Macromolecular HPMA-based nanoparticles with cholesterol for solid-tumor targeting: detailed study of the inner structure of a highly efficient drug delivery system

0379698 - ÚMCH 2013 RIV US eng J - Journal Article
Filippov, Sergey K. - Chytil, Petr - Konarev, P. V. - Dyakonova, M. - Papadakis, C. M. - Zhigunov, Alexander - Pleštil, Josef - Štěpánek, Petr - Etrych, Tomáš - Ulbrich, Karel - Svergun, D. I.
Macromolecular HPMA-based nanoparticles with cholesterol for solid-tumor targeting: detailed study of the inner structure of a highly efficient drug delivery system.
Biomacromolecules. Roč. 13, č. 8 (2012), s. 2594-2604. ISSN 1525-7797. E-ISSN 1526-4602
R&D Projects: GA MŠMT ME09059; GA AV ČR IAAX00500803; GA ČR GAP108/12/0640
Institutional research plan: CEZ:AV0Z40500505
Institutional support: RVO:61389013
Keywords : HPMA * cholesterol * SAXS
Subject RIV: CD - Macromolecular Chemistry
Impact factor: 5.371, year: 2012

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.
Permanent Link: http://hdl.handle.net/11104/0007113