Target delivery to a desirable site of action is one of the most crucial issue in cancer therapy. Nanoparticles are regarded to be ideal vehicles for antitumor drug because their hydrophobic inner core is an appropriate reservoir for hydrophobic anticancer drugs, moreover their hydrophilic outer shell facilitates long blood circulation, and the improvement of enhanced permeation and retention [EPR] effect in tumor tissue. Delivery improvement can be obtained by labelling nanoparticles with bioactive moiety like antibodies, organic molecules and peptides able to recognize tumor cells overexpressing receptors1. Epidermal growth factor receptor (EGFR) is a promising target site for cancer therapy since it is high-expressed in several kinds of tumors such as lung cancer, ovarian cancer and hepatocellular carcinoma. The aim of this study is to construct and evaluate GE11 peptide modified micelles for targeted delivery of sorafenib to EGFR-positive cells. Sorafenib is a high hydrophobic chemotherapeutic agent that inhibits tumor cell proliferation and vascularization3. The amino acid sequence YHWYGYTPQNVI (designated as GE11 peptide) was selected in literature as ligand with specific binding capabilities to EGFR by phage display peptide library4 and it was conjugated to hydrophobic moiety thought ethoxylic linkers. The amphiphilic surfactant pluronic F127 was added to the peptide derivative in order to obtain mixed peptide-labelled micelles. Sorafenib payload was fine tuning with emulsion method achiving high loading ratio. The physicochemical properties of these targeted micelles, including unloaded and loaded drug, such as particle size and polydispersity index, were examined by dynamic light scattering (DLS) measurements. Micelle cell uptake was investigated on human hepatocellular carcinoma (HCC) PLC/PRF/5 cells overexpressing EGF receptors and related to HCC EGFR-negative HepG2 cells. The future aims will be to evaluate the antitumor activity of sorafenib-incorporated nanoparticles on the same cell lines.

EGF analog peptide fuctionalized micelles for target selective sorafenib delivery

RINGHIERI, PAOLA;MORELLI, GIANCARLO
Conceptualization
;
TESAURO, DIEGO
Conceptualization
2014

Abstract

Target delivery to a desirable site of action is one of the most crucial issue in cancer therapy. Nanoparticles are regarded to be ideal vehicles for antitumor drug because their hydrophobic inner core is an appropriate reservoir for hydrophobic anticancer drugs, moreover their hydrophilic outer shell facilitates long blood circulation, and the improvement of enhanced permeation and retention [EPR] effect in tumor tissue. Delivery improvement can be obtained by labelling nanoparticles with bioactive moiety like antibodies, organic molecules and peptides able to recognize tumor cells overexpressing receptors1. Epidermal growth factor receptor (EGFR) is a promising target site for cancer therapy since it is high-expressed in several kinds of tumors such as lung cancer, ovarian cancer and hepatocellular carcinoma. The aim of this study is to construct and evaluate GE11 peptide modified micelles for targeted delivery of sorafenib to EGFR-positive cells. Sorafenib is a high hydrophobic chemotherapeutic agent that inhibits tumor cell proliferation and vascularization3. The amino acid sequence YHWYGYTPQNVI (designated as GE11 peptide) was selected in literature as ligand with specific binding capabilities to EGFR by phage display peptide library4 and it was conjugated to hydrophobic moiety thought ethoxylic linkers. The amphiphilic surfactant pluronic F127 was added to the peptide derivative in order to obtain mixed peptide-labelled micelles. Sorafenib payload was fine tuning with emulsion method achiving high loading ratio. The physicochemical properties of these targeted micelles, including unloaded and loaded drug, such as particle size and polydispersity index, were examined by dynamic light scattering (DLS) measurements. Micelle cell uptake was investigated on human hepatocellular carcinoma (HCC) PLC/PRF/5 cells overexpressing EGF receptors and related to HCC EGFR-negative HepG2 cells. The future aims will be to evaluate the antitumor activity of sorafenib-incorporated nanoparticles on the same cell lines.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/598807
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