-V) RID, ORCID
Pleštil, Josef (UMCH-V) RID
Štěpánek, Petr (UMCH-V) RID, ORCID
Etrych, Tomáš (UMCH-V) RID, ORCID
Ulbrich, Karel (UMCH-V) RID
Svergun, D. I. (DE)Zdroj.dok. Biomacromolecules. - : American Chemical Society - ISSN 1525-7797
Roč. 13, č. 8 (2012), s. 2594-2604Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova HPMA ; cholesterol ; SAXS Vědní obor RIV CD - Makromolekulární chemie CEP ME09059 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy IAAX00500803 GA AV ČR - Akademie věd GAP108/12/0640 GA ČR - Grantová agentura ČR Institucionální podpora UMCH-V - RVO:61389013 CEZ AV0Z40500505 - UMCH-V (2005-2011) UT WOS 000307422300044 DOI 10.1021/bm3008555 Anotace We report a rigorous investigation into the detailed structure of nanoparticles already shown to be successful drug delivery nanocarriers. The basic structure of the drug conjugates consists of an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer bearing the anticancer drug doxorubicin (Dox) bound via a pH-sensitive hydrazone bond and a defined amount of cholesterol moieties that vary in hydrophobicity. The results show that size, anisotropy, and aggregation number Naggr of the nanoparticles grows with increasing cholesterol content. From ab initio calculations, we conclude that the most probable structure of HPMA copolymer–cholesterol nanoparticles is a pearl necklace structure, where ellipsoidal pearls mainly composed of cholesterol are covered by a HPMA shell; pearls are connected by bridges composed of hydrophilic HPMA copolymer chains. Using a combination of techniques, we unambiguously show that the Dox moieties are not impregnated inside a cholesterol core but are instead uniformly distributed across the whole nanoparticle, including the hydrophilic HPMA shell surface. Pracoviště Ústav makromolekulární chemie Kontakt Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Rok sběru 2013
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