title: Polyester-idarubicin nanoparticles and a polymer-photosensitizer complex as potential drug formulations for cell-mediated drug delivery.
abstract: Cell-mediated transport of therapeutics has emerged as promising alternative to classical drug delivery approaches. To preserve viability and functions of carrier cells, encapsulation of active drugs in protective nanoparticles or the use of inducible therapeutics has been proposed. Here, we compared the effects of novel polymeric formulations of an active and a stimulus-sensitive anti-cancer drug on human T lymphocytes to identify suitable drug preparations for cell-mediated drug delivery. For the first approach, the chemotherapeutic agent idarubicin (IDA) was encapsulated in poly(lactic-co-glycolic-acid) (PLGA) and newly developed maleate-polyester (MPE) nanoparticles. PLGA- and MPE-encapsulated IDA was efficiently internalized by ex vivo activated human T lymphocytes; however, both encapsulations could not prevent premature T cell death resulting from IDA-uptake. In contrast, loading with a poly(styrene sulfonate) (PSS)-complex of the light-sensitive pharmaceutical 5,10,15,20-tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP) did not affect T cell viability if upon loading the cells were kept in the dark. The photosensitizer was transferred from loaded T lymphocytes to co-cultivated carcinoma cells, and induced cancer cell death if co-cultures were exposed to light. Inducible drugs, such as photosensitizers, thus, may help to overcome the limitations of encapsulated active drugs and open up new perspectives for the use of cells as drug transporters in cancer therapy.
authors.affiliation: Cellular Immunotherapy Team and Environment and Bio Group, Korea Institute of Science and Technology (KIST) Europe, Saarbrücken 66123, Germany.
authors.forename: André-R
authors.initials: AR
authors.lastname: Blaudszun
authors.affiliation: Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken 66123, Germany.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lian
authors.affiliation: Organic Macromolecular Chemistry, Saarland University, Saarbrücken 66123, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schnabel
authors.affiliation: Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken 66123, Germany; Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken 66123, Germany.
authors.forename: Brigitta
authors.initials: B
authors.lastname: Loretz
authors.affiliation: Cellular Immunotherapy Team and Environment and Bio Group, Korea Institute of Science and Technology (KIST) Europe, Saarbrücken 66123, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Steinfeld
authors.affiliation: Cellular Immunotherapy Team and Environment and Bio Group, Korea Institute of Science and Technology (KIST) Europe, Saarbrücken 66123, Germany.
authors.forename: Hyeck-H
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Organic Macromolecular Chemistry, Saarland University, Saarbrücken 66123, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wenz
authors.affiliation: Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken 66123, Germany; Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken 66123, Germany.
authors.forename: Claus-M
authors.initials: CM
authors.lastname: Lehr
authors.affiliation: Pharmaceutical Nanotechnology, Saarland University, Saarbrücken 66123, Germany; Pharmaceutics and Biopharmacy, Philipps University Marburg, Marburg 35032, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Cellular Immunotherapy Team and Environment and Bio Group, Korea Institute of Science and Technology (KIST) Europe, Saarbrücken 66123, Germany. Electronic address: a.philippi@kist-europe.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Philippi
mesh_terms: D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D006801:Humans; D015255:Idarubicin / Q000737:chemistry*; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D017319:Photosensitizing Agents / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D013499:Surface Properties; D013601:T-Lymphocytes / Q000737:chemistry
chemical_list: D017319:Photosensitizing Agents; D011108:Polymers; D015255:Idarubicin
keywords: Gold shell nanoparticle; Photosensitizer; Polymeric nanoparticle; T lymphocyte; Targeted drug delivery