Chirality Controls Reaction‐Diffusion of Nanoparticles for Inhibiting Cancer Cells

Abstract Reaction‐diffusion (RD) is the most important inherent feature of living organisms, but it has yet to be used for developing biofunctional nanoparticles (NPs). Here we show the use of chirality to control the RD of NPs for selective inhibition of cancer cells. We observe that l‐phosphotyrosine (l‐pY)‐decorated NPs (NP@l‐pYs) are innocuous to cells, but d‐pY‐decorated ones (NP@d‐pYs) selectively inhibit cancer cells. Our study shows that phosphatases, present in the culture and overexpressed on the cancer cells, dephosphorylate NP@l‐pYs much faster than NP@d‐pYs. Such a rate difference allows the NP@d‐pYs to be mainly dephosphorylated on cell surface, and thus adhere selectively on the cancer cells, resulting in poly(ADP‐ribose)polymerase (PARP)‐hyperactivation‐mediated cell death. Without phosphate groups or with premature dephosphorylation before reaching cancer cells (as in the case of NP@l‐pYs), the NPs are innocuous to cells. Moreover, NP@d‐pYs exhibit even more potent activity than cisplatin for inhibiting platinum‐resistant ovarian cancer cells (e.g., A2780‐cis). As the first example of chirality controlling a RD process of NPs for inhibiting cancer cells, this work illustrates a fundamentally new way to develop nanomedicine based on RD processes and nanoparticles.