(468b) Functional Polyion Complex Vesicles Enabled By Supramolecular Reversible Coordination Polyelectrolytes

Polymer vesicles are a type of aggregates with a hollow structure that is often widely used as carriers, containers, nanoreactors, or biosensors for various functionality compounds.^[1] The traditional preparation method is through an amphiphilic block copolymer. These vesicles have high structural stability and good biocompatibility, but the hydrophobic nature of the membrane in such amphiphilic polymersomes prevents the penetration of hydrophilic solutes, limiting their functionality as semipermeable container systems. In 2006, Kataoka added a new class of vesicles, called ‘PICsomes’ (Polyion complex vesicles), wherein carefully length-matched pairs of charged blocks of varying chemistry were chosen.^[2] These PICsomes have interesting, and to some extent, unique properties, in particular regarding permeability for hydrophilic solutes. And it has the potential to use as vehicles for biomolecules, for example, proteins and RNA.^[3] It seems likely that the success, in this case, is due to the matching of chain lengths, which ensures that any cationic/anionic polyelectrolyte pair is automatically also (approximately) charge-matched. With unmatched pairs, it is far more difficult to satisfy charge matching without creating packing problems. Unfortunately, the stringent matching conditions on the charged block’s lengths are synthetically challenging and make it difficult to explore variations in polymer chain length and type.

This work innovatively proposes a new method for preparing functional vesicles with supramolecular coordination polyelectrolytes. By using the coordination between metal M²⁺ and ligand L₂EO₄, this work prepared a coordination polyanion with reversible structure and adjustable chain length, which was further assembled with polycation-neutral block polymer PEO₄₅-b-PMETAC_n to form a controllable polyelectrolyte vesicle.^[4] A unique feature is that the length of the coordination polyanion is not fixed, but adjusts itself so that no dangling charged chains occur and the excess charge on the assembly surface remains small. This feature appears to be beneficial for the appearance of the lamellar morphology and, hence, well-defined vesicles. We indeed obtained PICsomes, and we investigated their morphology and how it is controlled by experimental parameters, such as charge ratio, diblock copolymers’ charge block length, different metals. We find that the formation of stable vesicles requires sufficiently long covalent charged blocks (ratio charge/neutral » 1), which is in agreement with the results of the literature. As long as this condition is satisfied, the length of the charged block can be varied. Different metal-coordinated M-L₂EO₄ polymers produce similar vesicles with different properties and functions, depending on the selected metal ion. As an example, we prepare Mn-based PICsomes, which exhibited a magnetic relaxivity about 4.3 mM^-1 s^-1, as well as enhanced contrast in vitro MR imaging tests. Hence, our method for preparing PIC vesicles is simple and robust, and it introduces polymersomes with novel features, applications of which are worth exploring.

[1] D. E. Discher, A. Eisenberg, Science 2002, 297, 967-973.

[2] A. Koide, A. Kishimura, K. Osada, W. D. Jang, Y. Yamasaki, K. Kataoka, J. Am. Chem. Soc. 2006, 128, 5988–5989.

[3] Y. Anraku, A. Kishimura, M. Oba, Y. Yamasaki, K. Kataoka, J. Am. Chem. Soc. 2010, 132, 1631–1636.

[4] Wenjuan Zhou, Jiahua Wang, Peng Ding, Xuhong Guo, Martien A. Cohen Stuart and Junyou Wang, Angew. Chem. Int. Ed. 2019, 58, 8494–8498.