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Reversible Protection and Targeted Delivery of DNA Origami with a Disulfide-Containing Cationic Polymer.
Youssef, Sarah; Tsang, Emily; Samanta, Anirban; Kumar, Vipin; Gothelf, Kurt V.
Afiliação
  • Youssef S; Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, 8000, Denmark.
  • Tsang E; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt.
  • Samanta A; Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, 8000, Denmark.
  • Kumar V; Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, 8000, Denmark.
  • Gothelf KV; Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, 8000, Denmark.
Small ; 20(10): e2301058, 2024 Mar.
Article em En | MEDLINE | ID: mdl-37916910
DNA nanostructures have considerable biomedical potential as intracellular delivery vehicles as they are highly homogeneous and can be functionalized with high spatial resolution. However, challenges like instability under physiological conditions, limited cellular uptake, and lysosomal degradation limit their use. This paper presents a bio-reducible, cationic polymer poly(cystaminebisacrylamide-1,6-diaminohexane) (PCD) as a reversible DNA origami protector. PCD displays a stronger DNA affinity than other cationic polymers. DNA nanostructures with PCD protection are shielded from low salt conditions and DNase I degradation and show a 40-fold increase in cell-association when linked to targeting antibodies. Confocal microscopy reveals a potential secondary cell uptake mechanism, directly delivering the nanostructures to the cytoplasm. Additionally, PCD can be removed by cleaving its backbone disulfides using the intracellular reductant, glutathione. Finally, the application of these constructs is demonstrated for targeted delivery of a cytotoxic agent to cancer cells, which efficiently decreases their viability. The PCD protective agent that is reported here is a simple and efficient method for the stabilization of DNA origami structures. With the ability to deprotect the DNA nanostructures upon entry of the intracellular space, the possibility for the use of DNA origami in pharmaceutical applications is enhanced.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polímeros / Nanoestruturas Idioma: En Revista: Small Assunto da revista: ENGENHARIA BIOMEDICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Dinamarca País de publicação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polímeros / Nanoestruturas Idioma: En Revista: Small Assunto da revista: ENGENHARIA BIOMEDICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Dinamarca País de publicação: Alemanha