Philip Grossen
University of Basel
EndosomeColloidal goldGenetic enhancementPharmacokineticsAsialoglycoprotein receptorBiophysicsTargeted drug deliveryDrug carrierGene deliverySurface plasmonNanomaterialsInternalizationGreen fluorescent proteinFluorescence correlation spectroscopyDynamic light scatteringGene expressionNanomedicineMolecular biologyNanoparticleNanotechnologyNanocarriersKinaseLiposomeChemistryLimitingNanoreactorMaterials scienceIn vitroIn vivoEx vivoSLC10A1ZebrafishBiocompatibilityEthylene glycolBiodistributionHepatocellular carcinomaTherapeutic approachMacrophageExtravasationParvovirusDrug deliveryDrugContext (language use)MTT assayHepatic Asialoglycoprotein ReceptorSodium taurocholate cotransporting polypeptideBiological modelingImaging modalitiesViral geneExpression vectorIn vitro toxicologyComputer scienceCancer researchPolymersomePolymerTransfectionPEG ratioDNAFlow cytometryBiochemistryDrug developmentComputational biologyMedicineDrug discoveryMyristoylationCell cultureMicrofluidicsBiologyCell biologyPharmacology
11Publications
8H-index
370Citations
Publications 11
Newest
#1Dominik Witzigmann (University of Basel)H-Index: 16
#2Philip Grossen (University of Basel)H-Index: 8
Last. Jörg Huwyler (University of Basel)H-Index: 49
view all 18 authors...
Abstract Hepatocellular carcinoma (HCC) is related to increasing incidence rates and poor clinical outcomes due to lack of efficient treatment options and emerging resistance mechanisms. The aim of the present study is to exploit a non-viral gene therapy enabling the expression of the parvovirus-derived oncotoxic protein NS1 in HCC. This anticancer protein interacts with different cellular kinases mediating a multimodal host-cell death. Lipoplexes (LPX) designed to deliver a DNA expression plasm...
Source
#1Sandro Sieber (University of Basel)H-Index: 9
#2Philip Grossen (University of Basel)H-Index: 8
Last. Jörg Huwyler (University of Basel)H-Index: 49
view all 7 authors...
Abstract The interactions of nanomedicines with biological environments is heavily influenced by their physicochemical properties. Formulation design and optimization are therefore key steps towards successful nanomedicine development. Unfortunately, detailed assessment of nanomedicine formulations, at a macromolecular level, in rodents is severely limited by the restricted imaging possibilities within these animals. Moreover, rodent in vivo studies are time consuming and expensive, limiting the...
31 CitationsSource
#1Dominik Witzigmann (University of Basel)H-Index: 16
#2Philipp Uhl (University Hospital Heidelberg)H-Index: 7
Last. Jörg Huwyler (University of Basel)H-Index: 49
view all 16 authors...
: Active targeting and specific drug delivery to parenchymal liver cells is a promising strategy to treat various liver disorders. Here, we modified synthetic lipid-based nanoparticles with targeting peptides derived from the hepatitis B virus large envelope protein (HBVpreS) to specifically target the sodium-taurocholate cotransporting polypeptide (NTCP; SLC10A1) on the sinusoidal membrane of hepatocytes. Physicochemical properties of targeted nanoparticles were optimized and NTCP-specific, lig...
7 CitationsSource
#1Sandro Sieber (University of Basel)H-Index: 9
#2Philip Grossen (University of Basel)H-Index: 8
Last. Jörg Huwyler (University of Basel)H-Index: 49
view all 7 authors...
Abstract Macrophage recognition of nanoparticles is highly influenced by particle size and surface modification. Due to the lack of appropriate in vivo screening models, it is still challenging and time-consuming to characterize and optimize nanomedicines regarding this undesired clearance mechanism. Therefore, we validate zebrafish embryos as an emerging vertebrate screening tool to assess the macrophage sequestration of surface modified particulate formulations with varying particle size under...
20 CitationsSource
#1Jonas Buck (University of Basel)H-Index: 3
#2Philip Grossen (University of Basel)H-Index: 8
Last. Dominik Witzigmann (University of Basel)H-Index: 16
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Gene therapy is a promising strategy for the treatment of monogenic disorders. Non-viral gene delivery systems including lipid-based DNA therapeutics offer the opportunity to deliver an encoding gene sequence specifically to the target tissue and thus enable the expression of therapeutic proteins in diseased cells. Currently, available gene delivery approaches based on DNA are inefficient and require improvements to achieve clinical utility. In this Review, we discuss state-of-the-art lipid-base...
64 CitationsSource
#1Dominik Witzigmann (University of Basel)H-Index: 16
#2Philipp Uhl (University Hospital Heidelberg)H-Index: 7
Last. Jörg Huwyler (University of Basel)H-Index: 49
view all 16 authors...
Source
#1Sandro Sieber (University of Basel)H-Index: 9
#2Philip Grossen (University of Basel)H-Index: 8
Last. Jörg Huwyler (University of Basel)H-Index: 49
view all 6 authors...
Abstract Nanomedicines have gained much attention for the delivery of small molecules or nucleic acids as treatment options for many diseases. However, the transfer from experimental systems to in vivo applications remains a challenge since it is difficult to assess their circulation behavior in the body at an early stage of drug discovery. Thus, innovative and improved concepts are urgently needed to overcome this issue and to close the gap between empiric nanoparticle design, in vitro assessme...
40 CitationsSource
#1Klara Kiene (University of Basel)H-Index: 3
#2Susanne H. Schenk (University of Basel)H-Index: 8
Last. Jörg Huwyler (University of Basel)H-Index: 49
view all 7 authors...
Abstract Nanoparticles, such as polymersomes, can be directed to the hepatic asialoglycoprotein receptor to achieve targeted drug delivery. In this study, we prepared asialofetuin conjugated polymersomes based on the amphiphilic di-block copolymer poly(dimethylsiloxane)- b -poly(2-methyloxazoline) (PDMS- b -PMOXA). They had an average diameter of 150 nm and formed monodisperse vesicles. Drug encapsulation and sustained release was monitored using the hydrophilic model compound carboxyfluorescein...
16 CitationsSource
#1Philip Grossen (University of Basel)H-Index: 8
#2Dominik Witzigmann (University of Basel)H-Index: 16
Last. Jörg Huwyler (University of Basel)H-Index: 49
view all 4 authors...
The lack of efficient therapeutic options for many severe disorders including cancer spurs demand for improved drug delivery technologies. Nanoscale drug delivery systems based on poly(ethylene glycol)-poly(e-caprolactone) copolymers (PEG-PCL) represent a strategy to implement therapies with enhanced drug accumulation at the site of action and decreased off-target effects. In this review, we discuss state-of-the-art nanomedicines based on PEG-PCL that have been investigated in a preclinical sett...
152 CitationsSource
#1Philip Grossen (University of Basel)H-Index: 8
#2Gabriela Québatte (University of Basel)H-Index: 6
Last. Jörg Huwyler (University of Basel)H-Index: 49
view all 6 authors...
Nanoparticles are increasingly used to implement drug targeting strategies. In the present study, solid-sphere nanoparticles (SNPs) made of poly(ethylene glycol)-b-poly(ź-caprolactone) (PEG-b-PCL) were covalently linked to a monoclonal antibody (83-14źmAb) targeted against the human insulin receptor that is highly expressed on human brain microvascular endothelial cells. Resulting targeted SNPs were characterized using transmission electron microscopy (TEM), cryo-TEM, dynamic light scattering, a...
9 CitationsSource