X‐ray‐Controlled Bilayer Permeability of Bionic Nanocapsules Stabilized by Nucleobase Pairing Interactions for Pulsatile Drug Delivery

The targeted and sustained drug release from stimuli‐responsive nanodelivery systems is limited by the irreversible and uncontrolled disruption of the currently used nanostructures. Bionic nanocapsules are designed by cross‐linking polythymine and photoisomerized polyazobenzene (PETAzo) with adenine‐modified ZnS (ZnS‐A) nanoparticles (NPs) via nucleobase pairing. The ZnS‐A NPs convert X‐rays into UV radiation that isomerizes the azobenzene groups, which allows controlled diffusion of the active payloads across the bilayer membranes. In addition, the nucleobase pairing interactions between PETAzo and ZnS‐A prevent drug leakage during their in vivo circulation, which not only enhances tumor accumulation but also maintains stability. These nanocapsules with tunable permeability show prolonged retention, remotely controlled drug release, enhanced targeted accumulation, and effective antitumor effects, indicating their potential as an anticancer drug delivery system. X‐ray‐responsive bionic nanocapsules with reversible and tunable permeability are prepared by cross‐linking the self‐assembled triblock polymer poly(ethylene glycol)‐b‐polythymine‐b‐polyazobenzene (PETAzo) with adenine‐modified zinc sulfide nanoparticles (ZnS‐A NPs) through nucleobase pairing. The ZnS‐A NPs cross‐link PETAzo and convert X‐rays to UV light to induce azobenzene isomerization, which allows controlled diffusion of the active payloads across the bilayer membrane.