Triboelectric Immunotherapy/Calcium Electroporation System for Synergistically Enhanced Tumor Therapy

Abstract Calcium overload is a promising anticancer treatment that kills tumor cells primarily by causing mitochondrial dysfunction in cells. However, calcium overload therapy is limited by inefficient cellular uptake of Ca ²⁺ . Herein, a triboelectric immunotherapy/calcium electroporation (CaEP) synergistic tumor therapy is developed using electrostatic‐breakdown induced direct‐current (DC) generated by a triboelectric nanogenerator (TENG). In this work, an 8 × 10 cm TENG can generate approximately 5–30 pulsed DC with a peak output of 60 µA in a single sliding. The pulsed DC can not only directly damage tumor cells and activate T cells‐mediated adaptive immunity response to inhibit tumor growth (that is, triboelectric immunotherapy), but also promote the cellular uptake of Ca ²⁺ (increased up to 235.9% in vitro) by electroporation to improve the therapeutic effect of calcium overload tumor therapy. The triboelectric immunotherapy/CaEP treatment can increase IL‐12 and TNF‐α within the tumor tissue to 175.7% and 185.5%, respectively, illustrating the upregulation of immune‐promoting factor levels. Moreover, the adenosine triphosphate (ATP) leakage and high mobility group box 1 protein (HMGB1) release are also enhanced (increased to 211.2%, and 154.3%, respectively). This work offers an effective electrical‐assisted tumor therapy technique and provides proof of concept of this technique as a miniaturized tumor treatment system for solid tumors.