Developing tumor-specific drug delivery systems with minimized off-target cargo leakage remains an enduring challenge. In this study, inspired from the natural cryptobiosis explored by certain organisms and stimuli-responsive polyphenol‒metal coordination chemistry, doxorubicin (DOX)-conjugated gelatin nanoparticles with protective shells formed by complex of tannic acid and Fe^III (DG@TA-Fe^III NPs) were successfully developed as an “AND” logic gate platform for tumor-targeted DOX delivery. Moreover, benefiting from the well-reported photothermal conversion ability of TA-Fe^III complex, a synergistic tumor inhibition effect was confirmed by treating 4T1 tumor-bearing mice with DG@TA-Fe^III NPs and localized near-infrared (NIR) laser irradiation. As a proof of concept study, this work present a simple strategy for developing “AND” logic gate platforms by coating enzyme-degradable drug conjugates with detachable polyphenol‒metal shells.

开发具有最小目标外货物泄漏的肿瘤特异性药物输送系统仍然是一个持久的挑战。在这项研究中，受某些生物体探索的自然隐匿性生物和刺激响应多酚‒金属配位化学的启发，阿霉素（DOX）缀合的明胶纳米颗粒具有由鞣酸和Fe ^III的复合物形成的保护壳（DG @ TA-Fe ^III NPs）已成功开发为用于肿瘤靶向DOX递送的“ AND”逻辑门平台。此外，得益于广为报道的TA-Fe ^III复合物的光热转化能力，通过用DG @ TA-Fe ^III处理4T1荷瘤小鼠证实了协同的抑瘤作用NP和局部近红外（NIR）激光照射。作为概念研究的证明，这项工作提出了一种通过用可分离的多酚‒金属壳包被可酶降解的药物偶联物来开发“ AND”逻辑门平台的简单策略。