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

Tuned Density of Anti-Tissue Factor Antibody Fragment onto siRNA-loaded Polyion Complex Micelle for Optimizing Targetability into Pancreatic Cancer Cells. Biomacromolecules. 2018 May 16;: Authors: Min HS, Kim HJ, Ahn J, Naito M, Hayashi K, Toh K, Kim BS, Matsumura Y, Kwon IC, Miyata K, Kataoka K 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) (PEG) and poly(L-lysine) (PLL), and prepared PIC micelles with siRNA. Then, a dibenzylcyclooctyne (DBCO)-modified anti-human tissue factor (TF) Fab' was conjugated to azido groups on the micellar surface. A fluorescence correlation spectroscopic (FCS) 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 approximately 40 nm in hydrodynamic diameter, similar to that of the parent micelle before Fab' conjugation. A flow cytometric analysis showed that three molecules of Fab'-installed PIC micelle (3(Fab')-micelle) had the highest binding affinity to cultured pancreatic cancer BxPC3 cells, which are known to overexpress TF on their surface. The 3(Fab')-micelle also exhibited the most efficient gene silencing activity aga...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research