Synthesis and characterization of variable conformation pH responsive block co-polymers for nucleic acid delivery and targeted cell entry

Abstract

Responsive materials that change conformation with varying pH have been prepared from a range of amphiphilic block co-polymers. The individual blocks are composed of (a) permanently hydrophilic chains with neutral functionality and (b) acrylate polymers with weakly basic side-chains. Variation in co-monomer content, molar mass and block ratios/compositions leads to a range of pH-responses, manifest through reversible self-assembly into micelles and/or polymersomes. These transitions can be tuned to achieve environmental responses in a pH range from 5–7, as shown by turbidimetric analysis, NMR and dynamic light scattering measurements (DLS). Further characterization by transmission electron microscopy (TEM) indicates that polymersomes with diameters of 100–200 nm can be formed under certain pH-ranges where the weakly basic side-chains are deprotonated. The ability of the systems assembled with these polymers to act as pH-responsive containers is shown by DNA encapsulation and release studies, and their potential for application as vehicle for drug delivery is proved by cell metabolic activity and cell uptake measurements

Enhanced Selective Sonosensitizing Efficacy of Ultrasound-Based Anticancer Treatment By Targeted Gold Nanoparticles

“…Folate-PEG 3.5kDa -SH (FA-PEG-SH) conjugate was synthesised according to the method reported in the literature [30] (Scheme I). Conjugate was purified from unreacted NHS-folate by gel filtration and then treated with TCEP to reduce the oxidized diemeric species (FA-PEG-S-S-PEG-FA).…”

Polymeric 3D nano-architectures for transport and delivery of therapeutically relevant biomacromolecules

“…In a related study, tumour microenvironments characterised by an acidic nature were addressed by pH sensitive polymersomes of di-or triblock copolymers consisting of PEG, poly(imidazole-butyl) methacrylate and poly(glycidylmethacrylate) blocks. 91 Double stranded DNA was encapsulated in these vesicles and release of their payloads occurred only under specific pH conditions. Non-viral vectors based on polymersomes have been shown to act as efficient nanocarriers in vitro, but most of these systems do not live up to the expectations to accomplish their task in vivo.…”

“…Carrier architectures siRNA dendrimer, 24,40,41,159 micelle, [74][75][76] polymeric vesicle, 87 multicompartment micelle, 142 polyplex nanoparticle 8,44,152,156 DNA dendrimer, 30,32,33,42,43,45,51,52,55 polymeric vesicle, 91,100 peptidic vesicle, 131 peptidic nanoparticle, [143][144][145]147,148…”

Nanostructural Systems Developed with Positive Charge Generation to Drug Delivery

“…The pH‐responsive feature of His‐containing materials can also be used for gene drug delivery . A small interfering RNA (siRNA)‐loaded polyelectrolyte has been constructed with branched polyethylenimine (bPEI) and copolymers, consisting of PEG, His, and glutamic acid (Glu) .…”