Protein-carbohydrate interactions are involved in a wide variety of cellular recognition processes including cell growth regulation, differentiation and adhesion, the immune response, and viral or bacterial infections. A common way for bacteria to achieve adhesion is through their fimbriae which possess cellular lectins that can bind to complementary carbohydrates on the surface of the host tissues. In this work, we synthesized glycopolymers using reversible addition-fragmentation chain transfer (RAFT) polymerization which were subsequently immobilized on a sensor surface for studies of bacterial adhesion by quartz crystal microbalance with dissipation (QCM-D). Ricinus communis Agglutinin (RCA120), a galactose specific lectin, was first studied by QCM-D to determine the specific lectin interactions to the different glycopolymers-treated surfaces. Subsequently, Pseudomonas aeruginosa PAO1 (a Gram-negative bacterium with galactose-specific binding C-type lectin (PA-IL)) and Escherichia coli K-12 (a Gram-negative bacterium with mannose-specific binding lectin) were then used as model bacteria to study bacterial adhesion mechanisms on different polymer-treated sensor surfaces by the coupled resonance theory. Our results showed that lectin-carbohydrate interactions play significant roles in comparison to the nonspecific interactions, such as electrostatic interactions. A significantly higher amount of P. aeruginosa PAO1 could adhere on the glycopolymer surface with strong contact point stiffness as compared to E. coli K-12 on the same surface. Furthermore, in comparison to E. coli K-12, the adhesion of P. aeruginosa PAO1 to the glycopolymers was found to be highly dependent on the presence of calcium ions due to the specific C-type lectin interactions of PA-IL, and also the enhanced bacterial adhesion is attributed to the stiffer glycopolymer surface in higher ionic strength condition.

In this study, galactose-based nanogels were prepared by reversible addition-fragmentation chain transfer process to facilitate the targeted delivery of iodoazomycin arabinofuranoside (IAZA), a clinical drug for imaging solid hypoxic tumors, and evaluate its role in hypoxia-selective (radio)theranostic (therapy + diagnostic) management of therapy-resistant cancer cells. The nanogels have a cross-linked temperature-responsive core and a dense carbohydrate shell. Their thermoresponsive nature allowed the controlled encapsulation of IAZA drug for targeted delivery and release in hypoxic hepatocellular carcinoma via asialoglycoprotein receptor-mediated uptake. The synthesized nanogel-IAZA delivery systems demonstrated a stable, nonburst release of IAZA over 10 h with up to 0.6 mM loading capacity of IAZA within the nanogel. The cytotoxicity evaluations of the nanogels demonstrated that they are relatively nontoxic in multiple cell lines. The radiosensitization studies indicated that IAZA in encapsulated form offers a superior radiosensitization of hypoxic cells (sensitizer enhancement ratio for IAZA alone, 1.33; 1.62 for nanogel encapsulated IAZA). These studies suggest that galactose-based nanogels may serve as a versatile drug delivery system for IAZA (and other azomycin-based agents) and enable its hypoxia-selective multimodal theranostic applications to manage hypoxic solid (hepatocellular) tumors by facilitating position/single photon emission tomography-based imaging, external beam radiation therapy, and in situ molecular radiotherapy.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for diseases such as bacteremia, chronic lung infection, and acute ulcerative keratitis. P. aeruginosa induced diseases can be fatal as the exotoxins and endotoxins released by the bacterium continue to damage host tissues even after the administration of antibiotics. As bacterial adhesion on cell surfaces is the first step in bacterial based pathogen infections, the control of bacteria-cell interactions is a worthwhile research target. In this work, thermally responsive poly(N-isopropylacrylamide) [P(NIPAAm)] based biomimetic surfaces were developed to study the two major bacterial infection mechanisms, which is believed to be mediated by hydrophobic or lectin-carbohydrate interactions, using quartz crystal microbalance with dissipation. Although, a greater number of P. aeruginosa adhered to the NIPAAm homopolymer modified surfaces at temperatures higher than the lower critical solution temperature (LCST), the bacterium-substratum bond stiffness was stronger between P. aeruginosa and a galactose based P(NIPAAm) surface. The high bacterial adhesion bond stiffness observed on the galactose based thermally responsive surface at 37 °C might suggest that both hydrophobic and lectin-carbohydrate interactions contribute to bacterial adhesion on cell surfaces. Our investigation also suggests that the lectin-carbohydrate interaction play a significant role in bacterial infections.

Temperature-responsive hyperbranched polymers containing primary amines as pendent groups have been synthesized for solid-liquid separation of kaolinite clay suspension. The effects of temperature, polymer charge density, and polymer architecture on particle flocculation have been investigated. Suspensions treated with the temperature-responsive amine-based hyperbranched polymers showed remarkable separation of the fine particles at a low polymer dosage of 10 ppm and at testing temperatures of 40 °C. In comparison to other polymers studied (linear and hyperbranched homopolymers and copolymers), the temperature-responsive amine-based hyperbranched copolymers showed better particle flocculation at 40 °C, as evidenced by the formation of a thinner sediment bed without compromising the amount of clay particles being flocculated. This superior solid-liquid separation performance can be explained by the hydrophobic interaction of PNIPAM segments on particle surfaces or the capture of additional free particles or small floc due to the exposure of buried positive charges (because of the phase separation of the hydrophilic amines and hydrophobic PNIPAM part) at temperatures above the lower critical solution temperature (LCST).

A dual pH and glucose responsive boronic acid containing nanofiber was constructed for the reversible capture and release of lectins. The effects of surface groups and pH values on selective lectin capture were investigated by fluorescence microscopy. Compared to the pristine nanofibrous membrane, glucose and galactose functionalized nanofiber surfaces showed significantly higher capture of ConA and Jacalin, under alkaline conditions. On the other hand, treatment of the modified nanofibers with an acidic solution resulted in the detachment of both the lectins and glycopolymers from the nanofiber surface. As expected, once the glycopolymers are displaced, no lectins were adhered to the nanofiber surface under alkaline conditions. These functional nanofibers can therefore be easily modified and hence can be used for quick removal of selective proteins or toxins from the solution.