Solution Conformation of Polymer Brushes Determines Their Interactions with DNA and Transfection Efficiency

Abstract

Polymer brush-functionalized nanomaterials offer interesting features for the design of gene delivery vectors as their physicochemical and structural properties can be designed independently of the chemistry, size and shape of the nanomaterial core. However, little is known of the parameters regulating the adsorption and infiltration of DNA molecules at the surface of positively charged polymer brushes, despite the importance of such processes for gene delivery. Here we investigate the role of the molecular environment (e.g., pH, type of buffer, concentration) on the interactions between plasmid DNA and positively charged poly(dimethylaminoethyl methacrylate) (PDMAEMA) brushes using a combination of light scattering, electrophoretic light scattering, in situ ellipsometry, and surface plasmon resonance. We show that the conformation of swollen PDMAEMA brushes is modulated by the surrounding buffer and that this impacts strongly on the ability of such brushes and nanomaterials based on these coatings to complex DNA molecules. In turn, the levels of transfection efficiency measured correlate with changes in brush conformation and DNA binding. Therefore, this work demonstrates the importance of molecular design of polymer brushes to control DNA complexation and release in order to optimize the performance of polymer brush-functionalized nanomaterials for gene delivery applications.

Conformational Dynamics and Responsiveness of Weak and Strong Polyelectrolyte Brushes: Atomistic Simulations of Poly(dimethyl aminoethyl methacrylate) and Poly(2-(methacryloyloxy)ethyl trimethylammonium chloride)

“…12 Recently, the high grafting density of positively charged polymer brushes has been shown to enable the highstability binding of oligonucleotides, making these brushes quite promising for gene and small RNA (siRNA and miRNA) delivery. 13,14 Cationic polymer brushes such as poly(dimethyl aminoethyl methacrylate) (PDMAEMA) have shown the potential to capture oligonucleotides, in particular small RNAs relevant for siRNA and miRNA delivery. 14 It was further observed that RNA interactions, specifically with oligonucleotides ranging in size between 20 and 30 base pairs, are more stable than corresponding DNA molecules of similar sizes.…”

Responsive Polymer Brush Design and Emerging Applications for Nanotheranostics

“…Tethering a chloro-and alkoxy-silane functionalized initiators to an oxidized silicon sub-strate is the most frequently applied route for the generation of polymer brushes via SI-CRP. This strategy is routinely used for the functionalization of a wide range of surfaces, including glass, quartz, [34] porous, [19,35] and nonporous silica particles, [18,36] as well as other nanoparticles displaying a silica shell (e.g., Fe 3 O 4 /silica nanoparticles [37] ). Noncovalent adsorption of polyelectrolyte macroinitiators (e.g., cationic trimethylammoniumbased macroinitiator and anionic sulfate-based macroinitiator) has also demonstrated the capability of modification of silicon oxide surfaces and efficient initiation polymerization.…”

“…For example, PDMAEMA with pendant tertiary amines is a temperature-and pH-responsive polymer, often used as cationic antibacterial surfaces and nonviral gene carriers for biomedical applications. [18,36,94,95] Many other responsive polymer brushes have been developed for use in drug delivery. We have summarized recent advances toward these applications in Table 1.…”

“…Rh6G dye Temperature P(OEGMA-co-MEO2MA) SWCNTs [96] Rh6G dye Temperature PNIPAAm-co-PAAm Au nanocage [97] Rh6G dye pH PDMAEMA MSNs [98] RhB dye pH PDEAEMA MSNs [99] Dye (Calcein) pH P4VP MSNs [ 100] Diol derivatives Saccharide and temperature PNIPAAm-co-PMAA AuNSs [ Doxorubicin, lysozyme Temperature PNIPAAm-co-PAAm Au nanocage [ 116] plasmid DNA pH and temperature PDMAEMA SPIONs [ 117] plasmid DNA pH PDMAEMA SPIONs [ 118] CPT, plasmid DNA pH PDMAEMA GO [ 119] plasmid DNA pH PDMAEMA LDHs [ 120] plasmid DNA pH PDMAEMA Chiral Si nanorods [ 121] plasmid DNA Shielding effect PDMAEMA Spindly CNCs [ 122] siRNA Bioreductivity Poly(DAMA-HEMA) Gold NPs [40] plasmid DNA pH PDMAEMA Silica NPs [36] plasmid DNA, siRNA pH PDMAEMA Silica NPs [95] siRNA pH PDMAEMA Silica NPs [18] siRNA pH PDMAEMA Silica NPs [39] plasmid DNA pH PDMAEMA Nanodiamond (with bioimaging) [ 123] siRNA pH PDMAEMA UCNPs (with phototherapy) [ 124] siPD-L1 Redox SPDP Magnetic nanoparticle (MRI imaging) [ 125] siPD-L1 Redox FA-PEG-SS-PEI SPION (MRI imaging) Applications of responsive polymer brushes for triggered drug delivery. A) PDEAEMA-coated silica nanoparticles and pH-sensitive controlled release of a model dye.…”

Simulações Computacionais Do Polímero Metacrilato De Dimetilaminoetila (Pdmaema) Para Carreamento De Ácidos Nucléicos

“…A adsorção de RNA com comprimento entre 20 and 30 bases é mais estável do que observado para moléculas de DNA de dimensões similares. 2,3 As bases moleculares desta preferência não são conhecidas. O presente trabalho tem como objetivo investigar estes processos.…”