A focused delivery of immune modulating molecules to lymph nodes is of high relevance to simultaneously stimulate multiple immune cell populations and trigger successful immune response (for instance during vaccination or cancer immunotherapy). Several highly potent small molecules have been developed e.g. imidazoquinolines (IMDQ) for toll-like receptor (TLR) 7/8 stimulation. However, they cause severe systemic inflammatory toxicities and cannot be applied as such for immunotherapeutic purposes.<br/>Nano-sized carrier systems can suppress their systemic distribution and instead facilitate their focused delivery to draining lymph nodes after subcutaneous injection. For successful IMDQ conjugation, the reactive ester approach has been established as versatile tool to generate core-crosslinked micellar nanogels via self-assembled amphiphilic reactive ester block copolymers.<br/>We implemented this strategy for the first time to poly(carbonate)-based precursor polymers bearing a hydrolysable polymer backbone. Via core-crosslinking and hydrophilization of the self-assembled block copolymer micelles we yielded degradable nanogels further equipped with fluorescent dyes for monitoring and IMDQ for lymph node focused immune cell activation. We opt for the degradability of the carrier system to regulate transient immune stimulation and anticipate higher biocompatibilitiy for <i>in vivo</i> applications.

Degradable poly(carbonate)-nanogels for focused delivery of immune stimulatory small molecules to draining lymph nodes

ACS Spring Meeting 2021

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