Bottom-Up Evolution of Vesicles from Disks to High-Genus Polymersomes

Abstract

SummaryPolymersomes are vesicles formed by the self-assembly of amphiphilic copolymers in water. They represent one of the most promising alternatives of natural vesicles as they add new possibilities in the amphiphiles' molecular engineering of aqueous compartments. Here we report the design of polymersomes using a bottom-up approach wherein self-assembly of amphiphilic copolymers poly(2-(methacryloyloxy) ethyl phosphorylcholine)-poly(2-(diisopropylamino) ethyl methacrylate) (PMPC-PDPA) into membranes is tuned using pH and temperature. We report evolution from disk micelles, to vesicles, to high-genus vesicles (vesicles with many holes), where each passage is controlled by pH switch or temperature. We show that the process can be rationalized, adapting membrane physics theories to disclose scaling principles that allow the estimation of minimal radius of vesiculation as well as chain entanglement and coupling. This approach allows us to generate nanoscale vesicles with genus from 0 to 70, which have been very elusive and difficult to control so far.

Combinatorial entropy behaviour leads to range selective binding in ligand-receptor interactions

“…Poly(ethylene glycol)-block-poly(2-(diisopropyl amino) ethyl methacrylate) (PEG-b-PDPA) and N 3 -PEG-b-PDPA copolymers were synthesised as previously reported by the atom-transfer radical polymerisation method 40 , 41 . For the fluorescent-labelling (Cy 5 -PEG 113 -PDPA 100 ) and ligand-conjugation (Angiopep 2 -PEG 68 -PDPA 90 ) one eq of N 3 -PEG-b-PDPA was first assembled in phosphate-buffered saline (PBS) by pH switch procedure 42 . The solution of self-assembled polymer was then degassed by sonication and inert gas flow under stirring.…”

Molecular bionics – engineering biomaterials at the molecular level using biological principles

“…When the CMC is high, as it happens for small amphiphiles such as surfactant molecules, there is a rapid exchange of amphiphiles molecules (i.e., unimers) between the assembly and the pool of free unimers, which leads to stable assemblies in thermodynamic equilibrium. Larger amphiphiles such as block copolymer molecules, have virtually zero CMC, leading to kinetically-trapped assemblies which do not exchange unimers with the external environment [44]. The exchange of unimers with the external environment may result in destabilization of the assemblies, for example, if the unimers in solution are degraded by an enzyme and therefore, removed.…”

“…As mentioned above, amphiphile membranes and vesicles are essential to life because they allow compartmentalization of cells and other organelles inside them. The formation of a vesicle can be explained as if a bilayer disk was closed as a pulled bag, enclosing a volume of water, which involves a balance between the energy needed to bend the disk and the energy arising from the line tension associated with the rim of the bilayer disk [44]. Vesicle formation arises when the bending elasticity is low and the surface tension high.…”

“…Many examples of kinetically-trapped self-assembled structures have been reported in the literature for building blocks such as peptide amphiphiles [24,63], supramolecular polymers [64], or amphiphilic diblock copolymers (assembling into disks [44], tubes [65], neuron-like tubular membranes [66], or lamellarsomes [67]). However, there are still very few examples of assemblies driven by the supply of an external source of energy.…”

Macrophage Targeting pH Responsive Polymersomes for Glucocorticoid Therapy

“…Additionally, PMPC binds to the scavenger receptor B type I (SR-BI) highly expressed in macrophages, which in turn enables the selective binding and internalisation of PMPC–PDPA polymersomes as we recently observed [13,14,15,16]. Whereas, the PDPA block bestows the pH responsive nature of polymersomes, as at pH lower than 6.2 (the PDPA pK a ) enables the polymersomes disassemble and hence release of loaded drug [17]. We have amply demonstrated [14,17,18,19,20,21,22] that such feature enables the intracellular cargo delivery, where the polymersome disassembly is confined within endosomes.…”