Oxidant-responsive ferrocene-based cyclodextrin complex coacervate core micelles

Abstract

Coacervate-core micelles are considered promising materials for several applications, from catalysis to drug delivery. However, oxidant-responsive coacervate-core micelles, able to undergo structural changes upon specific oxidation stimuli, are not well reported. Here, we present a novel ferrocene-dipicolinic acid derivative as redox-responsive subcomponent to be incorporated in cyclodextrin-based coacervate core micelles, C4Ms, with tuneable core structure and responsiveness towards H 2 O 2 treatment. The Fc-C4Ms are formed combining three orthogonal supramolecular interactions, namely (i) metal-to-ligand coordination between europium(III) ions and dipicolinic acid molecules, (ii) host-guest interaction between beta cyclodextrins and ferrocenes and (iii) electrostatic coacervation interaction. The micelle stability against oxidation can be controlled by varying three main parameters: (a) the core-unit structure, from monomeric metal complexes to supramolecular oligomers, (b) the H 2 O 2 equivalents and c) the ratio between redoxresponsive and non-redox-responsive bislinker. The H 2 O 2 -responsive ferrocene-based systems might have an interesting application, e.g. reactive oxygen species-mediated drug delivery.

On Complex Coacervate Core Micelles: Structure-Function Perspectives

“…Since ionic-neutral copolymers co-assemble with a broad range of oppositely charged compounds, these have been exploited to encapsulate many different types of chemical species, including linear block (co)polymers, biopolymers, such as DNA [ 13 , 14 ], proteins [ 15 ], surfactants [ 16 ], metallic complexes [ 17 , 18 ], nanoparticles, and dendrimers [ 19 ]. The resultant core/shell hydrocolloids are referred to in the literature as complex coacervate core micelles (C3Ms), polyion complex (PIC) micelles, block ionomer complexes (BIC) and (micellar) interpolyelectrolyte complexes (IPEC), among others.…”

“…An overview of small therapeutics encapsulated in C3Ms is given in Table 1C. Much of the appeal of C3Ms as nanocarriers lies in their programmable nature, which enables triggered release of cargo in response to specific stimuli [ 17 , 145 ]. In addition, the neutral corona block endows stealth character, which increases circulation times and reduces cytotoxicity, while the rather small micellar dimensions prevent fast renal clearance.…”

Response of metal-coordination-based polyelectrolyte complex micelles to added ligands and metals

“…23,24 In this study, the Zn/LEO ratio is kept at 1/1, at which Zn-LEO can form linear coordination polymers, such that each coordination site carries a net charge of À2. For lanthanides (Ln), we fix the Ln/LEO ratio at 1/1.5, thereby producing 3D network structures such that each coordination unit carries 3 negative charges 26 (Scheme 1). These anionic coordination polymers assemble strongly with the cationic P2MVP 128 -b-PEO 477 copolymers and provide well-controlled polyelectrolyte micelles (M-C3Ms), with a core with a linear supramolecular polymer in the case of Zn, and branched supramolecular polymer in the case of Ln.…”

100th Anniversary of Macromolecular Science Viewpoint: Attractive Soft Matter: Association Kinetics, Dynamics, and Pathway Complexity in Electrostatically Coassembled Micelles

“… 4 , 24 C3Ms can be constructed by combining ionic-neutral diblock copolymers (dbp) with a plethora of oppositely charged species, including linear and branched (synthetic) polyelectrolytes, polysaccharides, 25 DNA, 26 proteins, 27 peptides, 28 dendrimers, 29 multivalent ions, 30 − 32 and metallic complexes. 33 Their application potential spans from materials science to nanomedicine and is largely dependent on the chemical nature of the constituent and embedded building blocks. Encapsulation of biomolecules, such as DNA, RNA, and proteins, for protective delivery and controlled release purposes is one of the most active areas of fundamental and applied research on C3Ms.…”