State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China.
Department of Imaging, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China.
Adv Mater. 2024 Jan;36(4):e2305243. doi: 10.1002/adma.202305243. Epub 2023 Dec 4.
Photodynamic therapy (PDT), which utilizes type I photoreactions, has great potential as an effective cancer treatment because of its hypoxia-tolerant superiority over the commonly used type II pathway. A few type I photosensitizers are exploited; however, they majorly induce cytotoxicity and possess poor tumor specificity and low-efficient theranostics. To resolve this issue, herein an aminopeptidase N (APN)-activated type I phototheranostic probe (CyA) is reported for anti-hypoxic PDT in conjunction with immunotherapy for effective cancer treatment. CyA can specifically activate near-infrared fluorescence, photoacoustic signals, and phototoxicity following APN-induced substrate cleavage and the subsequent generation of active phototheranostic molecules (such as CyBr). CyA endows specific imaging capabilities and effective phototoxicity toward tumor cells overexpressing APN under both normoxia and hypoxia. In addition, the locally activatable PDT induces systemic antitumor immune responses. More importantly, the integration of localized activated PDT and systemic immunotherapy evokes enhanced therapeutic effects with improved tumor inhibition efficiency in live mice compared with individual treatments. This study aims to present an activatable phototheranostic probe for effective hypoxia-tolerant PDT and combination therapy.
光动力疗法（PDT）利用 I 型光反应，由于其对缺氧的耐受性优于常用的 II 型途径，因此具有作为有效癌症治疗方法的巨大潜力。已经开发了一些 I 型光敏剂；然而，它们主要诱导细胞毒性，并且具有较差的肿瘤特异性和低效率的治疗诊断。为了解决这个问题，本文报道了一种氨肽酶 N（APN）激活的 I 型光热治疗探针（CyA），用于结合免疫疗法进行抗缺氧 PDT，以有效治疗癌症。CyA 可以在 APN 诱导的底物切割和随后产生的活性光治疗分子（如 CyBr）后特异性激活近红外荧光、光声信号和光毒性。CyA 赋予了在常氧和缺氧条件下过表达 APN 的肿瘤细胞特异性成像能力和有效的光毒性。此外，局部激活的 PDT 诱导全身性抗肿瘤免疫反应。更重要的是，与单独治疗相比，局部激活 PDT 和全身免疫治疗的整合在活体小鼠中引发了增强的治疗效果，提高了肿瘤抑制效率。本研究旨在提出一种用于有效耐缺氧 PDT 和联合治疗的可激活光治疗探针。
