免疫光动力疗法（IPDT）已成为一种新的癌症治疗方式。新型光敏剂可以帮助实现 IPDT 固有的承诺，即完全根除肿瘤而不复发。我们在此报告了一种小分子光敏剂缀合物 LuCXB。该 IPDT 试剂将塞来昔布（环氧合酶 2 抑制剂）部分与近红外吸收镥泰克萨菲林光催化核心相结合。在水性环境中，LuCXB 的两种成分通过推断的供体-受体相互作用进行自关联。这种分子内缔合的结果是，在 730 nm 光照射下，LuCXB 通过 I 型光动力途径产生超氧自由基 (O2-·)；这提供了对抗肿瘤的第一道防线，同时促进了 IPDT。对于体内治疗应用，我们制备了一种靶向 CD133、适配体功能化的外泌体纳米光敏剂 (Ex-apt@LuCXB)，旨在靶向癌症干细胞。 Ex-apt@LuCXB 表现出良好的光敏性、可接受的生物相容性和强大的肿瘤靶向性。在光照射条件下，Ex-apt@LuCXB 可以放大 IPDT，同时在肝癌和乳腺癌小鼠模型中发挥显着的抗肿瘤作用。观察到的治疗效果归因于抗血管生成和光诱导癌症免疫疗法相结合的协同机制。

Immuno-photodynamic therapy (IPDT) has emerged as a new modality for cancer treatment. Novel photosensitizers can help achieve the promise inherent in IPDT, namely, the complete eradication of a tumor without recurrence. We report here a small molecule photosensitizer conjugate, LuCXB. This IPDT agent integrates a celecoxib (cyclooxygenase-2 inhibitor) moiety with a near-infrared absorbing lutetium texaphyrin photocatalytic core. In aqueous environments, the two components of LuCXB are self-associated through inferred donor-acceptor interactions. A consequence of this intramolecular association is that upon photoirradiation with 730 nm light, LuCXB produces superoxide radicals (O2-•) via a type I photodynamic pathway; this provides a first line of defense against the tumor while promoting IPDT. For in vivo therapeutic applications, we prepared a CD133-targeting, aptamer-functionalized exosome-based nanophotosensitizer (Ex-apt@LuCXB) designed to target cancer stem cells. Ex-apt@LuCXB was found to display good photosensitivity, acceptable biocompatibility, and robust tumor targetability. Under conditions of photoirradiation, Ex-apt@LuCXB acts to amplify IPDT while exerting a significant antitumor effect in both liver and breast cancer mouse models. The observed therapeutic effects are attributed to a synergistic mechanism that combines antiangiogenesis and photoinduced cancer immunotherapy.