Grafting with RAFT-gRAFT Strategies to Prepare Hybrid Nanocarriers with Core-shell Architecture

Abstract

Stimuli-responsive polymer materials are used in smart nanocarriers to provide the stimuli-actuated mechanical and chemical changes that modulate cargo delivery. To take full advantage of the potential of stimuli-responsive polymers for controlled delivery applications, these have been grafted to the surface of mesoporous silica particles (MSNs), which are mechanically robust, have very large surface areas and available pore volumes, uniform and tunable pore sizes and a large diversity of surface functionalization options. Here, we explore the impact of different RAFT-based grafting strategies on the amount of a pH-responsive polymer incorporated in the shell of MSNs. Using a "grafting to" (gRAFT-to) approach we studied the effect of polymer chain size on the amount of polymer in the shell. This was compared with the results obtained with a "grafting from" (gRAFT-from) approach, which yield slightly better polymer incorporation values. These two traditional grafting methods yield relatively limited amounts of polymer incorporation, due to steric hindrance between free chains in "grafting to" and to termination reactions between growing chains in "grafting from." To increase the amount of polymer in the nanocarrier shell, we developed two strategies to improve the "grafting from" process. In the first, we added a cross-linking agent (gRAFT-cross) to limit the mobility of the growing polymer and thus decrease termination reactions at the MSN surface. On the second, we tested a hybrid grafting process (gRAFT-hybrid) where we added MSNs functionalized with chain transfer agent to the reaction media containing monomer and growing free polymer chains. Our results show that both modifications yield a significative increase in the amount of grafted polymer.

Keywords: RAFT polymerization; core-shell hybrid mesoporous silica nanoparticles; grafting strategies; pH-responsive polymeric shell; smart nanocarriers.

Figure 1

Grafting strategies used to incorporate a pH-responsive polymer on the surface of mesoporous silica nanoparticles (MSNs). In the “grafting from” approach (gRAFT-from) the monomer 2–(diisopropylamino) ethyl methacrylate (DAEM, light blue spheres) polymerization is mediated by the CTA (dark blue spheres) anchored at the surface of the MSNs (porous red spheres), therefore, the polymer chains (light blue lines) grow anchored to the MSN surface. When the same strategy is performed in the presence of a crosslinker (gRAFT-cross), a polymer gel shell is obtained. In the “grafting to” approach (gRAFT-to), previously synthesized RAFT polymer chains (light blue lines) with a carboxylic acid end-group (blue sphere) are grafted to the surface of MSNs, by reaction between the chain end and the primary amine groups decorating the MSN surface (green spheres). In the “hybrid grafting” approach (gRAFT-hybrid) the polymerization is initiated in solution in the absence of MSNs (A). When the polymerization conversion reaches ca. 50%, the MSNs (porous red spheres) functionalized with CTA (dark blue spheres) are added to the reactional medium containing the monomer (DAEM, light blue spheres) and the growing polymer chains (light entangled blue lines) and the reaction proceeds for 24 h (B). During this time, there are free chains and chains anchored to MSNs chains simultaneously growing, with termination reactions between free and grafted chains occurring to produce a polymer shell with a broad chain size distribution (C).

Figure 2

TEM image of the MSNs with the pore structure. Scale bar = 50 nm.

Figure 3

Schematic illustration of the preparation of functionalized MSNs. Zeta-potential values measured at pH = 5.6 reflect the change in surface charge upon surface modification.

Figure 4

Strategies for surface-initiated RAFT polymerization (gRAFT-from) using a dithioester CTA (equivalent for a trithiocarbonate CTA). In the R-group approach, the RAFT is immobilized by the R group and the grafted polymer chains grow from the surface with the propagating radicals easily accessible on the terminal end for the chain-transfer reactions. In the Z-group approach, the RAFT is immobilized by the Z group, the polymer chains grow in solution and the chain transfer reactions occur near the surface of the material, hampered by steric hindrance from the neighboring attached polymer chains and by the low availability of the chain end-groups.