We report the assembly of low-fouling polymer capsules with engineered deconstruction properties by using a combination of layer-by-layer (LbL) assembly and click chemistry. Preformed, hydrogen-bonded multilayers of alkyne-functionalized poly(N-vinyl pyrrolidone) (PVPON(Alk)) and poly(methacrylic acid) (PMA) assembled at pH 4 on silica particles were cross-linked with a bisazide linker (containing a disulfide link) through alkyne-azide click chemistry. Following dissolution of the silica template particles, and altering the solution pH to 7.2 to disrupt hydrogen bonding between PVPON(Alk) and PMA to effect removal of PMA, stable, cross-linked PVPON capsules were obtained. The presence of the disulfide bond in the bisazide linker endowed the PVPON capsules with degradable characteristics under model intracellular conditions. The capsules deconstructed within 4 h in the presence of 5 mM glutathione. The cross-linked PVPON(Alk) multilayers (assembled on silica particles) were low-fouling to a range of proteins, including fibrinogen, lysozyme, immunoglobulin G, and bovine serum albumin. Further, MTT assays showed that the PVPON capsules had no effect on the proliferation of cells from a human colon cancer cell line (LIM1899), indicating negligible cytotoxicity toward the LIM1899 cells. The low-fouling, degradable, and low cytotoxicity characteristics of the PVPON capsules makes them attractive as a platform for the development of advanced therapeutic delivery systems.

Engineered particles and capsules prepared by the layer-by-layer assembly of interacting polymers have potential in drug delivery and microreactor applications. Herein, we report a new, versatile method to covalently stabilize and functionalize polymer-coated particles and polymer capsules utilizing robust and efficient thiol−ene chemistry.

A universal method of assembling low‐biofouling films that can be engineered to promote the specific adhesion and growth of cells onto surfaces is described (see image). Click chemistry and the layer‐by‐layer method are used to assemble films of poly(ethylene glycol) acrylate, which are functionalized with the adhesion‐promoting peptide, arginine‐glycine‐aspartate (RGD).

The combination of click chemistry and layer-by-layer (LbL) assembly provides a useful and convenient means of preparing functional, covalently stabilized films and capsules. Herein, we examine various parameters that affect the buildup of click-LbL assembled multilayers of azide- and alkyne-modified poly(acrylic acid) (PAAAz and PAAAlk, respectively). We demonstrate that film thickness and morphology can be tailored by varying the assembly conditions. The thicknesses of multilayers assembled from PAAAz and PAAAlk [(PAAAz/PAAAlk)5] on planar substrates varied from ∼70 nm when assembled at pH 2.5 to 10 nm when prepared at pH 4. Increasing the ionic strength of the adsorption solution resulted in an increase in the (PAAAz/PAAAlk)5 film thickness, with a maximum of ∼30 nm observed for solutions with ionic strengths of 150 mM and greater. A deposition time of 5 min was found to give close to saturated adsorbed layer amounts. Additionally, the influence of the click moieties on multilayer assembly was investigated. By altering the azide content of PAAAz and maintaining the alkyne content of PAAAlk at ∼15%, the thicknesses of (PAAAz/PAAAlk)5 films were shown to increase exponentially from about 20 nm at 5% azide functionalization of PAAAz to 90 nm at 30% azide functionalization of PAAAz. Furthermore, atomic force microscopy measurements showed distinct morphological changes (i.e., enhanced porosity and/or creases and folds) for (PAAAz/PAAAlk)5 films prepared from PAAAz with different azide contents at pH 3.5 when subjected to basic conditions (pH 10). This was attributed to the different cross-linking degree between the multilayers. The current study was extended to the assembly of hollow polymer capsules to determine an optimum range of 10−20% azide functionalization of PAAAz for the assembly of click polymer capsules.