Tuned Density of Anti-Tissue Factor Antibody Fragment onto siRNA-Loaded Polyion Complex Micelles for Optimizing Targetability into Pancreatic Cancer Cells

Biomacromolecules
Hyun Su MinKazunori Kataoka

Abstract

Antibody fragment (Fab')-installed polyion complex (PIC) micelles were constructed to improve targetability of small interfering RNA (siRNA) delivery to pancreatic cancer cells. To this end, we synthesized a block copolymer of azide-functionalized poly(ethylene glycol) and poly(l-lysine) and prepared PIC micelles with siRNA. Then, a dibenzylcyclooctyne (DBCO)-modified antihuman tissue factor (TF) Fab' was conjugated to azido groups on the micellar surface. A fluorescence correlation spectroscopic analysis revealed that 1, 2, or 3 molecule(s) of Fab'(s) were installed onto one micellar nanoparticle according to the feeding ratio of Fab' (or DBCO) to micelle (or azide). The resulting micelles exhibited ∼40 nm in hydrodynamic diameter, similar to that of the parent micelles before Fab' conjugation. Flow cytometric analysis showed that three molecules of Fab'-installed PIC micelles (3(Fab')-micelles) had the highest binding affinity to cultured pancreatic cancer BxPC3 cells, which are known to overexpress TF on their surface. The 3(Fab')-micelles also exhibited the most efficient gene silencing activity against polo-like kinase 1 mRNA in the cultured cancer cells. Furthermore, the 3(Fab')-micelles exhibited high penetrability and t...Continue Reading

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Citations

Jul 30, 2019·Advanced Materials·Peng MiKazunori Kataoka
Aug 31, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Xuhong ZhaoShengsong Tang
May 20, 2020·Therapeutic Advances in Medical Oncology·Tianqi SuJiannan Li
May 4, 2021·Chemical Reviews·Ramya KumarTheresa M Reineke
Jun 26, 2021·Biotechnology and Bioengineering·Shahin AghamiriHossein Ghanbarian
Oct 30, 2019·Biomacromolecules·Huanli SunChao Deng
Jun 12, 2018·Biomacromolecules·Huanli SunZhiyuan Zhong

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