Stiffness of targeted layer-by-layer nanoparticles impacts elimination half-life, tumor accumulation, and tumor penetration

Abstract

<jats:title>Significance</jats:title> <jats:p>Layer-by-layer nanoparticles (LbL NPs), comprised of a charged core substrate layered sequentially with oppositely charged polyelectrolytes, are a promising class of drug delivery carriers for cancer therapeutics with demonstrated success in lowering off-target toxicity and enhancing efficacy. However, little is known about how LbL NP stiffness alters trafficking and delivery. Herein, we report that the stiffness of targeted LbL NPs, comprised of a liposome core and tumor-targeting, polymeric outer layers, can be tuned by altering the mechanical properties of its underlying liposomal core. We also show that these changes have a significant impact on in vivo NP trafficking properties; compliant LbL NPs have longer elimination times, higher organ and tumor accumulation, and higher tumor penetration.</jats:p>