Transferrin Adsorption onto PLGA Nanoparticles Governs Their Interaction with Biological Systems from Blood Circulation to Brain Cancer Cells

• Published in: Pharmaceutical research 2012-06, Vol.29 (6), p.1495-1505
• Main Authors: Chang, Jiang, Paillard, Archibald, Passirani, Catherine, Morille, Marie, Benoit, Jean-Pierre, Betbeder, Didier, Garcion, Emmanuel
• Format: Article
• Language: English
• Subjects: Adsorption; Animals; Antitumor agents; Astrocytes; Astrocytes - metabolism; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Blood circulation; Blood-Brain Barrier - metabolism; Bovine serum albumin; Brain cancer; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain tumors; Capillary Permeability; Caveolae - metabolism; Cell Line, Tumor; Chemistry, Pharmaceutical; Clathrin - metabolism; Coatings; Data processing; Drug Carriers; Drug Compounding; Endocytosis; Female; General pharmacology; Glioblastoma; Glioma - metabolism; Glioma - pathology; Glioma cells; Half-Life; Injections, Intravenous; Lactic Acid - administration & dosage; Lactic Acid - blood; Lactic Acid - chemistry; Lactic Acid - pharmacokinetics; Macrophages; Macrophages - metabolism; Medical Law; Medical sciences; Mice; Monocytes; Monocytes - metabolism; Nanoparticles; Nanotechnology; Nervous system; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Polyglycolic Acid - administration & dosage; Polyglycolic Acid - chemistry; Polyglycolic Acid - pharmacokinetics; polylactide-co-glycolide; Rats; Rats, Inbred F344; Receptors, Transferrin - metabolism; Research Paper; Technology, Pharmaceutical - methods; Tissue Distribution; Transferrin; Transferrin - administration & dosage; Transferrin - chemistry; Transferrin - pharmacokinetics; Tumors; Zeta potential
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-011-0624-1

ABSTRACT Purpose 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. Methods NPs were studied for size, zeta potential, blood half-life, in vitro endocytic behavior and in vivo accumulation within healthy rat brain and brain tumors. Results 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 in vitro . Increase of Tf-NP uptake by F98 cells through caveolae- and clathrin-mediated pathways supports specific interaction between Tf and overexpressed Tf-receptor. Finally, in vivo targeting of healthy brain was found higher with Tf-NPs than with BSA-NPs while both NPs entered massively within brain-developed tumors. Conclusion 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.