Targeting drugs selectively to @entity5 cells can potentially benefit @entity5 @entity1 by avoiding side effects generally associated with several @entity5 therapies. One of the attractive approaches to direct the drug cargo to specific sites is to incorporate ligands at the surface of the delivery systems. Integrin a(5)b(1) is overexpressed in @entity5 vasculature and @entity5 cells, thus making it an attractive target for use in drug delivery. Our group has developed a fibronectin-mimetic peptide, PR_b, which has been shown to bind specifically to integrin a(5)b(1), thereby providing a tool to target a(5)b(1)-expressing @entity5 cells in vitro as well as in vivo. Our current work focuses on designing modified stealth liposomes (liposomes functionalized with @entity968 , @entity970 ) for combining the benefits associated with PEGylation, as well as imparting specific targeting properties to the liposomes. We have designed PEGylated liposomes that incorporate in their bilayer the fibronectin-mimetic peptide-amphiphile PR_b that can target several @entity5 cells that overexpress a(5)b(1), including the @entity0 cells used in this study. We have encapsulated @entity632 inside the liposomes to enhance its therapeutic potential via PEGylation as well as active targeting to the @entity5 cells. Our results show that PR_b-functionalized stealth liposomes were able to specifically bind to MDA-MB-231 cells, and the binding could be controlled by varying the peptide concentration. The intracellular trafficking of the @entity632 liposomes was examined, and within minutes after delivery the majority of them were found to be in the early endosomes, whereas after a longer period of time they had accumulated in the late endosomes and lysosomes. The functionalized liposomes were found to be equally cytotoxic as the free @entity632 , especially at higher @entity632 concentrations, and provided higher @entity137 than the nontargeted and GRGDSP-functionalized stealth liposomes. Thus, the PR_b-functionalized PEGylated nanoparticles examined in this study offer a promising strategy to deliver their therapeutic payload directly to the @entity0 cells, in an efficient and specific manner.

PEGylated liposomal @entity632 targeted to a5b1-expressing XXXX cells.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity632 :: ('MESH:D004317', 'Chemical') :: ['doxorubicin'] @entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer', 'MDA-MB-231 breast cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity970 :: ('CHEBI:46793', 'Chemical') :: ['PEG'] @entity968 :: ('MESH:D011092', 'Chemical') :: ['polyethylene glycol']
@entity0 :: (MESH:D001943,Disease) :: ['MDA-MB-231 breast cancer']
