Swartz Lab

Immunomodulation and drug delivery

We are collaborating with the Hubbell group to develop materials and molecular strategies for drug delivery to immature dendritic cells of the lymph node, and to explore the mechanisms of dendritic cell activation or tolerance induction. Our approach exploits interstitial flow to access the lymphatic system as a low resistance delivery route that leads to lymph nodes. The lymphatic system constantly drains fluid and macromolecules from the interstitial space, creating small interstitial flows in the order of 0.1-1 µm/sec. We take advantage of this basic physiological phenomenon using nanoparticle platforms of specific sizes:

- Ultra-small (25 nm) particles are convected by interstitial flow through the extracellular matrix into the draining lymphatic capillary bed

- Larger (100 nm) particles enter the lymphatics much less efficiently than ultra-small nanoparticles and therefore are likely to target peripheral more than lymph node-resident DCs.

We showed that adjuvants conjugated to small particles were highly effective at inducing immune responses against pathogens and tumors. A better understanding of the mechanisms involved in such responses is critical for a deeper understanding of lymph node targeting and for the strategic development of therapies.