Electrochemical therapy (EChT), by inserting electrodes directly into tumors to kill cancer cells under direct current (DC), is clinically used in several countries. In EChT, the drastic pH variation nearby the inserted electrodes is the main cause of tumor damage. However, its limited effective area and complex electrode configuration have hindered the clinical application of EChT in treating diverse tumor types. Herein, a conceptually new electric cancer treatment approach is presented through an electro‐driven catalytic reaction with platinum nanoparticles (PtNPs) under a square‐wave alternating current (AC). The electric current triggers a reaction between water molecules and chloride ions on the surface of the PtNPs, generating cytotoxic hydroxyl radicals. Such a mechanism, called electrodynamic therapy (EDT), enables effective killing of cancer cells within the whole electric field, in contrast to EChT, which is limited to areas nearby electrodes. Remarkable tumor destruction efficacy is further demonstrated in this in vivo EDT treatment with PtNPs. Therefore, this study presents a new type of cancer therapy strategy with a tumor‐killing mechanism different from existing methods, using nanoparticles with electrocatalytic functions. This EDT method appears to be minimally invasive, and is able to offer homogeneous killing effects to the entire tumor with a relatively large size.

The efficacy of the conventional photodynamic therapy (PDT) is markedly suppressed by limited penetration depth of light in biological tissues and oxygen depletion in the hypoxic tumor microenvironment. Herein, mesoporous silica nanospheres with fine CaF:Yb,Er upconversion nanocrystals entrapped in their porous structure are synthesized via a thermal decomposition method. After subsequently coating with a thin MnO layer and loading with a photosensitizer, Chlorin e6 (Ce6), a new type of nanoscale PDT platform is obtained. Within such composite nanoparticles, Mn ions doped into the lattice of CaF crystals effectively enhance the near-infrared (NIR)-triggered red-light upconversion photoluminescence for exciting the adsorbed Ce6 via resonance energy transfer, enabling the improved photodynamic phenomenon. Meanwhile, the MnO coating modulates the hypoxic tumor microenvironment by in situ generating O through the reaction with tumor endogenous HO. Both mechanisms acting synchronously lead to the superior therapeutic outcome in NIR-triggered photodynamic tumor therapy.

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Daunting challenges in investigating the controlled release of drugs in complicated intracellular microenvironments demand the development of stimuli-responsive drug delivery systems. Here, a nanoparticle system, CaF2:Tm,Yb@mSiO2, made of a mesoporous silica (mSiO2) nanosphere with CaF2:Tm,Yb upconversion nanoparticles (UCNPs) is developed, filling its mesopores and with its surface-modified with polyacrylic acid for binding the anticancer drug molecules (doxorubicin, DOX). The unique design of CaF2:Tm,Yb@mSiO2 enables us to trigger the drug release by two mechanisms. One is the pH-triggered mechanism, where drug molecules are preferentially released from the nanoparticles at acidic conditions unique for the intracellular environment of cancer cells compared to normal cells. Another is the 808 nm near infrared (NIR)-triggered mechanism, where 808 nm NIR induces the heating of the nanoparticles to weaken the electrostatic interaction between drug molecules and nanoparticles. In addition, luminescence resonance energy transfer occurs from the UCNPs (the energy donor) to the DOX drug (the energy acceptor) in the presence of 980 nm NIR irradiation, allowing us to monitor the drug release by detecting the vanishing blue emission from the UCNPs. This study demonstrates a new multifunctional nanosystem for dual-triggered and optically monitored drug delivery, which will facilitate the rational design of personalized cancer therapy.