A Selective Nanoblocker of Cellular Stress Response for Improved Drug-Free Tumor Therapy.

Nanotechnology-based drug-free therapeutic systems utilizing external stimuli can avoid the inherent side effects of drugs and become an attractive therapeutic strategy. However, the cellular stress responses (CSR) are activated encounter with external stimuli, which greatly weaken the efficacy of the drug-free antitumor. Thus, we proposed a CSR regulation strategy and synthesized the glucose oxidase (GOx)-modified Cu 3 BiS 3 nanosheets (CBSG NSs) encapsulated by calcium carbonate (CBSG@CaCO 3 ) as the novel drug-free nanoagent. The CBSG@CaCO 3 not only cause external stimuli such as energy consumption and oxidative stress damage, but also can destroy the CSR mechanism to guarantee optimal efficacy of starvation-chemodynamic therapy. In tumor cells, the CaCO 3 shell layer of CBSG@CaCO 3 is rapidly degraded, releasing the slowly degradable CBSG NSs with NIR-II photothermal propertie that accelerated the production of external stimuli under laser irradiation. Meanwhile, CaCO 3 can block CSR to disrupt the adaptive viability of cancer cells by inhibiting expresstion of P27 and NRF2. Importantly, the CSR regulation achieves selective treatment on tumor cells based on the difference in physiological conditions between cancer cells and normal cells. This drug-free cancer therapy with selectivity improves the problem of poor efficacy under the action of CSR, which offers a new avenue in the cancer-related disease treatment. This article is protected by copyright. All rights reserved.