Macromolecular HPMA-based nanoparticles with cholesterol for solid-tumor targeting: detailed study of the inner structure of a highly efficient drug delivery system
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22793269
DOI
10.1021/bm3008555
Knihovny.cz E-resources
- MeSH
- Acrylamides chemistry MeSH
- Algorithms MeSH
- Anisotropy MeSH
- Cholesterol MeSH
- X-Ray Diffraction MeSH
- Doxorubicin analogs & derivatives chemistry MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Macromolecular Substances chemistry MeSH
- Scattering, Small Angle MeSH
- Micelles MeSH
- Molecular Conformation MeSH
- Models, Molecular MeSH
- Nanocapsules chemistry MeSH
- Neutron Diffraction MeSH
- Antibiotics, Antineoplastic chemistry MeSH
- Light MeSH
- Particle Size MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acrylamides MeSH
- Cholesterol MeSH
- Doxorubicin MeSH
- Macromolecular Substances MeSH
- Micelles MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Browser
- Nanocapsules MeSH
- Antibiotics, Antineoplastic MeSH
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-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.
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