Liposomal doxorubicin doubly functionalized with CCK8 and R8 peptide sequences for selective intracellular drug delivery

Liposomal doxorubicin doubly functionalized with CCK8 and R8 peptide sequences for selective intracellular drug delivery (682 views)

Ringhieri P, Diaferia C, Galdiero S, Palumbo R, Morelli G, Accardo A

J Pept Sci (ISSN: 1075-2617, 1099-1387, 1075-2617linking), 2015; 21(5): 415-425.

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Paper type: Journal Article,

Impact factor: 1.951, 5-year impact factor: 1.707

Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-84928784909&partnerID=40&md5=8f1a25adce5e0b8fc70daf5ee0c6717d

Keywords: Cell-Penetrating Peptides, Click Chemistry, Drug Delivery Systems, Homing Peptides, Liposomes, Cell Penetrating Peptide, Cytokeratin 8, Dithiothreitol, Doxorubicin, R8 Cell Penetrating Peptide, Unclassified Drug, Amino Acid Sequence, Article, Disulfide Bond, Flow Cytometry, Fluorescence Resonance Energy Transfer, Priority Journal, Protein Modification, Protein Synthesis, Target Cell,

Affiliations:
*** IBB - CNR ***

Department of Pharmacy, CIRPeB, Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples 'Federico II', Via Mezzocannone 16, Naples, Italy
IBB, CNR, Via Mezzocannone 16, Naples, Italy
IBB CNR Via Mezzocannone 16 80134 Naples Italy

References:
Not available.

Liposomal doxorubicin doubly functionalized with CCK8 and R8 peptide sequences for selective intracellular drug delivery

A new dual-ligand liposomal doxorubicin delivery system, which couples targeting to enhanced cellular uptake and may lead to a more efficient drug delivery system, is here designed and synthetized. Liposomes based on the composition 1,2-dioleoyl-sn-glycero-3-phosphocholine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-Peg2000-R8/(C18)2-L5-SS-CCK8 (87/8/5 mol/mol/mol) were prepared and loaded with doxorubicin. Presence of the two peptides on the external surface is demonstrated by fluorescence resonance energy transfer assay. The combination of the R8 cell-penetrating peptide and of the CCK8 targeting peptide (homing peptide) on the liposome surface is obtained by combining pre-modification and post-modification methods. In the dual-ligand system, the CCK8 peptide is anchored to the liposome surface by using a disulfide bond. This chemical function is inserted in order to promote the selective cleavage of the homing peptide under the reductive conditions expected in proximity of the tumor site, thus allowing targeting and internalization of the liposomal drug. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

Liposomal doxorubicin doubly functionalized with CCK8 and R8 peptide sequences for selective intracellular drug delivery

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Liposomal doxorubicin doubly functionalized with CCK8 and R8 peptide sequences for selective intracellular drug delivery

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