Bio-Inspired Polymer Microparticles for Targeted Recognition and Response

Abstract

Microbeads and microcapsules are container structures that are frequently used in biomedical applications. In this dissertation, we have sought to impart new functionalities to these particles, inspired by phenomena observed with biological cells. We have engineered polymer microparticles that recognize and respond to specific species from the surroundings (e.g. cells, polymer chains, metal ions). Three classes of new microparticles are reported, which are each reminiscent of a different type of biological cell in terms of recognition capabilities and response.

In the first part of this dissertation, we create functionalized microbeads from the biopolymer, chitosan, and use these to selectively recognize and capture Circulating Tumor Cells (CTCs) from blood. The microbeads are functionalized with a protein (streptavidin) and packed into an array within a microfluidic device. Blood samples with biotin-labeled CTCs are flowed over the packed bed of chitosan beads. Similar to how macrophages adhere to foreign bacteria (i.e. antibody-antigen interactions), the streptavidin-labeled chitosan beads can selectively recognize and adhere to the biotin-labeled CTCs. We show that such a packed bed of chitosan beads could serve as an inexpensive platform for customized capture of different rare cells (cancer cells, stem cells etc) from blood.

In the next study, we develop a class of microbeads that undergo clustering (aggregation) in the presence of specific polymers. The inspiration for this comes from the cells (e.g., platelets) and polymers involved during the formation of blood clots. Our system consists of chitosan microbeads coated with cyclodextrins (sugar molecules with a hydrophobic binding pocket), which are then exposed to a polymer that is decorated with hydrophobic units. The particles bind to the polymer chains via hydrophobic interactions and in turn, the particles are induced to form clusters. Subsequently, the polymer precipitates and forms a matrix around the particle clusters, leading to a structure that is reminiscent of a blood clot (platelets enveloped by a mesh of fibrin chains).

Lastly, we develop a class of microparticles that have the ability to selectively destroy other microparticles. The inspiration here is from the body's immune system, where cells like the killer T cells selectively destroy cancer and virus infected cells without harming healthy cells. Towards this end, we synthesize two types of microparticles: chitosan capsules that contain the enzyme glucose oxidase (GOx), and beads of a different biopolymer, alginate that are crosslinked with copper (Cu2+) ions. The chitosan capsules enzymatically convert glucose from the surroundings into gluconate ions. When these capsules approach the alginate/copper beads, the gluconate ions chelate the copper ions, leading to the disintegration of the alginate beads. Other beads that do not contain Cu2+ are not affected in this process.