The potential of confined water to enhance heat transfer has remained an open question, limiting its application in nanomedicine. At the same time, the full theranostic potential of metal-phenolic networks (MPNs) in imaging-guided therapy has yet to be realized. Herein, we demonstrate that hollow iron-tannic acid nanoparticles (Fe-TA NPs), synthesized by poly(vinylpyrrolidone)-mediated dynamic coordination switching, can utilize confined water to address both challenges. The nanoconfined water organizes into a highly ordered hydrogen-bonded layer that enhances photothermal efficiency and magnetic resonance imaging performance by facilitating heat transfer and promoting Larmor frequency matching. Beyond this, the platform exhibits potent redox activity, generating reactive oxygen species and depleting glutathione via Fenton reaction and Michael addition. When loaded with doxorubicin, it achieves stimuli-responsive drug release and synergistic tumor eradication through combined photothermal, chemo, and oxidative stress therapies, effectively inducing apoptosis and immunogenic cell death. This work provides a multifaceted theranostic platform and highlights confinement-enhanced hydrogen bonding as a key design principle for future cancer nanomedicine.
An et al. (Tue,) studied this question.