Superselective Targeting Using Multivalent Polymers

Despite their importance for material and life sciences, multivalent interactions between polymers and surfaces remain poorly understood. Combining recent achievements of synthetic chemistry and surface characterization, we have developed a well-defined and highly specific model system based on host/guest interactions. We use this model to study the binding of hyaluronic acid functionalized with host molecules to tunable surfaces displaying different densities of guest molecules. Remarkably, we find that the surface density of bound polymer increases faster than linearly with the surface density of binding sites. Based on predictions from a simple analytical model, we propose that this superselective behavior arises from a combination of enthalpic and entropic effects upon binding of nanoobjects to surfaces, accentuated by the ability of polymer chains to interpenetrat

Designing Multivalent Probes for Tunable Superselective Targeting

This is the author accepted manuscript. The final version is available from PNAS via http://dx.doi.org/10.1073/pnas.1500622112Specific targeting is common in biology and is a key challenge in nanomedicine. It was recently demonstrated that multivalent probes can selectively target surfaces with a defined density of surface binding sites. Here we show, using a combination of experiments and simulations on multivalent polymers, that such “superselective” binding can be tuned through the design of the multivalent probe, to target a desired density of binding sites. We develop an analytical model that provides simple yet quantitative predictions to tune the polymer’s superselective binding properties by its molecular characteristics such as size, valency, and affinity. This work opens up a route toward the rational design of multivalent probes with defined superselective targeting properties for practical applications, and provides mechanistic insight into the regulation of multivalent interactions in biology. To illustrate this, we show how the superselective targeting of the extracellular matrix polysaccharide hyaluronan to its main cell surface receptor CD44 is controlled by the affinity of individual CD44–hyaluronan interactions.This work was supported by the Marie Curie Career Integration Grant “CELLMULTIVINT,” PCIG09-GA-2011-293803 (to G.V.D.), and the European Research Council (ERC) Starting Grant “JELLY,” 306435 (to R.P.R.). D.F. acknowledges ERC Advanced Grant 227758 and EPSRC Programme Grant EP/I001352/1. T.C. acknowledges support from the Herchel Smith Fund

Polysaccharide-Blend Multilayers Containing Hyaluronan and Heparin as a Delivery System for rhBMP-2

International audienceIt is shown that blend multilayers of hyaluronan (HA) and heparin (HEP) as polyanions and poly(L-lysine) (PLL) as a polycation can be used to prepare films with different thicknesses and chemical compositions. The amounts of recombinant human BMP-2 (rhBMP-2) loaded and the fraction initially released from the films depend on the film's chemical composition. The amounts of rhBMP-2 loaded in the films are much higher for HA mass fractions of more than 0.4. The bioactivity of the rhBMP-2-loaded films is investigated on C2C12 myoblasts, which differentiates into osteoblasts in contact with the films. The alkaline phosphatase expression for cells grown on nanoblend films of various compositions falls over a unique curve. This suggests that the cells "sensing" the rhBMP-2 are not influenced by the film's chemistry. The rhBMP-2 can sustain at least three successive culture sequences while remaining bioactive, thus confirming the important and protective effect of rhBMP-2. Altogether, these results indicate that crosslinked PLL/HA films have superior properties for the incorporation of rhBMP-2 and on its long-lasting bioactivity

Dual thermo- and light-responsive coumarin-based copolymers with programmable cloud points

International audienceThis article deals with the design of a new class of dual-responsive coumarin-based copolymers, sensitive to temperature and light (UV and near infrared). These well-defined random copolymers, composed of triethylene glycol methyl ether methacrylate (TEGMA) and 6-bromo-4-hydroxymethyl-7-coumarinyl methacrylate (CMA), were synthesized via the reversible addition-fragmentation chain transfer (RAFT) process. The thermosensitivity of a series of random copolymers P(TEGMA-co-CMA) was evaluated via turbidimetry measurements and experiments have indicated the possibility of tuning the cloud points by varying the molar composition of the copolymers. A key advantage of incorporating the hydrophobic CMA units into the polymer feed is the presence of a photocleavable ester link between the coumarin group and the polymer backbone. This photosensitivity to UV irradiation was exploited to conveniently tune the hydrophilic/hydrophobic balance of the copolymer by forming carboxylic acid moieties along the polymer backbone, leading to an impressive increase in Tcp. Interestingly, it was also demonstrated that the irradiation time was an essential parameter to control the coumarin release rate from the copolymers and thus to tune and reprogram the Tcp of materials. Furthermore, we have validated the proof of concept that the LCST of coumarin-based copolymers could also be controlled upon NIR light (via two photon absorption), that might open the door for important biological applications

Cyclodextrin/paclitaxel complex in biodegradable capsules for breast cancer treatment

International audienc