A Nanotherapeutic Agent for Synergistic Tumor Therapy: Co-Activation of Photochemical-Biological Effects

Single-mode photodynamic therapy (PDT) based on photochemical reactions is limited by the tumor microenvironment, which reduces the ablation efficiency for solid tumors. Making it vital to seek ways to improve the tumor therapeutic effect. Based on this, we propose a dual-mode intelligent nanotherapeutic system (HAP@BMPns) based on photochemical-biological effects. HAP@BMPns is composed of an acid-responsive high-calcium biomimetic nanomaterial (HAP) and photosensitizer (BMP), which can spontaneously activate photochemical (Type-I PDT) and biological effects for synergistic cancer therapy. HAP@BMPns breaks down upon entering tumor cells under acidic conditions, releasing a large amount of Ca²⁺ and BMP. Triggering intracellular Ca²⁺ overload, which induces mitochondrial damage, leading to apoptosis. Synchronously, Type-I PDT of BMP under two-photon (800 nm) laser irradiation becomes activated, resulting in enhanced destruction of tumor cells by the photochemical effect. Cell studies have indicated that HAP@BMPns (41.6 μg/mL) exhibits a strong inhibitory efficiency on tumor cells growth, with low (22.4 %) survival rate. However, the individual components, i. e. BMP (5.0 μM) and HAP (41.6 μg/mL) display low inhibitory efficiency with high survival rates (55.9 % and 63.0 % respectively). Therefore, this dual-mode synergistic treatment strategy using acid-triggered photochemical-biological effects significantly enhances the ablation of solid tumors, realizing the synergistic effect. We hope that this design strategy can provide guidance for the design and development of a tumor therapeutic platform.