“Killer” Microcapsules That Can Selectively Destroy Target Microparticles in Their Vicinity

Abstract

We have developed microscale polymer capsules that are able to chemically degrade a certain type of polymeric microbead in their immediate vicinity. The inspiration here is from the body's immune system, where killer T cells selectively destroy cancerous cells or cells infected by pathogens while leaving healthy cells alone. The "killer" capsules are made from the cationic biopolymer chitosan by a combination of ionic cross-linking (using multivalent tripolyposphate anions) and subsequent covalent cross-linking (using glutaraldehyde). During capsule formation, the enzyme glucose oxidase (GOx) is encapsulated in these capsules. The target beads are made by ionic cross-linking of the biopolymer alginate using copper (Cu) cations. The killer capsules harvest glucose from their surroundings, which is then enzymatically converted by GOx into gluconate ions. These ions are known for their ability to chelate Cu cations. Thus, when a killer capsule is next to a target alginate bead, the gluconate ions diffuse into the bead and extract the Cu cross-links, causing the disintegration of the target bead. Such destruction is visualized in real-time using optical microscopy. The destruction is specific, i.e., other microparticles that do not contain Cu are left undisturbed. Moreover, the destruction is localized, i.e., the targets destroyed in the short term are the ones right next to the killer beads. The time scale for destruction depends on the concentration of encapsulated enzyme in the capsules.

Onion-like multilayered polymer capsules synthesized by a bioinspired inside-out technique

“…2 . Note that, to create biopolymer gel cores with diameters <1 mm, we resorted to a microfluidic technique developed in our laboratory in which pulses of compressed gas are used to shear off biopolymer-bearing aqueous droplets from the tip of a capillary 36 , 37 . Once cores of a given size are created, the rest of the procedure is the same as shown in Fig.…”

“…5a where the inner layer is nonionic while the outer layer is anionic. To make this capsule, we first created a pH-insensitive core of chitosan (an amine-rich polysaccharide) cross-linked with glutaraldehyde (GA) 36 , 49 . The core was made as before by adding the chitosan solution drop-wise into a solution of the GA; note that GA forms covalent bonds between the amines on chitosan 32 .…”

“…This was then added drop-wise (as above) to a solution of 2 wt% GA. After incubation for 24 h, chitosan gels crosslinked by GA were obtained. To form gel cores with diameters <1 mm, a pulsed-gas micro-capillary device was used 36 , 37 . The biopolymer solution of interest was sent through a capillary of 80-µm inner diameter at a flow rate of 3 µl/min.…”

Leveraging synthetic particles for communication: from passive to active systems

“…3B). 24 "Killer" microcapsule were obtained by encapsulating the enzyme GOx in chitosan microcapsules. Gluconate ions were formed after the chemical input glucose diffused inside.…”

“…The gluconate ions then chelate away the cross-linking Cu 2+ cations of the alginate bead, leading to its degradation. 24 (C) Interactive communication between Janus particles. Chemical input, lactose, is hydrolyzed by β-galactosidase (β-Gal) on the sender (S1 gal ) to generate glucose, which is oxidized by GOx into gluconic acid on the receiver (S2 gox ).…”