Macromolecular HPMA-Based Nanoparticles with Cholesterol for Solid-Tumor Targeting: Detailed Study of the Inner Structure of a Highly Efficient Drug Delivery System

详细信息    查看全文

• 作者：Sergey K. Filippov ; Petr Chytil ; Petr V. Konarev ; Margarita Dyakonova ; ChristineM. Papadakis ; Alexander Zhigunov ; Josef Plestil ; Petr Stepanek ; Tomas Etrych ; Karel Ulbrich ; Dmitri I. Svergun
• 刊名：Biomacromolecules
• 出版年：2012
• 出版时间：August 13, 2012
• 年：2012
• 卷：13
• 期：8
• 页码：2594-2604
• 全文大小：609K
• 年卷期：v.13,no.8(August 13, 2012)
• ISSN：1526-4602

文摘

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 N_aggr of the nanoparticles grows with increasing cholesterol content. From ab initio calculations, we conclude that the most probable structure of HPMA copolymer鈥揷holesterol 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.