Temperature- and pH-Responsive Self-assembly of Poly(propylene oxide)-b-Poly(lysine) Block Copolymers in Aqueous Solution

Abstract

A series of poly(propylene oxide)-b-poly(L-lysine) (PPO-PK) block copolymers were synthesized using Huisgen's 1,3-dipolar cycloaddition, and the solution self-assembly was studied using transmission electron microscopy, circular dichroism spectroscopy, and dynamic and static light scattering techniques. In contrast to previous studies of poly(lysine)-based block copolymers, PPO-PK exhibits a significant shift in the pH associated with the helix-coil transition of the poly(lysine) block, potentially a result of decreased hydrophobicity in the core PPO block. Given the proximity of the lower critical solution temperature of the PPO block, these materials exhibit both pH and temperature-responsive (i.e., "schizophrenic") self-assembly, the latter of which was interpreted in terms of changes in the second osmotic virial coefficient. Finally, the vesicle morphology obtained from these polymers was studied for the propensity in drug encapsulation and passive release.

Self‐assembly and responsiveness of polypeptide‐based block copolymers: How “Smart” behavior and topological complexity yield unique assembly in aqueous media

“…67 Similarly, our group recently reported temperature-responsive micelles and vesicles of poly(propylene oxide)-b-PLys (PPO-b-PLys) block copolymers (PPO LCST ¼ 10 C). 11 Through the use of dynamic light scattering, we observed a sharp increase in scattering intensity above the LCST denoting a unimer to micelle/vesicle transition. Furthermore, we illustrated the potential for schizophrenic behavior of these assemblies at low temperature and high pH (Fig.…”

“…[55][56][57] Assemblies with Polypeptide Coronas The past two decades have seen several literature reports of aqueous assembly of block copolymers with peptide corona chains, whereby responsiveness is governed in part by changes in the secondary structure. 11,42,[58][59][60][61][62][63][64][65][66][67][68][69][70][71][72] Much of this research focus has been devoted to pH-responsive block copolymers containing peptides such as poly(L-lysine) (PLys) (pKa 10.3) 73 and poly(L-glutamic acid) (PLGA) (pKa 4.3) 70 which exhibit helix-coil transitions associated with the charged state of the amino or carboxylic acid side chains of PLys and PGlu respectively.…”

“…11,62 By performing in-depth light scattering studies, we were able to calculate a hydrophobic core size based on the aggregation number (N agg ) determined from Zimm analysis, assuming a fully dehydrated core. A theoretical change in assembly dimensions can be estimated from the change in the rise/ repeat unit for the peptide as a result of the helix-coil transition (random coil ¼ 0.37 nm, a-helix ¼ 0.15 nm).…”

“…11 The theoretical sizes of vesicles and worm-like micelles are difficult to predict, yet the thickness of these types of assemblies is often dictated by the chain length of the hydrophobic blocks. 12 Other non-typical morphologies such as multi-compartment micelles, [13][14][15] disk micelles, [16][17][18][19] nanotubes, 20 toroidal micelles, 21,22 bicontinuous micelles, 23,24 and corkscrew micelles 25 have been observed, often arising through structural complexity, solvent composition, or specific interactions.…”

“…Pioneering research on pH and salt responsiveness involved synthetic polyelectrolytes such as poly(acrylic acid) and poly(vinyl pyridine) coupled to neutral, hydrophobic blocks (i.e., poly(butadiene)), where changes in pH or salt concentration impacted the ionic nature of the hydrophilic block. [36][37][38][39][40] Common examples of temperature responsiveness are a result of the incorporation of blocks that contain a lower critical solution temperature (LCST) such as poly(N-isopropyl acrylamide) 41 or poly(propylene oxide) 11 or the incorporation of polypeptides where the secondary structure transitions with temperature (i.e., a-helix to b-sheet). 42 Polypeptide-based block copolymers offer many advantages in the realm of responsive block copolymer self-assembly such as biocompatibility and enhanced biofunctionality.…”