Structure and functionalization of thermoresponsive nanogels as key points for drug delivery

A. WOLFEL; E.R. OSORIO-BLANCO; H. WANG; C.I. ALVAREZ IGARZABAL ; M. CALDERÓN

Simposio; Virtual International Symposium on Nano/Microgels; 2020

INSTITUTO DE QUIMICA MEDICA

The scientific advances towards nanogels (NGs) applications have revealed the need for a precise control over their sizes, polydispersity, architectures and functionalization, which are determinant for biomedical applications. In this work, we propose a methodology that enables an easy post-synthesis modification of the architecture of thermoresponsive NGs and introduces orthogonally-modifiable functional groups (FGs). For this purpose, we studied the incorporation of a cleavable crosslinker in the synthesis of poly(N-isopropylacrylamide) and poly(N-isopropylmethacrylamide) based NGs. The crosslinker (+)-N,N´-diallyltartradiamide (DAT) presents vicinal diols which can be easily cleaved by sodium periodate aqueous solutions in a post-synthesis step. As a result, the breakdown crosslinks changed the NGs structure while yielded valuable α-oxoaldehyde FGs. This particular variety of aldehyde groups is useful for further chemical derivatizations and often used to undergo bio-orthogonal reactions.Parameters such as monomers and crosslinkers reactivity, or the initiation method used, modified the spatial distribution of the cleavable crosslinker. Therefore, differentiated structural changes were promoted in the NGs after their treatment with periodate. The α oxoaldehyde groups were used for the covalent linkage of doxorubicin hydrochloride (DOXO) through pH-sensitive hydrazone bonds. In addition, the effects of the structural changes on the loading of bovine serum albumin, as a model bio-macromolecule, were evaluated. We believe that the proposed chemical strategy could be a valuable tool for improvement of nanodevices through structural modifications and functionalization.