Polydopamine-like Coatings as Payload Gatekeepers for Mesoporous Silica Nanoparticles

Abstract

We report the use of bis-catecholic polymers as candidates for obtaining effective, tunable gatekeeping coatings for mesoporous silica nanoparticles (MSNs) intended for drug release applications. In monomers, catechol rings act as adhesive moieties and reactive sites for polymerization, together with middle linkers which may be chosen to tune the physicochemical properties of the resulting coating. Stable and low-toxicity coatings (pNDGA and pBHZ) were prepared from two bis-catechols of different polarity (NDGA and BHZ) on MSN carriers previously loaded with rhodamine B (RhB) as a model payload, by means of a previously reported synthetic methodology and without any previous surface modification. Coating robustness and payload content were shown to depend significantly on the workup protocol. The release profiles in a model physiological PBS buffer of coated systems (RhB@MSN@pNDGA and RhB@MSN@pBHZ) showed marked differences in the "gatekeeping" behavior of each coating, which correlated qualitatively with the chemical nature of their respective linker moieties. While the uncoated system (RhB@MSN) lost its payload almost completely after 2 days, release from RhB@MSN@pNDGA was virtually negligible, likely due to the low polarity of the parent bis-catechol (NDGA). As opposed to these extremes, RhB@MSN@pBHZ presented the most promising behavior, showing an intermediate release of 50% of the payload in the same period of time.

Chemistry of Polydopamine – Scope, Variation, and Limitation

“…Formation of polymers by oxidation of heteroanalogues of DA wherein CH 2 groups are replaced by heteroatoms, such as N, O or S is rarely found in literature (Scheme ). Dihydroxybenzaldehyde‐(3,4‐dihydroxybenzoyl)‐hydrazone is an example with X = CH and Y=NH in a dehydrogenated form. In fact, it could be autoxidized by air forming polymer coatings (Scheme ).…”

“…General formula of DA analogues with CH 2 -groups exchanged by heteroatoms (top), polymer formation by air-oxidation of 3,4-dihydroxybenzaldehyde (3,4-dihydroxybenzoyl)-hydrazone (bottom). [118] reactive. In fact, oxidations under the standard conditions were unsuccessful until finally APS was applied under harsh conditions.…”

Bio-Applications of Multifunctional Melanin Nanoparticles: From Nanomedicine to Nanocosmetics

“…It is worth to mention that these reactions can proceed in water solution, and that the coupling products remain quite stable in time [87]. Since adhesion to surface involves the catechol, Ruiz-Molina and coworkers proposed also the use of PDA analogous demonstrating that some bis-catecholic polymers can be used to coat mesoporous silica NP in order to slow down the release of preloaded model molecules [88]. Recently, Messersmith and coworkers demonstrated that, indeed, having both catechols and amines combined in the same functional monomer is advantageous for the final adhesion strength: decoupling the two kinds of functional groups, in fact, prevents cooperative effects with an observable worsening of the adhesive performances [89].…”

Bioinspired Functional Catechol Derivatives through Simple Thiol Conjugate Addition

“…In the first case, bis-catechols 6 could be used as flexible bidentate ligands forc oordination chemistry.I nt his regard, similar bis-catechol molecules have been used successfully by our group as ligands for the preparation of coordinationp olymer particles, as well as polydopamine-like gatekeeping coatings. [17] With regard to catechol-thiols 5,t he terminal thiol should allow further conjugation of the catechol-thiol to functional moieties bearing electrophilic reactive ends, such as vinyl, acrylate, or isocyanate groups, thus providing an straightforward alternative route to functional catechols.…”