EphA2 Targeted Doxorubicin-Nanoliposomes for Osteosarcoma Treatment.

Abstract

PURPOSE:

To employ Doxorubicin-loaded liposomes, modified with YSA-peptide to target EphA2, to reduce adverse effects against primary bone cells and maximize toxicity against Saos-2 osteosarcoma cells.

METHODS:

PEGylated liposomes were prepared by thin film method using Dipalmitoylphosphatidylcholine (DPPC), cholesterol and distearylphosphatidylethanolamine-polyethyleneglycol conjugate (DSPE-mPEG) in 67.9:29.1:3 M ratios, and loaded with DOX (L-DOX) by pH-gradient method. Targeted liposomes (YSA-L-DOX), were prepared by conjugating YSA-peptide to DSPE-mPEG. Liposomes were physicochemically characterized and tested in cellular toxicity assays.

RESULTS:

YSA conjugation efficiency was >98%. Size and polydispersity index of both L-DOX and YSA-L-DOX were around 88 nm and 0.188, respectively. Both had similar zeta potential, and 85% DOX loading efficiencies. DOX release kinetics followed the Korsmeyer-Peppa model, and showed comparable release for both formulations from 1-8 h, and a plateau of 29% after 48 h. Both formulations could be stably stored for ≥6 months at 4°C in the dark. Toxicity assays showed a significant 1.91-fold higher cytotoxicity compared to free DOX in the Saos-2 cells, and 2-fold lesser toxicity in primary bone cells compared to the Saos-2 cells. Cellular uptake studies showed higher and more nuclear uptake in YSA-L-DOX compared to L-DOX treated cells.

CONCLUSIONS:

YSA-L-DOX vesicles might be effective for targeted treatment of osteosarcoma.

• Authors: Fateme Haghiralsadat, Ghasem Amoabediny, Samira Naderinezhad, Kamran Nazmi, Jantine Posthuma De Boer, Behrouz Zandieh-Doulabi, Tymour Forouzanfar, Marco N Helder
• Journal: Pharmaceutical research (Pharm Res) Vol. 34 Issue 12 Pg. 2891-2900 (Dec 2017) ISSN: 1573-904X [Electronic] United States
• PMID: 29110283 (Publication Type: Journal Article)

Chemical References

• Antibiotics, Antineoplastic
• Liposomes
• Peptides
• liposomal doxorubicin
• Polyethylene Glycols
• Doxorubicin
• Receptor, EphA2

Topics

• Antibiotics, Antineoplastic (administration & dosage, pharmacology)
• Bone Neoplasms (drug therapy, metabolism)
• Cell Line, Tumor
• Doxorubicin (administration & dosage, analogs & derivatives, pharmacology)
• Drug Delivery Systems
• Humans
• Liposomes (chemistry)
• Osteosarcoma (drug therapy, metabolism)
• Peptides (chemistry)
• Polyethylene Glycols (administration & dosage, chemistry, pharmacology)
• Receptor, EphA2 (metabolism)