Control of aggregation temperatures in mixed and blended cytocompatible thermoresponsive block co-polymer nanoparticles

Abstract

A small library of thermoresponsive amphiphilic copolymers based on polylactide-block-poly((2-(2-methoxyethoxy)ethyl methacrylate)-co-(oligoethylene glycol methacrylate)) (PLA-b-P(DEGMA)-co-(OEGMA)), was synthesised by copper-mediated controlled radical polymerisation (CRP) with increasing ratios of OEGMA : DEGMA. These polymers were combined in two ways to form nanoparticles with controllable thermal transition temperatures as measured by particle aggregation. The first technique involved the blending of two (PLA-b-P(DEGMA)-co-(OEGMA)) polymers together prior to assembling nanoparticles (NPs). The second method involved mixing pre-formed nanoparticles of single (PLA-b-P(DEGMA)-co-(OEGMA)) polymers. The observed critical aggregation temperature T did not change in a linear relationship with the ratios of each copolymer either in the nanoparticles blended from different copolymers or in the mixtures of pre-formed nanoparticles. However, where co-polymer mixtures were based on (OEG)MA ratios within 5-10 mole%, a linear relationship between (OEG)MA composition in the blends and T was obtained. The data suggest that OEGMA-based copolymers are tunable over a wide temperature range given suitable co-monomer content in the linear polymers or nanoparticles. Moreover, the thermal transitions of the nanoparticles were reversible and repeatable, with the cloud point curves being essentially invariant across at least three heating and cooling cycles, and a selected nanoparticle formulation was found to be readily endocytosed in representative cancer cells and fibroblasts.

Switching of Macromolecular Ligand Display by Thermoresponsive Polymers Mediates Endocytosis of Multiconjugate Nanoparticles

“…Investigations of nanoparticle endocytosis were conducted in HeLa cells in accord with previous protocols. , Conditions of low particle concentration were chosen to minimize self-association of nanoparticles at temperatures above which the pPEGMA chains were expected to undergo coil-to-globule transitions, as this has been a confounding factor in prior responsive particle endocytosis experiments, , but this constraint meant that the assays were close to the limits of accurate quantitation of nanoparticle uptake. We also worked in low protein media (DMEM + 0.1% BSA) to reduce the potential for protein corona formation.…”

Multi-stimuli-responsive copolymers based on 1-pyrenol polyphotoacids

“…12,13 For example, Alexander and co-workers achieved several transition temperatures for polylactide-blockpoly((2-(2-methoxyethoxy)ethyl methacrylate)-co-(oligoethylene glycol methacrylate)) (OEG 2 MA and OEG 9 MA, respectively) not only by varying the ratio of OEGMA units, but also in mixed solutions of pre-formed nanoparticles. 14 In another study, a series of random copolymers with transition temperatures in the range from 21.5 °C to 66.5 °C was obtained by the copolymerization of OEG 5 MA and hydroxyethylmethacrylate (HEMA). 15 Recent studies have focussed on the development of multistimuli-responsive materials combining different triggers to achieve versatile control of the materials' properties, e.g.…”