Journal
PHARMACEUTICAL RESEARCH
Volume 29, Issue 6, Pages 1495-1505Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-011-0624-1
Keywords
blood-brain barrier; central nervous system; glioma; PLGA nanocarriers; stealth; targeting
Funding
- Le Comite Departemental de Maine-et-Loire de la Ligue Contre le Cancer
- La Ligue Nationale Contre le Cancer through an Equipe Labellisee
- Canceropole Grand-Ouest
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Nanomedicines represent an alternative for the treatment of aggressive glioblastoma tumors. Behaviour of PLGA-nanoparticles (NPs) was here investigated as a function of their protein adsorption characteristics at the different biological interfaces they are expected to face in order to reach brain cancer cells. NPs were studied for size, zeta potential, blood half-life, endocytic behavior and accumulation within healthy rat brain and brain tumors. While slightly modifying size (80 to 90 nm) and zeta potential (-44 to -32 mV) protein coating of PLGA-NPs by bovine serum albumin (BSA) or transferrin (Tf) greatly prolonged their blood half-life when intravenously injected in rats and mice. In contrast with THP-1 monocytes, differentiated THP-1 macrophages, F98 glioma cells and astrocytes internalized BSA- and Tf-NPs . Increase of Tf-NP uptake by F98 cells through caveolae- and clathrin-mediated pathways supports specific interaction between Tf and overexpressed Tf-receptor. Finally, targeting of healthy brain was found higher with Tf-NPs than with BSA-NPs while both NPs entered massively within brain-developed tumors. Taken together, those data evidence that Tf-NPs represent an interesting nanomedicine to deliver anticancer drugs to glioma cells through systemic or locoregional strategies at early and late tumor stages.
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