Mixed Polyplex Micelles with Thermoresponsive and Lysine-Based Zwitterionic Shells Derived from Two Poly(vinyl amine)-Based Block Copolymers.
Ryosuke KantoRyo YonenumaMizuki YamamotoHiroyuki FurusawaShigekazu YanoMitsuru HarukiHideharu MoriPublished in: Langmuir : the ACS journal of surfaces and colloids (2021)
Two series of poly(vinyl amine) (PVAm)-based block copolymers with zwitterionic and thermoresponsive segments were synthesized by the reversible addition-fragmentation chain transfer polymerization. A mixture of the two copolymers, poly(N-acryloyl-l-lysine) (PALysOH) and poly(N-isopropylacrylamide) (PNIPAM), which have the same cationic PVAm chain but different shell-forming segments, were used to prepare mixed polyplex micelles with DNA. Both PVAm-b-PALysOH and PVAm-b-PNIPAM showed low cytotoxicity, with characteristic assembled structures and stimuli-responsive properties. The cationic PVAm segment in both block copolymers showed site-specific interactions with DNA, which were evaluated by dynamic light scattering, zeta potential, circular dichroism, agarose gel electrophoresis, atomic force microscopy, and transmission electron microscopy measurements. The PVAm-b-PNIPAM/DNA polyplexes showed the characteristic temperature-induced formation of assembled structures in which the polyplex size, surface charge, chiroptical property of DNA, and polymer-DNA binding were governed by the nitrogen/phosphate (N/P) ratio. The DNA binding strength and colloidal stability of the PVAm-b-PALysOH/DNA polyplexes could be tuned by introducing an appropriate amount of zwitterionic PALysOH functionality, while maintaining the polyplex size, surface charge, and chiroptical property, regardless of the N/P ratio. The mixed polyplex micelles showed temperature-induced stability originating from the hydrophobic (dehydrated) PNIPAM chains upon heating, and remarkable stability under salty conditions owing to the presence of the zwitterionic PALysOH chain on the polyplex surface.
Keyphrases
- dna binding
- circulating tumor
- single molecule
- cell free
- atomic force microscopy
- drug delivery
- cancer therapy
- transcription factor
- drug release
- nucleic acid
- hyaluronic acid
- high resolution
- circulating tumor cells
- endothelial cells
- climate change
- drug induced
- oxidative stress
- mass spectrometry
- solar cells
- oxide nanoparticles