The Design of Sulfobetaine Polymers with Thermoresponsiveness under Physiological Salt Conditions

Abstract

Thermoresponsive polymers are attractive in terms of basics and applications because of the phase separation in aqueous solution. Some sulfobetaine polymers are known for their antifouling biocompatibility and upper critical solution temperature (UCST) type thermoresponsiveness; however, thermoresponsiveness disappears in aliphatic sulfobetaine polymers in physiological salt conditions. Aromatic cation‐containing sulfobetaine polymers are not responded because of the strong intermolecular interactions. In this study, new sulfobetaine methacrylamides with a pyridinium cation, 3‐(4‐(2‐methacrylamido)alkyl pyridinio‐1‐yl)propane‐1‐sulfonates, (PySMAAm)s, are designed and then prepared the homopolymers using aqueous reversible addition‐fragmentation chain transfer polymerization. The P(PySMAAm)s exhibited UCST‐type thermoresponsiveness that is induced by substitution of the dipole–dipole interaction between the interpolymer side chain to an ion–dipole interaction in physiological salt conditions. The thermoresponsiveness is affected by the molecular weight and structure of the side chains. Such sulfobetaine polymers can be promising tools as biomaterials especially for drug delivery and regenerative medicine.

Control of Mitochondrial Localization Using Thermoresponsive Sulfobetaine Polymer

“…We reported that the CP of P(E‐PySMAAm) solutions was affected by a molecular weight less than 30 kDa in PBS. [ 37 ] Although P(E‐PySMAAm)33k exhibited a UCST‐like CP at 25.4 °C with a sharp transition behavior, P(E‐PySMAAm)14k showed no CP in PBS. Dynamic light scattering (DLS) measurements of P(E‐PySMAAm)33k indicated that the polymer form a micrometer‐sized aggregates below the CP, a nanometer‐sized (≈10 nm) distribution which might be attributed as the single chains above the CP, and the two distributions around the CP (Figure S1, Supporting Information).…”

“…P(E‐PySMAAm)s (14k: M n = 13 900 g mol −1 , M w / M n = 1.26; 33k: M n = 33 400, M w / M n = 1.34), P(M‐PySMAAm)14k ( M n = 14 300 g mol −1 , M w / M n = 1.78), and P(M‐PySMA)16k ( M n = 16 300 g mol −1 , M w / M n = 1.83) were prepared in the previous study. [ 37 ] Doxorubicin hydrochloride were purchased from Tokyo Chemical Industry (Tokyo, Japan). In addition, 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium chloride (DMT‐MM) was purchased from Wako Pure Chemical Industries (Tokyo, Japan).…”

“…The polymers were designed to substitute the zwitter ionic pair in the distal position from the main chain to provide thermoresponsiveness under physiological conditions. [ 37 ] P(PySMAAm)s exhibit UCST‐like thermoresponsiveness by adjusting the molecular weight and the alkyl chain length in the side chain. In this study, sulfobetaine polymers with pyridinium cations ( Figure 1 ) were added to cells, and internalization and localization were analyzed for further applications as thermoresponsive and mitochondrial selective nanocarriers.…”

Synthesis of Temperature‐Responsive Polymers Containing Piperidine Carboxamide and N,N‐diethylcarbamoly Piperidine Moiety via RAFT Polymerization

“…[ 4,5 ] The UCST‐type phase transition is driven by electrostatic or hydrogen bonding interactions, or both, among polymer chains. [ 5,6 ] To date, many LCST‐type temperature‐responsive polymers have been reported. [ 1,4,7–12 ] Among these, poly( N ‐isopropylacrylamide) (PIPAAm), in which LCST‐related phase transition occurs at 32 °C in water, is used in many biomedical applications, such as cell culturing, biomolecular separation, and drug delivery, because the LCST of PIPAAm is close to regular human body temperature.…”

“…Living radical polymerization techniques, such as atom transfer radical polymerization (ATRP) [ 23 ] and reversible addition‐fragmentation chain‐transfer (RAFT) polymerization, [ 24 ] have been exploited for the synthesis of UCST‐type polymers with controlled molecular weights and narrow molecular weight distributions. [ 6,25–28 ] RAFT polymerization also introduces the desired terminal groups of resultant polymers, depending on chain transfer agent (CTA) and initiator reagent. Poly( N ‐acryloyl‐glycineamide) (PNAGAm) have been studied as nonionic UCST‐type polymers.…”