EGFR-Targeted Polymeric Mixed Micelles Carrying Gemcitabine for Treating Pancreatic Cancer.

Abstract

The objective of this study was to design GE11 peptide (YHWYGYTPQNVI) linked micelles of poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-gemcitabine-graft-dodecanol (PEG-b-PCC-g-GEM-g-DC) for enhanced stability and target specificity of gemcitabine (GEM) to EGFR-positive pancreatic cancer cells. GE11-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC mixed micelles showed EGFR-dependent enhanced cellular uptake, and cytotoxicity as compared to scrambled peptide HW12-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC mixed micelles and unmodified mPEG-b-PCC-g-GEM-g-DC micelles. Importantly, GE11-linked mixed micelles preferentially accumulated in orthotopic pancreatic tumor and tumor vasculature at 24 h post systemic administration. GE11-linked mixed micelles inhibited orthotopic pancreatic tumor growth compared to HW12-linked mixed micelles, unmodified mPEG-b-PCC-g-GEM-g-DC micelles, and free GEM formulations. Tumor growth inhibition was mediated by apoptosis of tumor cells and endothelial cells as determined by immunohistochemical staining. In summary, GE11-linked mixed micelles is a promising approach to treat EGFR overexpressing cancers.

• Authors: Goutam Mondal, Virender Kumar, Surendra K Shukla, Pankaj K Singh, Ram I Mahato
• Journal: Biomacromolecules (Biomacromolecules) Vol. 17 Issue 1 Pg. 301-13 (Jan 11 2016) ISSN: 1526-4602 [Electronic] United States
• PMID: 26626700 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Drug Carriers
• GE11 peptide
• Micelles
• Peptides
• Polyesters
• Polymers
• poly(ethylene glycol)-block-poly(2-methyl-2-carboxylpropylene carbonate-graft-dodecanol)
• Deoxycytidine
• Polyethylene Glycols
• monomethoxypolyethylene glycol
• EGFR protein, human
• ErbB Receptors
• Gemcitabine

Topics

• Animals
• Antimetabolites, Antineoplastic (administration & dosage, therapeutic use)
• Carcinoma, Pancreatic Ductal (drug therapy)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Deoxycytidine (administration & dosage, analogs & derivatives, therapeutic use)
• Disease Models, Animal
• Drug Carriers (chemical synthesis, therapeutic use)
• ErbB Receptors (antagonists & inhibitors)
• Humans
• Mice
• Micelles
• Pancreatic Neoplasms (drug therapy)
• Peptides (chemistry)
• Polyesters (chemistry)
• Polyethylene Glycols (chemistry)
• Polymers (chemistry)
• Gemcitabine