Order–Order Morphological Transitions for Dual Stimulus Responsive Diblock Copolymer Vesicles

Abstract

A series of non-ionic poly(glycerol monomethacrylate)–poly(2-hydroxypropyl methacrylate) (PGMA–PHPMA) diblock copolymer vesicles has been prepared by reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of HPMA at 70 °C at low pH using a carboxylic acid-based chain transfer agent. The degree of polymerization (DP) of the PGMA block was fixed at 43, and the DP of the PHPMA block was systematically varied from 175 to 250 in order to target vesicle phase space. Based on our recent work describing the analogous PGMA–PHPMA diblock copolymer worms [LovettJ. R.LovettJ. R.25418214Angew. Chem.20155412791283], such diblock copolymer vesicles were expected to undergo an order–order morphological transition via ionization of the carboxylic acid end-group on switching the solution pH. Indeed, irreversible vesicle-to-sphere and vesicle-to-worm transitions were observed for PHPMA DPs of 175 and 200, respectively, as judged by turbidimetry, transmission electron microscopy (TEM), and dynamic light scattering (DLS) studies. However, such morphological transitions are surprisingly slow, with relatively long time scales (hours) being required at 20 °C. Moreover, no order–order morphological transitions were observed for vesicles comprising longer membrane-forming blocks (e.g., PGMA43–PHPMA225–250) on raising the pH from pH 3.5 to pH 6.0. However, in such cases the application of a dual stimulus comprising the same pH switch immediately followed by cooling from 20 to 5 °C, induces an irreversible vesicle-to-sphere transition. Finally, TEM and DLS studies conducted in the presence of 100 mM KCl demonstrated that the pH-responsive behavior arising from end-group ionization could be suppressed in the presence of added electrolyte. This is because charge screening suppresses the subtle change in the packing parameter required to drive the morphological transition.

New Insights into RAFT Dispersion Polymerization‐Induced Self‐Assembly: From Monomer Library, Morphological Control, and Stability to Driving Forces

“…Variable‐temperature 1 H NMR analysis revealed that the degree of hydration of the PHPMA block varied with temperature, leading to a subtle alteration in the packing parameter and thus a morphological transition between worms and spheres. Later, a pH‐responsive mechanism based on ionization of a single end‐group, such as carboxylic acid or morpholine, to change the morphologies was reported. Ionization of a polymer end‐group with a minimum use of base or acid induced a sufficient change in the hydration degree of the PHPMA block and thus the packing parameter, leading to a pH‐responsive morphological transition.…”

“…Ionization of a polymer end‐group with a minimum use of base or acid induced a sufficient change in the hydration degree of the PHPMA block and thus the packing parameter, leading to a pH‐responsive morphological transition. On the basis of the primary thermally responsive behavior of PHPMA‐based nano‐objects, PGMA−PHPMA vesicles with pH‐responsive end‐groups were reported to exhibit complex stimulus‐responsive behavior, which critically depended on PHPMA DP, pH, and temperature …”

Reactive and Functional Nanoobjects by Polymerization‐Induced Self‐Assembly

“…Using 3‐aminophenylboronic acid as binding agent to the pendent cis ‐diol groups of PGMA allowed the phase transition of vesicles with thicker walls to worms at specific DP n,PHPMA . Compared with the end group–driven phase transition of similar nanoobjects described above, that is, HOOC‐PGMA‐ b ‐PHPMA, lateral‐group functionalization showed a higher transition rate and efficiency. The in situ release of encapsulated silica NPs with 20 nm of diameter through vesicle dissociation was also demonstrated at a controlled rate by varying the solution pH and/or 3‐aminophenylboronic acid concentration.…”

“…Lovett et al. presented the synthesis of poly(glycerol monomethacrylate)‐ block ‐poly(2‐hydroxylpropyl methacrylate) (PGMA‐ b ‐PHPMA) diblock copolymer vesicles by aqueous RAFTPISA ( Scheme ) using carboxylic acid–functionalized RAFT agent 4 (Scheme ) . With a PGMA of low degree of polymerization ( DP n,PGMA = 43), vesicles can be obtained with DP n,PHPMA = 175, 200, 225, and 250.…”

“…End‐group ionization‐induced morphological transformations of vesicles b) obtained by RAFTPISA a). Reproduced with permission . Copyright 2016, American Chemical Society.…”