Tuning of Thermoresponsivity of a Poly(2‐alkyl‐2‐oxazoline) Block Copolymer by Interaction with Surface‐Active and Chaotropic Metallacarborane Anion

Abstract

Thermoresponsive nanoparticles based on the interaction of metallacarboranes, bulky chaotropic and surface-active anions, and poly(2-alkyl-2-oxazoline) block copolymers were prepared. Recently, the great potential of metallacarboranes have been recognized in biomedicine and many delivery nanosystems have been proposed. However, none of them are thermoresponsive. Therefore, a thermoresponsive block copolymer, poly(2-methyl-2-oxazoline)-block-poly(2-n-propyl-2-oxazoline) (PMeOx-PPrOx), was synthesized to encapsulate metallacarboranes. Light scattering, NMR spectroscopy, isothermal titration calorimetry, and cryogenic TEM were used to characterize all solutions of the formed nanoparticles. The cloud-point temperature (T ) of the block copolymer was observed at 30 °C and polymeric micelles formed above this temperature. Cobalt bis(dicarbollide) anion (COSAN) interacts with both polymeric segments. Depending on the COSAN concentration, this affinity influenced the phase transition of the thermoresponsive PPrOx block. The T shifted to lower values at a lower COSAN content. At higher COSAN concentrations, the hybrid nanoparticles are fragmented into relatively small pieces. This system is also thermoresponsive, whereby an increase in temperature leads to higher polymer mobility and COSAN release.

The Chaotropic Effect as an Assembly Motif in Chemistry

“…40 The behavior of POMs has also been related to their superchaotropic character 16, 18. The intrinsic self‐assembly tendency of both superchaotropic anions (borate clusters and POMs) accounts also for their high propensity to accumulate at the water–air surface; this leads to surfactant‐like behavior, such as a reduction of the surface tension 11, 40, 53, 190, 191. Accordingly, because they lack the polar head group/hydrophobic tail design of classical amphiphiles, they have also been classified as non‐classical surfactants or “intrinsic amphiphiles” 11, 40, 53, 190, 191…”

“…Indeed, the previously determined thermochemical signature in the solid‐phase binding of dodecaborate cluster anions (enthalpically driven binding with large entropic penalty) fully agrees with this new interpretation. Moreover, in two independent lines of investigation, Matějíček and co‐workers have established the operation of the chaotropic effect for boron cluster anions, while the group of Bauduin and Diat have expanded the observed self‐assembly and surface‐assembly tendencies to POMs as superchaotropic anions …”

Effect of Dexamethasone on Thermoresponsive Behavior of Poly(2-Oxazoline) Diblock Copolymers

“…This finding has an implication for the development of thermoresponsive polymeric drug carriers, where T cp of the copolymer is precisely matched to the human body temperature, but the effect of the added drug is usually not considered. As an opposite example, Uchman et al [ 49 ] studied the effect of encapsulated metallacarborane cobalt bis(dicarbollide) anion (COSAN), potentially applicable in cancer and AIDS treatment, on thermoresponsive behavior of similar diblock copolymer P n PrOx 80 -PMeOx 40 . Similarly to our results, the authors described the shift of T cp of the system to lower values upon the addition of lower amounts of COSAN.…”

Preparing (Metalla)carboranes for Nanomedicine

“…The choice of a thermoresponsive block polymer system, for example, poly(2-methyl-2-oxazoline)block-poly(2-n-propyl-2-oxazoline) (PMeOx-PPrOx), allows the use of a physical external trigger to release the loading (here COSAN). [115] In all the studies, cations have a crucial role, which was elucidated in a study from 2016 by Matějíček and co-workers, who prepared a double-hydrophilic block copolymer, poly(ethylene oxide)block-poly(2-alkyloxazoline) (PEO-POX), assembled together with COSAN, which forms BÀ H•••HÀ C dihydrogen interactions leading to compact nanomaterials (star-like [PEO-POX] 4 /M-[COSAN] in 3 M solution of MCl, with M = Na + , Li + , and K + ). The counterions (Li + , Na + and K + ) drive the affinity of the binding of COSAN to either of the two block copolymers, and thus, determine the compartmentalisation.…”