Conjugation of Monocarboxybetaine Molecules on Amino-Poly-p-xylylene Films to Reduce Protein Adsorption and Cell Adhesion

Abstract

A surface that resists protein adsorption and cell adhesion is highly desirable for many biomedical applications such as blood-contact devices and biosensors. In this study, we fabricated a carboxybetaine-containing surface and evaluated its antifouling efficacy. First, an amine-containing substrate was created by chemical vapor deposition of 4-aminomethyl-p-xylylene-co-p-xylylene (Amino-PPX). Aldehyde-ended carboxybetaine molecules were synthesized and conjugated onto Amino-PPX. The carboxybetaine-PPX surface greatly reduced protein adsorption and cell adhesion. The attachment of L929 cells on the carboxybetaine-PPX surface was reduced by 87% compared to the cell adhesion on Amino-PPX. Furthermore, RGD peptides could be conjugated on carboxybetaine-PPX to mediate specific cell adhesion. In conclusion, we demonstrate that a surface decoration with monocarboxybetaine molecules is useful for antifouling applications.

Conjugation of mono-sulfobetaine to alkyne-PPX films via click reaction to reduce cell adhesion

“…Due to the effectiveness of CuAAC, a much less amount of SBAZ molecules is sufficient to reach a similar level of protein/cell-resistance that is achieved by the aldehyde/amine system. In this study, 1 mg/mL (~4 mM) of SBAZ was sufficient to achieve significant resistance to protein adsorption and cell adhesion to a level, which is achieved by 50 mg/mL aldehyde-ended carboxybetaine in our previous study (Chien et al 2014). The CuAAC reaction provides a more effective tool for surface conjugation of zwitterionic molecules compared to the aldehyde-amine reaction.…”

“…Since sulfobetaine binds water tightly, we expected that the surface hydrophilicity would be increased after SBAZ immobilization. After the conjugation of SBAZ at 0.1, 1 or 5 mg/mL, the We previously conjugated aldehyde-ended carboxybetaine molecules to Amine-containing PPX for anti-fouling purposes (Chien et al 2014). Aldehyde-ended carboxybetaine molecules could be coupled to Amino-PPX, and then reduce cell adhesion and protein adsorption, but a high concentration of aldehyde-ended carboxybetaine molecules (>50 mg/mL) is needed in the conjugation to Amino-PPX in order to reduce a significant amount of cell adhesion and protein adsorption.…”

“…Recently, we utilized amino-PPX substrates for conjugation of mono-zwitterionic molecules (Chien et al 2014). Aldehyde-ended carboxybetaine molecules were synthesized and could be conjugated on the amino-PPX via the formation of imine bonds with the primary amines.…”

The synthesis of substituted amino[2.2]paracyclophanes

“…Derivatives of [2.2]paracyclophane offer an intriguing scaffold for the preparation of enantiomerically enriched molecules possessing a plane of chirality, a rigid backbone and unusual electronic properties. 1,2,3 These characteristics have been exploited in asymmetric synthesis, 1,4 as well as probes for the study of through-bond and -space electronic interactions, 5 interchromophore contact, π-π electron delocalisation, 6 photonic applications 7 as well as precursors to functionalised coatings 8,9 and atypical bioisosteres. 10,11 While amino [2.2]paracyclophanes (Figure 1) form the basis of many of these functionalised molecules there are few simple, reliable methods for the synthesis of substituted derivatives; most reactions are substrate specific.…”

“…While moderate to high yields have been reported these require very precise reaction times and conditions. 8,12,13 More common routes to aminoparacyclophanes include the Curtius rearrangement of the appropriate carboxylic acid 9,14,[15][16][17][18] or the electrophilic amination of bromoparacyclophanes. Advantages of the former strategy include facile resolution of the acid 12,19 and the ability of acids to direct functionalisation of paracyclophanes.…”