Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy.

Abstract

Selective drug delivery is an important approach with great potential for overcoming problems associated with the systemic toxicity and poor bioavailability of antineoplastic drugs. Nanomedicine plays a pivotal role by delivering drugs in a targeted manner to the malignant tumor cells thereby reducing the systemic toxicity of the anticancer drugs. The objective of this study was to prepare and characterize rapamycin loaded polymeric poly(lactide-co-glycolide) (PLGA) nanoparticles (NP) that were surface conjugated with antibodies to epidermal growth factor receptor (EGFR), highly expressed on breast cancer cells, using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) mediated cross linking agents. To potentiate the anticancer efficiency of the formulations, in vitro cytotoxicity of native rapamycin, rapamycin loaded nanoparticles and EGFR antibody conjugated rapamycin loaded nanoparticles (EGFR-Rapa-NPs) were evaluated on malignant MCF 7 breast cancer cell lines. IC(50) doses as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay showed the superior antiproliferative activity of EGFR-Rapa-NPs over unconjugated nanoparticles and native rapamycin due to higher cellular uptake on malignant breast cancer cells. Cell cycle arrest and cellular apoptosis induced by the above formulations were confirmed by flow cytometry. Molecular basis of apoptosis studied by western blotting revealed the involvement of a cytoplasmic protein in activating the programmed cell death pathway. Thus it was concluded that EGFR-Rapa-NPs provide an efficient and targeted delivery of anticancer drugs, presenting a promising active targeting carrier for tumor selective therapeutic treatment in near future.

• Authors: Sarbari Acharya, Fahima Dilnawaz, Sanjeeb K Sahoo
• Journal: Biomaterials (Biomaterials) Vol. 30 Issue 29 Pg. 5737-50 (Oct 2009) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 19631377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Drug Carriers
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• ErbB Receptors
• Sirolimus

Topics

• Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics)
• Breast Neoplasms (drug therapy, metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Carriers (chemical synthesis)
• ErbB Receptors (antagonists & inhibitors)
• Female
• Humans
• Lactic Acid (chemistry)
• Materials Testing
• Nanostructures (chemistry, therapeutic use, ultrastructure)
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Sirolimus (administration & dosage, pharmacokinetics)