Tuning cell behavior with nanoparticle shape

We investigated how the shape of polymeric vesicles, made by the exact
same material, impacts the replication activity and metabolic state of
both cancer and non-cancer cell types. First, we isolated discrete
geometrical structures (spheres and tubes) from a heterogeneous sample
using density-gradient centrifugation. Then, we characterized the cellular
internalization and the kinetics of uptake of both types of polymersomes
in different cell types (either cancer or non-cancer cells). We also
investigated the cellular metabolic response as a function of the shape of
the structures internalized and discovered that tubular vesicles induce a
significant decrease in the replication activity of cancer cells compared
to spherical vesicles. We related this effect to the significant
up-regulation of the tumor suppressor genes p21 and p53 with a concomitant
activation of caspase 3/7. Finally, we demonstrated that combining the
intrinsic shape-dependent effects of tubes with the delivery of
doxorubicin significantly increases the cytotoxicity of the system. Our
results illustrate how the geometrical conformation of nanoparticles could
impact cell behavior and how this could be tuned to create novel drug
delivery systems tailored to specific biomedical application.