Energy‐Free, Singlet Oxygen‐Based Chemodynamic Therapy for Selective Tumor Treatment without Dark Toxicity

Abstract Traditional singlet oxygen‐based antitumor therapies have been burdened with the necessity of external energy (e.g., light and ultrasound) and harmful dark toxicity. Ascorbate at the pharmacological concentration could accumulate hydrogen peroxide only in the tumor site. It is postulated that the concurrent delivery of ascorbate and nanoparticulate hypochlorous ion (ClO − ) could produce singlet oxygen at the tumor site as an energy‐free, tumor‐specific therapy. The ClO − is loaded in a hybrid core–shell nanocarrier consisting of a zeolitic imidazolate framework and amphiphilic poloxamer 188. Intracellular singlet oxygen production is verified in 4T1 cells by the cooperation between hybrid nanocarriers and ascorbate, which induces significant apoptotic cell death. Upon intravenous nanocarriers delivery plus intraperitoneal ascorbate administration to xenograft mice, the in vivo antitumor efficacy of this cooperative nanomedicine is demonstrated without noticeable side‐effects. This work demonstrates a proof‐of‐concept of singlet oxygen‐based chemodynamic therapy for selective tumor eradication, which produces a novel trigger‐free, singlet oxygen‐based cancer therapy without the side effects of traditional photodynamic and sonodynamic therapy.