Effect of Cell Membrane‐cloaked Nanoparticle Elasticity on Nano‐Bio Interaction

Abstract Cell membrane‐cloaked nanoparticles are exploited as a promising drug carrier to enhance circulation, accumulation, penetration into tumor sites and cellular internalization. However, the effect of physicochemical properties (e.g., size, surface charge, shape, and elasticity) of cell membrane‐cloaked nanoparticles on nano‐bio interaction is rarely studied. In the present study, keeping the other parameters constant, erythrocyte membrane (EM)‐cloaked nanoparticles (nanoEMs) with different Young's moduli are fabricated by altering different kinds of nano‐core (i.e., aqueous phase core, gelatin nanoparticles, and platinum nanoparticles). The designed nanoEMs are used to investigate the effect of nanoparticle elasticity on nano‐bio interaction including cellular internalization, tumor penetration, biodistribution, blood circulation, and so on. The results demonstrate that the nanoEMs with intermediate elasticity (≈95 MPa) have a relatively higher increase in cellular internalization and inhibition of tumor cells migration than the soft (≈11 MPa) and stiff (≈173 MPa) ones. Furthermore, in vivo studies show that nanoEMs with intermediate elasticity preferentially accumulate and penetrate into tumor sites than the soft and stiff ones, while in circulation, softer nanoEMs show a longer blood circulation time. This work provides an insight for optimizing the design of biomimetic carriers and may further contribute to the selection of nanomaterials on biomedical application.