Photodynamic therapy (PDT) is a clinically approved anti-cancer treatment that involves the activation of an otherwise inactive sensitiser drug with light, which in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS). As oxygen is a key requirement for the generation of ROS in PDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using PDT can be a challenge. In this manuscript, we have prepared a CaO₂ nanoparticle (NP) formulation coated with a pH-sensitive polymer to enable the controlled generation of molecular oxygen as a function of pH. The polymer coat was designed to protect the particles from decomposition while in circulation but enable their activation at lower pH values in hypoxic regions of solid tumours. The oxygen generating capability of the polymer coated NPs was demonstrated in aqueous solution with minimal oxygen produced at pH 7.4, whereas it increased significantly when the pH was reduced to 6.2. The polymer coated CaO₂ NPs were also observed to significantly increase tumour pO₂ levels (p < 0.05) in mice bearing ectopic human xenograft MIA PaCa-2 pancreatic tumours with an average increase in tumour pO₂ of 6.5 mm Hg in the period 10–30 min following administration. A statistically significant improvement in PDT mediated efficacy (p < 0.001) was also observed when the particles were administered to mice bearing the same tumours 20 min prior to PDT treatment. These results suggest that the polymer coated CaO₂ NP formulation offers significant potential as an in situ method for oxygen generation to enhance the efficacy of treatments that depend on the presence of oxygen to elicit a cytotoxic effect.

光动力疗法（PDT）是一种临床认可的抗癌疗法，涉及用光激活原本没有活性的敏化剂药物，该药物在分子氧存在下会产生细胞毒性活性氧（ROS）。由于氧气是PDT中产生ROS的关键要求，并且鉴于缺氧是大多数实体癌肿瘤的特征，因此使用PDT治疗缺氧肿瘤可能是一个挑战。在本手稿中，我们准备了CaO ₂纳米颗粒（NP）制剂涂有对pH敏感的聚合物，能够根据pH来控制分子氧的产生。聚合物涂层的设计可防止颗粒在循环中分解，但可使其在较低的pH值下在实体瘤的低氧区域中活化。在水溶液中在pH 7.4时产生的氧气最少，证明了聚合物包被的NP的氧气产生能力，而当pH值降至6.2时，氧气的产生能力显着增加。还观察到聚合物包被的CaO ₂ NPs显着增加了 异位人类异种移植MIA PaCa-2胰腺肿瘤小鼠的肿瘤pO ₂水平（p <0.05），平均肿瘤pO ₂增加在给药后的10-30分钟内，汞含量为6.5毫米汞柱。 当在PDT治疗前20分钟将颗粒给药于患有相同肿瘤的小鼠时，还观察到PDT介导的功效有统计学上的显着改善（p <0.001）。这些结果表明，聚合物包被的CaO ₂ NP制剂作为产生氧的原位方法提供了巨大的潜力，以增强依赖于氧的存在来引起细胞毒性作用的治疗的功效。