title: Peptide-labeled supramolecular aggregates as selective doxorubicin carriers for delivery to tumor cells.
abstract: New liposomal aggregates, prepared by combining together, in a 90:10 molar ratio, two amphiphilic monomers, one containing two hydrocarbon chains in the hydrophobic region and the anionic DOTA chelating agent as hydrophilic moiety, and the other containing the same hydrophobic moiety and the CCK8 peptide, are described. The liposomal aggregates because of the presence of the specific moiety, constituted by the CCK8 peptide, which selectively recognizes CCK receptors on tumor cells are used as drug carriers with the aim to deliver into tumor cells the appropriate antitumor drug. The drug loading content and the releasing properties of the liposomal aggregates are studied by the use of the cytotoxic doxorubicin as drug model. The doxorubicin loading content determination reveals that above 95% of the total drug was uptaken with a corresponding drug/lipid w/w ratio of 0.134. The cellular uptake of the targeted liposomal doxorubicin with respect to the self-assembled, nonspecific, liposomal doxorubicin is evaluated using flow cytometry assays. The doxorubicin cell content for two types of cell systems, namely, A431 and HuVEC cells, for peptide derivatized liposomes was 70- and 8-fold higher, respectively, than for nontargeted liposomes, indicating that the bioactive CCK8 peptide is able to enhance the doxorubicin uptake into the carcinoma cells in vitro. The cytotoxicity effect of liposomal doxorubicin on A431 cells has been assessed by MTT assays: in presence of drug amounts ranged between 250 and 1000 ng/ml, incubation with peptide derivatized liposomes showed significantly lower cell survival compared with nontargeted liposomes.
authors.affiliation: Department of Biological Sciences, CIRPeB, University of Naples Federico II & IBB-CNR, Via Mezzocannone 16, 80134 Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Morisco
authors.forename: Antonella
authors.initials: A
authors.lastname: Accardo
authors.forename: Diego
authors.initials: D
authors.lastname: Tesauro
authors.forename: Rosanna
authors.initials: R
authors.lastname: Palumbo
authors.forename: Ettore
authors.initials: E
authors.lastname: Benedetti
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Morelli
mesh_terms: D000595:Amino Acid Sequence; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005434:Flow Cytometry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000737:chemistry*; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D012844:Sincalide / Q000737:chemistry / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D006573:Heterocyclic Compounds, 1-Ring; D008081:Liposomes; D010455:Peptides; D011949:Receptors, Cholecystokinin; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D004317:Doxorubicin; D012844:Sincalide