Novel Temperature/Reduction Dual-Stimulus Responsive Triblock Copolymer [P(MEO2MA-co- OEGMA)-b-PLLA-SS-PLLA-b-P(MEO2MA-co-OEGMA)] via a Combination of ROP and ATRP: Synthesis, Characterization and Application of Self-Assembled Micelles

Abstract

Novel temperature/reduction dual stimulus-responsive triblock copolymers, poly [2-(2-methoxyethoxy) ethyl methacrylate-co-oligo (ethylene glycol) methacrylate]-b-(L-polylactic acid)-SS-b-(L-polylactic acid)-b-poly[2-(2-methoxyethoxy) ethyl methacrylate-co-oligo(ethylene glycol)methacrylate] [P(MEO2MA-co-OEGMA)-b-PLLA-SS-PLLA-b-P(MEO2MA-co-OEGMA)] (SPMO), were synthesized by ring opening polymerization (ROP) of L-lactide and 2,2’-dithio diethanol (SS-DOH), and random copolymerization of MEO2MA and OEGMA monomers via atom transfer radical polymerization (ATRP) technology. The chemical structures and compositions of the novel copolymers were demonstrated by proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FTIR). The molecular weights of the novel copolymers were measured by size exclusive chromatography (SEC) and proved to have a relatively narrow molecular weight distribution coefficient (ÐM ≤ 1.50). The water solubility and transmittance of the novel copolymers were tested via visual observation and UV–Vis spectroscopy, which proved the SPMO had a good hydrophilicity and suitable low critical solution temperature (LCST). The critical micelle concentration (CMC) of the novel polymeric micelles were determined using surface tension method and fluorescent probe technology. The particle size and morphology of the novel polymeric micelles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The sol–gel transition behavior of the novel copolymers was studied via vial flip experiments. Finally, the hydrophobic anticancer drug doxorubicin (DOX) was used to study the in vitro release behavior of the novel drug-loaded micelles. The results show that the novel polymeric micelles are expected to become a favorable drug carrier. In addition, they exhibit reductive responsiveness to the small molecule reducing agent dithiothreitol (DTT) and temperature responsiveness with temperature changes.

Synthesis approaches of amphiphilic copolymers for spherical micelle preparation: application in drug delivery

“…Therefore, higher temperature and larger amount of GSH in tumor cells can facilitate the DOX release, thereby providing higher cytotoxicity. 101 ROP and ATRP were used by Danfeng et al for the preparation of P(MEO 2 MA-co-OEGMA)-b-PCL-SS-PCL-b-P(MEO 2 MA-co-OEGMA), in which bis-(2-hydroxyethyl) disulfide was applied to initiate a ROP reaction to obtain PCL-SS-PCL. The resulting product was then reacted with BiBB to produce Br-PCL-SS-PCL-Br as the ATRP agent.…”

“…Therefore, higher temperature and larger amount of GSH in tumor cells can facilitate the DOX release, thereby providing higher cytotoxicity. 101…”

Combinations (Є) among controlled/living polymerizations and utilizations of efficient chemical reactions for the synthesis of novel polymeric materials

“…Numerous studies have reported work based on the simple ROP- Є -ATRP approach. 151–158 For example, poly(vinyl phenol) (PVPh) can lead to enhanced miscible blends with several polymers through the formation of intermolecular hydrogen bond interactions between the pendent phenol and ester, hydroxy, pyridine, and ether groups. However, phenol derivatives can act as an effective radical scavenger, resulting in non-polymerization of vinyl phenol through free radical polymerization.…”

Topology Reliable LCST‐Type Behavior of ABA Triblock Polymer and Influence on Water Condensation and Crystallization

“…Smart hydrogels have been much concerned due to the stimulus responsive behaviors to the environmental triggers. [ 1–4 ] In order to develop their potential applications in various fields, such as wearable electronic devices, [ 5–8 ] flexible sensors, [ 9–13 ] biological drug‐carrying, [ 14–18 ] and storage cells, [ 19–21 ] it is very significant to adjust their sol–gel transition temperature ( T gel ). Their special swelling behavior at certain lower or upper critical solution temperatures (LCST or UCST) has promoted the applications as anti‐fogging and anti‐icing materials through delaying the coalescence of condensed drops and inhibiting ice nucleation and/or growth, respectively.…”