The TNF-related apoptosis-inducing ligand (TRAIL) is a powerful inducer of apoptosis in tumor cells; however, clinical studies with recombinant soluble TRAIL were rather disappointing. Here, we developed TRAIL-functionalized liposomes (LipoTRAIL, LT) to mimic membrane-displayed TRAIL for efficient activation of death receptors DR4 and DR5 and enhanced induction of apoptosis, which were combined with an anti-EGFR single-chain Fv fragment (scFv) for targeted delivery to EGFR-positive tumor cells. These immuno-LipoTRAILs (ILTs) bound specifically to EGFR-expressing cells (Colo205) and exhibited increased cytotoxicity compared with that of nontargeted LTs. Compared to that of the soluble TRAIL, the plasma half-life of the functionalized liposomes was strongly extended, and increased antitumor activity of LT and ILT was demonstrated in a xenograft tumor model. Thus, we established a multifunctional liposomal TRAIL formulation (ILT) with improved pharmacokinetic and pharmacodynamic behavior, characterized by targeted delivery and increased induction of apoptosis due to multivalent TRAIL presentation.
%0 Journal Article
%1 Seifert2014a
%A Seifert, Oliver
%A Pollak, Nadine
%A Nusser, Anja
%A Steiniger, Frank
%A Rüger, Ronny
%A Pfizenmaier, Klaus
%A Kontermann, Roland E.
%D 2014
%J Bioconjugate Chemistry
%K 2014 izi kontermann pfizenmaier
%N 5
%P 879--887
%R 10.1021/bc400517j
%T Immuno-LipoTRAIL: Targeted delivery of TRAIL-functionalized liposomal nanoparticles
%U http://www.ncbi.nlm.nih.gov/pubmed/24766622
%V 25
%X The TNF-related apoptosis-inducing ligand (TRAIL) is a powerful inducer of apoptosis in tumor cells; however, clinical studies with recombinant soluble TRAIL were rather disappointing. Here, we developed TRAIL-functionalized liposomes (LipoTRAIL, LT) to mimic membrane-displayed TRAIL for efficient activation of death receptors DR4 and DR5 and enhanced induction of apoptosis, which were combined with an anti-EGFR single-chain Fv fragment (scFv) for targeted delivery to EGFR-positive tumor cells. These immuno-LipoTRAILs (ILTs) bound specifically to EGFR-expressing cells (Colo205) and exhibited increased cytotoxicity compared with that of nontargeted LTs. Compared to that of the soluble TRAIL, the plasma half-life of the functionalized liposomes was strongly extended, and increased antitumor activity of LT and ILT was demonstrated in a xenograft tumor model. Thus, we established a multifunctional liposomal TRAIL formulation (ILT) with improved pharmacokinetic and pharmacodynamic behavior, characterized by targeted delivery and increased induction of apoptosis due to multivalent TRAIL presentation.
@article{Seifert2014a,
abstract = {The TNF-related apoptosis-inducing ligand (TRAIL) is a powerful inducer of apoptosis in tumor cells; however, clinical studies with recombinant soluble TRAIL were rather disappointing. Here, we developed TRAIL-functionalized liposomes (LipoTRAIL, LT) to mimic membrane-displayed TRAIL for efficient activation of death receptors DR4 and DR5 and enhanced induction of apoptosis, which were combined with an anti-EGFR single-chain Fv fragment (scFv) for targeted delivery to EGFR-positive tumor cells. These immuno-LipoTRAILs (ILTs) bound specifically to EGFR-expressing cells (Colo205) and exhibited increased cytotoxicity compared with that of nontargeted LTs. Compared to that of the soluble TRAIL, the plasma half-life of the functionalized liposomes was strongly extended, and increased antitumor activity of LT and ILT was demonstrated in a xenograft tumor model. Thus, we established a multifunctional liposomal TRAIL formulation (ILT) with improved pharmacokinetic and pharmacodynamic behavior, characterized by targeted delivery and increased induction of apoptosis due to multivalent TRAIL presentation.},
added-at = {2018-02-01T14:44:29.000+0100},
author = {Seifert, Oliver and Pollak, Nadine and Nusser, Anja and Steiniger, Frank and R{\"{u}}ger, Ronny and Pfizenmaier, Klaus and Kontermann, Roland E.},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/23c8b11ffd4fb40227fe762877205c8df/cristiano},
doi = {10.1021/bc400517j},
interhash = {7b787e72c6fbfdbe20e9d5da2b89a01a},
intrahash = {3c8b11ffd4fb40227fe762877205c8df},
issn = {15204812},
journal = {Bioconjugate Chemistry},
keywords = {2014 izi kontermann pfizenmaier},
month = may,
number = 5,
pages = {879--887},
pmid = {24766622},
timestamp = {2019-01-17T12:53:59.000+0100},
title = {{Immuno-LipoTRAIL: Targeted delivery of TRAIL-functionalized liposomal nanoparticles}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24766622},
volume = 25,
year = 2014
}
