Biointerface properties of core-shell poly(vinyl alcohol)-hyaluronic acid microgels based on chemoselective chemistry

Chemoselective chemistry is one of the main synthetic strategies for the design of bioactive constructs. In this contribution we report on the fabrication of core-shell microgel particles, obtained by "click chemistry" and "inverse emulsion droplets" techniques. Azido and alkyne derivatives of poly(vinyl alcohol) (PVA) in a 1:2 mol ratio of functional groups, respectively, were crosslinked by click chemistry method. The microgel particles were spherical in shape with an average diameter of about 2 μm and with a narrow size distribution. Residual unreacted alkyne groups present on the particle surface were "clicked" with an azido-grafted hyaluronic acid. These microgel particles with a PVA core and a hyaluronic acid shell were tested for bioorthogonality, that is, for the absence of cytotoxicity in the presence of unreacted clickable functionalities and demonstrated a remarkable ability to target adenocarcinoma colon cells (HT- 29) as well as to release locally the antitumor drug, doxorubicin. Internalization process was studied in connection with the presence of hyaluronic acid on the microgel particles surface. In this paper we introduce a concept device based on chemoselective chemistry, which may contribute to the design of micro- and nanoplatforms having controlled and multifunctional structures.