Thermo‐Responsive Complexes of c‐Myc Antisense Oligonucleotide with Block Copolymer of Poly(OEGMA) and Quaternized Poly(4‐Vinylpyridine)

Abstract

Solution behavior of thermo-responsive polymers and their complexes with biological macromolecules may be affected by environmental conditions, such as the concentration of macromolecular components, pH, ion concentration, etc. Therefore, a thermo-responsive polymer and its complexes should be characterized in detail to observe their responses against possible environments under physiological conditions before biological applications. To briefly indicate this important issue, thermo-responsive block copolymer of quaternized poly(4-vinylpyridine) and poly(oligoethyleneglycol methyl ether methacrylate) as a potential nonviral vector has been synthesized. Polyelectrolyte complexes of this copolymer with the antisense oligonucleotide of c-Myc oncogene are also thermo-responsive but, have lower LCST (lower critical solution temperature) values compared to individual copolymer. LCST values of complexes decrease with molar ratio of macromolecular components and presence of salt. Dilution of solutions also affects solution behavior of complexes and causes a significant decrease in size and an increase in LCST, which indicates possible effects of severe dilutions in the blood stream.

Synthesis, Assembled Structures, and DNA Complexation of Thermoresponsive Lysine-Based Zwitterionic and Cationic Block Copolymers

“…Another segment in the block copolymer can contribute to improvement in the properties of the polyplexes, such as their solubility, stability, cell survival, and biodistribution, depending on the nature of the segment. Cationic block copolymers with stimuli-responsive segments have been studied as promising candidates for stimuli-responsive gene delivery vectors, in which DNA uptake and gene release ability can be manipulated by external stimuli. , Several block copolymers consisting of cationic and thermoresponsive segments have been developed, which include quaternized poly­(4-vinylpyridine)- b -poly­(oligoethyleneglycol methyl ether methacrylate), poly­(2-(dimethylamino)­ethyl acrylate)- b -poly­(NIPAM), poly­(ethyleneimine)- b -poly­(NIPAM), and poly­((3-acrylamidopropyl)­trimethylammonium chloride)- b -poly­(NIPAM). − Poly­(NIPAM)-based random copolymers with cationic species have also been investigated as stimuli-responsive gene delivery vectors . Other examples involve a triblock copolymer consisting of hydrophilic poly­(2-ethyl-2-oxazoline), thermoswitchable amphiphilic poly­(2- n -propyl-2-oxazoline), cationic poly­( l -lysine), and double thermoresponsive polybetaine-based ABA triblock copolymers .…”

Synthesis of doxorubicin‐loaded PBMA‐b‐POEGMA micelles and assessment of its anticancer activity against breast cancer cells (4T1)

“…Dilution is an important obstacle for drug delivery systems and nonviral vectors prepared by self‐assembly, because dilution may cause disassembly of these particles. Generally, it is known that the total blood volume of a man is approximately between 4.75 and 6.23 L 55,56 . When a 5 mL solution of a micelle is administered intravenously to the body, the solution can be diluted almost up to 1000 times.…”

Self-Assembly and Applications of Amphiphilic Hybrid POSS Copolymers

“…However, thermoresponsive polymers are completely soluble in the solvent in all proportions at temperatures below the lower critical solution temperature (LCST) and become insoluble above the LCST. The thermosensitive micelles mainly consist of N -isopropylacryl amide (NIPAM) [ 90 , 94 , 95 , 96 ], propylene glycol [ 67 , 97 ], ε-caprolactone [ 98 , 99 , 100 ], and oligo(ethylene glycol) methacrylate (OEGMA) [ 101 , 102 , 103 ].…”