Dual-Responsive Capsules with Tunable Low Critical Solution Temperatures and Their Loading and Release Behavior

Abstract

Dual-responsive capsules sensitive to pH and temperature changes were successfully prepared by grafting random copolymer brushes of 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA) and oligo(ethylene glycol) methacrylate (OEGMA) from polydopamine (Pdop)-coated SiO2 via a surface-initiated atom-transfer radical polymerization (SI-ATRP) method with subsequent removal of the SiO2 core. The uptake and release properties of the resulting capsules are highly affected by changes in the pH values and temperature of the solution. The capsules can take up cationic dye rhodamine 6G (Rh6G) at high pH and T < LCST but not at low pH and T > LCST. In contrast, the capsules can release Rh6G at pH < 7 and temperature below the LCST, but release is less efficient under the opposite conditions. This dual-responsive property was also observed for the anionic dye methyl orange.

Photo‐Cross‐Linked Dual‐Responsive Hollow Capsules Mimicking Cell Membrane for Controllable Cargo Post‐Encapsulation and Release

“…For the LbL assembly approach new dual‐responsive photo‐cross‐linkable block copolymers poly‐( N ‐isopropyl acrylamide)‐ block ‐poly[methacrylic acid‐ co ‐2‐hydroxy‐4‐(methacryloyloxy) benzophenone] (PNMB) were realized as the anionic polyelectrolyte to build the hybrid polyelectrolyte multilayer system together with cationic poly(allylamine hydrochloride) (PAH). Compared to other thermo‐ and pH‐responsive systems reported in the literature,26, 52, 57, 58, 59 the PNMB structure has the important advantage to be both thermo‐ and pH‐responsive, and in addition, contains photo‐cross‐linkable groups. We could show that the resulting hollow capsules not only possess a robust covalent‐stabilized structure due to the photo‐cross‐linking but also exhibit tunable membrane permeability which provides good stimuli‐responsive (pH and temperature) retain and release behavior for small molecules such as doxorubicin (Dox) and for larger macromolecules, in this case rhodamine B labeled, maltosylated poly(ethyleneimine), PEI‐Mal (5K) and PEI‐Mal (25K), which can be considered as models for proteins.…”

“…One of the first bioinspired functions of artificial cell membrane to be investigated in self‐assembled systems was the ability to respond to internal stimuli such as the presence of biomolecules and enzymes,9, 10, 11, 12, 13, 14, 15 redox conditions,16, 17, 18 or ionic strength19 and pH20, 21, 22, 23 of the environment and external stimuli such as light24, 25 or temperature26, 27 to control the transport behaviors. Most of these “smart” systems developed were used to elicit cargo release by a single stimulus 28…”

“…However, there is only a limited number of literature reports available so far describing polymeric hollow capsules28, 30, 31 and polymersomes32 that can modulate drug release in response to the combinations of dual stimuli such as pH/temperature,26, 33 pH/reduction,30 temperature/reduction,32 and enzyme/enzyme 28, 34. Most of these described hollow capsule systems were degradable by redox potential30, 32 and in the presence of enzymes,28, 34 while their pH and temperature response states were far from those present in cellular compartments 26, 33. Thus, there is still a lack of multi‐responsive hollow capsules with a tunable membrane permeability that can control both, the post‐encapsulation of biomolecules in the nanometer (nm) range of up to 11 nm under physiological conditions, and their sustained release triggered by stimuli being compatible with biological processes in cells.…”

“…For most of these systems reactive enzymes as well as nanoparticles were enclosed into the inner cavity of the polymeric hollow capsules during their formation process,31, 35, 36, 37, 40 However, only very limited studies exist for the post‐encapsulation under physiological conditions of small molecules and nm‐sized proteins and polysaccharides into preformed nanocapsules 26, 44, 45, 46. Cell membranes are characterized by highly controlled and selective uptake as well as release of various biomacromolecules and thus, this feature has still to be incorporated into the membrane of polymeric hollow capsules for mimicking more realistic cell compartments.…”

“…We could show that the resulting hollow capsules not only possess a robust covalent‐stabilized structure due to the photo‐cross‐linking but also exhibit tunable membrane permeability which provides good stimuli‐responsive (pH and temperature) retain and release behavior for small molecules such as doxorubicin (Dox) and for larger macromolecules, in this case rhodamine B labeled, maltosylated poly(ethyleneimine), PEI‐Mal (5K) and PEI‐Mal (25K), which can be considered as models for proteins. One of the major goals of this study was to show that our stimuli‐responsive hollow capsules can be easily used for cargo post‐encapsulation at physiological pH and room temperature (Scheme 1), avoiding, for example, any annealing steps as known for capsules with micrometer thick membranes 26, 44…”