TY  - JOUR
AB  - Multispecific antibodies have emerged as versatile therapeutic agents, and therefore, approaches to optimize and streamline their design and assembly are needed. Here we report on the modular and programmable assembly of IgG antibodies, F(ab) and scFv fragments on DNA origami nanocarriers. We screened 105 distinct quadruplet antibody variants in vitro for the ability to activate T cells in the presence of target cells. T-cell engagers were identified, which in vitro showed the specific and efficient T-cell-mediated lysis of five distinct target cell lines. We used these T-cell engagers to target and lyse tumour cells in vivo in a xenograft mouse tumour model. Our approach enables the rapid generation, screening and testing of bi- and multispecific antibodies to facilitate preclinical pharmaceutical development from in vitro discovery to in vivo proof of concept.
AU  - Wagenbauer, K.F.*
AU  - Pham, N.*
AU  - Gottschlich, A.*
AU  - Kick, B.*
AU  - Kozina, V.*
AU  - Frank, C.*
AU  - Trninic, D.*
AU  - Stömmer, P.*
AU  - Grünmeier, R.*
AU  - Carlini, E.*
AU  - Tsiverioti, C.A.*
AU  - Kobold, S.
AU  - Funke, J.J.*
AU  - Dietz, H.*
C1  - 67990
C2  - 54468
CY  - Heidelberger Platz 3, Berlin, 14197, Germany
SP  - 1319-1326
TI  - Programmable multispecific DNA-origami-based T-cell engagers.
JO  - Nat. Nanotechnol.
VL  - 18
IS  - 11
PB  - Nature Portfolio
PY  - 2023
SN  - 1748-3387
ER  - 

TY  - JOUR
AB  - The design of cancer-targeting particles with precisely tuned physicochemical properties may enhance the delivery of therapeutics and access to pharmacological targets. However, a molecular-level understanding of the interactions driving the fate of nanomedicine in biological systems remains elusive. Here, we show that ultrasmall (<10 nm in diameter) poly(ethylene glycol)-coated silica nanoparticles, functionalized with melanoma-targeting peptides, can induce a form of programmed cell death known as ferroptosis in starved cancer cells and cancer-bearing mice. Tumour xenografts in mice intravenously injected with nanoparticles using a high-dose multiple injection scheme exhibit reduced growth or regression, in a manner that is reversed by the pharmacological inhibitor of ferroptosis, liproxstatin-1. These data demonstrate that ferroptosis can be targeted by ultrasmall silica nanoparticles and may have therapeutic potential.
AU  - Kim, S.E.*
AU  - Zhang, L.*
AU  - Ma, K.*
AU  - Riegman, M.*
AU  - Chen, F.*
AU  - Ingold, I.
AU  - Conrad, M.
AU  - Turker, M.Z.*
AU  - Gao, M.*
AU  - Jiang, X.*
AU  - Monette, S.*
AU  - Pauliah, M.*
AU  - Gonen, M.*
AU  - Zanzonico, P.*
AU  - Quinn, T.*
AU  - Wiesner, U.*
AU  - Bradbury, M.S.*
AU  - Overholtzer, M.*
C1  - 49561
C2  - 40793
SP  - 977-985
TI  - Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth.
JO  - Nat. Nanotechnol.
VL  - 11
PY  - 2016
SN  - 1748-3387
ER  - 

TY  - JOUR
AB  - Inorganic nanoparticles are frequently engineered with an organic surface coating to improve their physicochemical properties, and it is well known that their colloidal properties may change upon internalization by cells. While the stability of such nanoparticles is typically assayed in simple in vitro tests, their stability in a mammalian organism remains unknown. Here, we show that firmly grafted polymer shells around gold nanoparticles may degrade when injected into rats. We synthesized monodisperse radioactively labelled gold nanoparticles ((198)Au) and engineered an (111)In-labelled polymer shell around them. Upon intravenous injection into rats, quantitative biodistribution analyses performed independently for (198)Au and (111)In showed partial removal of the polymer shell in vivo. While (198)Au accumulates mostly in the liver, part of the (111)In shows a non-particulate biodistribution similar to intravenous injection of chelated (111)In. Further in vitro studies suggest that degradation of the polymer shell is caused by proteolytic enzymes in the liver. Our results show that even nanoparticles with high colloidal stability can change their physicochemical properties in vivo.
AU  - Kreyling, W.G.
AU  - Abdelmonem, A.M.*
AU  - Ali, Z.*
AU  - Alves, F.*
AU  - Geiser, M.*
AU  - Haberl, N.
AU  - Hartmann, R.*
AU  - Hirn, S.
AU  - de Aberasturi, D.J.*
AU  - Kantner, K.*
AU  - Khadem-Saba, G.
AU  - Montenegro, J.M.*
AU  - Rejman, J.*
AU  - Rojo, T.*
AU  - de Larramendi, I.R.*
AU  - Ufartes, R.*
AU  - Wenk, A.
AU  - Parak, W.J.*
C1  - 45243
C2  - 37275
CY  - London
SP  - 619-623
TI  - In vivo integrity of polymer-coated gold nanoparticles.
JO  - Nat. Nanotechnol.
VL  - 10
IS  - 7
PB  - Nature Publishing Group
PY  - 2015
SN  - 1748-3387
ER  -