%0 Journal Article %1 Messerschmidt2009 %A Messerschmidt, Sylvia K.E. %A Musyanovych, Anna %A Altvater, Martin %A Scheurich, Peter %A Pfizenmaier, Klaus %A Landfester, Katharina %A Kontermann, Roland E. %D 2009 %J Journal of Controlled Release %K 2009 izi kontermann pfizenmaier %N 1 %P 69--77 %R 10.1016/j.jconrel.2009.03.010 %T Targeted lipid-coated nanoparticles: Delivery of tumor necrosis factor-functionalized particles to tumor cells %U https://www.ncbi.nlm.nih.gov/pubmed/19306900 %V 137 %X Polymeric nanoparticles displaying tumor necrosis factor on their surface (TNF nanocytes) are useful carrier systems capable of mimicking the bioactivity of membrane-bound TNF. Thus, TNF nanocytes are potent activators of TNF receptor 1 and 2 leading to a striking enhancement of apoptosis. However, in vivo applications are hampered by potential systemic toxicity. Here, using TNF nanocytes as a model system, we developed a procedure to generate targeted lipid-coated particles (TLP) in which TNF activity is shielded. The TLPs generated here are composed of an inner single-chain TNF (scTNF)-functionalized, polymeric nanoparticle core surrounded by a lipid coat endowed with polyethylene glycol (PEG) for sterical stabilization and a single-chain Fv (scFv) fragment for targeting. Using a scFv directed against the tumor stroma marker fibroblast activation protein (FAP) we show that TLP and scTNF-TLP specifically bind to FAP-expressing, but not to FAP-negative cells. Lipid coating strongly reduced nonspecific binding of particles and scTNF-mediated cytotoxicity towards FAP-negative cells. In contrast, an increased cytotoxicity of TLP was observed for FAP-positive cells. Thus, through liposome encapsulation, nanoparticles carrying bioactive molecules, which are subject to nonselective uptake and activity towards various cells and tissues, can be converted into target cell-specific composite particles exhibiting a selective activity towards antigen-positive target cells. Besides safe and targeted delivery of death ligands such as TNF, TLP should be suitable for various diagnostic and therapeutic applications, which benefit from a targeted delivery of reagents embedded into the particle core or displayed on the core particle surface. © 2009 Elsevier B.V. All rights reserved. %7 2009/03/25 %@ 1873-4995 (Electronic)$\backslash$r0168-3659 (Linking)

@article{Messerschmidt2009, abstract = {Polymeric nanoparticles displaying tumor necrosis factor on their surface (TNF nanocytes) are useful carrier systems capable of mimicking the bioactivity of membrane-bound TNF. Thus, TNF nanocytes are potent activators of TNF receptor 1 and 2 leading to a striking enhancement of apoptosis. However, in vivo applications are hampered by potential systemic toxicity. Here, using TNF nanocytes as a model system, we developed a procedure to generate targeted lipid-coated particles (TLP) in which TNF activity is shielded. The TLPs generated here are composed of an inner single-chain TNF (scTNF)-functionalized, polymeric nanoparticle core surrounded by a lipid coat endowed with polyethylene glycol (PEG) for sterical stabilization and a single-chain Fv (scFv) fragment for targeting. Using a scFv directed against the tumor stroma marker fibroblast activation protein (FAP) we show that TLP and scTNF-TLP specifically bind to FAP-expressing, but not to FAP-negative cells. Lipid coating strongly reduced nonspecific binding of particles and scTNF-mediated cytotoxicity towards FAP-negative cells. In contrast, an increased cytotoxicity of TLP was observed for FAP-positive cells. Thus, through liposome encapsulation, nanoparticles carrying bioactive molecules, which are subject to nonselective uptake and activity towards various cells and tissues, can be converted into target cell-specific composite particles exhibiting a selective activity towards antigen-positive target cells. Besides safe and targeted delivery of death ligands such as TNF, TLP should be suitable for various diagnostic and therapeutic applications, which benefit from a targeted delivery of reagents embedded into the particle core or displayed on the core particle surface. {\textcopyright} 2009 Elsevier B.V. All rights reserved.}, added-at = {2023-06-29T13:07:55.000+0200}, author = {Messerschmidt, Sylvia K.E. and Musyanovych, Anna and Altvater, Martin and Scheurich, Peter and Pfizenmaier, Klaus and Landfester, Katharina and Kontermann, Roland E.}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2b29b60a76a405d09fe91bb6800068c3e/fabian}, doi = {10.1016/j.jconrel.2009.03.010}, edition = {2009/03/25}, interhash = {6dc8db255c76938eeb8e2c8f30756cf1}, intrahash = {b29b60a76a405d09fe91bb6800068c3e}, isbn = {1873-4995 (Electronic)$\backslash$r0168-3659 (Linking)}, issn = {01683659}, journal = {Journal of Controlled Release}, keywords = {2009 izi kontermann pfizenmaier}, number = 1, pages = {69--77}, pmid = {19306900}, timestamp = {2023-06-29T13:07:55.000+0200}, title = {{Targeted lipid-coated nanoparticles: Delivery of tumor necrosis factor-functionalized particles to tumor cells}}, url = {https://www.ncbi.nlm.nih.gov/pubmed/19306900}, volume = 137, year = 2009 }