Rational identification of a novel peptide for targeting nanocarriers to 9L glioma.
Traditional therapies for high grade gliomas are limited in part by collateral damage to normal tissues. Selective delivery of therapies to tumors is, therefore, needed. Here, we report that liposomal nanocarriers coated with a novel oligopeptide enhance uptake by 9L gliosarcoma. A targeting nine amino acid peptide sequence (RSI) was identified by differential panning of random peptide phage display libraries on 9L cells and rat blood cells and plasma. Peptides were coupled to the surface of liposomal nanocarriers which were subsequently loaded with doxorubicin. The ability of RSI coated liposomes to facilitate drug uptake and cytotoxicity was compared with conventional liposomal nanocarriers and controls. In addition, plasma clearance profiles of the RSI peptide coupled liposomal nanocarriers were evaluated in adult immuno-competent rats. RSI peptide-coupled liposomal nanocarriers enhanced drug uptake by 9L cells by 500% compared with conventional liposomal nanocarriers, and significantly increased cytotoxicity. The plasma half-lives confirmed that the presence of the RSI peptide on the liposomal nanocarriers did not compromise circulation time in the blood in comparison with Stealth liposomal nanocarriers. These data suggest that phage-identified oligopeptides could lead to the development of new tumor selective nanocarriers.
Agarwal
Abhiruchi
A
Neurological Biomaterials and Therapeutics, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Jaye
David L
DL
Giegerman
Cissy M
CM
Bellamkonda
Ravi V
RV
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000493:pharmacokinetics*; D018316:Gliosarcoma / Q000378:metabolism*; D008081:Liposomes / Q000493:pharmacokinetics*; D008297:Male; D049329:Nanostructures; D010455:Peptides / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D010455:Peptides; D004317:Doxorubicin