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Rational identification of a novel peptide for targeting nanocarriers to 9L glioma
Abhiruchi Agarwal1, David L Jaye, Cissy M Giegerman
1Neurological Biomaterials and Therapeutics, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Abstract:
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.
Insights
Novel oligopeptides on liposomal nanocarriers significantly enhance drug delivery to high-grade gliomas. This targeted approach improves cancer therapy by increasing drug uptake and cytotoxicity while maintaining safe circulation times.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- High-grade gliomas pose treatment challenges due to limited efficacy and collateral damage from conventional therapies.
- Selective tumor targeting is crucial for improving therapeutic outcomes and reducing side effects.
Purpose of the Study:
- To develop and evaluate novel oligopeptide-coated liposomal nanocarriers for enhanced delivery of doxorubicin to 9L gliosarcoma.
- To assess the in vivo performance and safety of these targeted nanocarriers.
Main Methods:
- Identification of a nine amino acid targeting peptide (RSI) using phage display technology against 9L gliosarcoma cells.
- Coupling of the RSI peptide to doxorubicin-loaded liposomal nanocarriers.
- In vitro assessment of drug uptake and cytotoxicity in 9L cells.
- In vivo evaluation of plasma clearance profiles in rats.
Main Results:
- RSI peptide-coupled liposomal nanocarriers demonstrated a 500% increase in drug uptake by 9L cells compared to conventional liposomes.
- Significantly enhanced cytotoxicity was observed with the targeted nanocarriers.
- Plasma half-life studies confirmed that the RSI peptide did not negatively impact circulation time.
Conclusions:
- Phage-identified oligopeptides can be effectively utilized to create tumor-selective nanocarriers.
- This novel targeted delivery system shows promise for improving high-grade glioma treatment.
- Further development of oligopeptide-functionalized nanocarriers could lead to more effective and safer cancer therapies.
