College of Polymer Science and Engineering, Sichuan University, Chengdu 610000, China.
Med-X Center for Materials, Sichuan University, Chengdu 610000, China.
Biomater Sci. 2024 Sep 25;12(19):5105-5114. doi: 10.1039/d4bm00712c.
Photodynamic therapy (PDT) has emerged as a promising treatment for malignant tumours in recent decades due to its impressive spatiotemporal selectivity, minimal invasiveness, and few adverse effects. Despite these advancements, there remain significant challenges in effectively delivering photosensitizers to tumours and overcoming tumour hypoxia to maximize the therapeutic benefits of PDT. Ongoing research efforts are focused on developing innovative strategies to overcome the above-mentioned challenges, such as nanoplatforms and combination therapy approaches. Hence, reactive oxygen species (ROS)-responsive polymeric micelles are promising candidates to enhance the distribution and retention of photosensitizers within tumours. Additionally, efforts to alleviate tumour hypoxia may further improve the anti-tumour effects of PDT. In this study, we designed ROS-responsive polymeric micelles (TC@PTP) co-loaded with a Tapp-COF, a porphyrin derivative, and capsaicin for PDT of melanoma. These ROS-responsive nanocarriers, constructed from thioketal (TK)-linked amphiphilic di-block copolymers (PEG5K-TK-PLGA5K), could accumulate in the tumor microenvironment and release drugs under the action of ROS. Capsaicin, acting as a biogenic respiratory inhibitor, suppressed mitochondrial respiration and the hypoxia-inducible factor 1 (HIF-1) signaling pathway, thereby increasing oxygen levels at the tumour site. These PDT-triggered ROS-responsive nanoparticles effectively alleviated the tumour hypoxic microenvironment and enhanced anti-tumour efficacy. With superior biocompatibility and tumour-targeting abilities, the platform holds great promise for advancing anti-tumour combination therapy.
光动力疗法（PDT）在近几十年来已成为治疗恶性肿瘤的一种有前途的方法，因为它具有令人印象深刻的时空选择性、最小的侵入性和很少的副作用。尽管取得了这些进展，但在有效将光敏剂递送到肿瘤部位并克服肿瘤缺氧以最大程度地提高 PDT 的治疗效果方面仍存在重大挑战。目前的研究工作集中在开发创新策略来克服上述挑战，例如纳米平台和联合治疗方法。因此，活性氧（ROS）响应性聚合物胶束是增强肿瘤内光敏剂分布和保留的有前途的候选物。此外，缓解肿瘤缺氧的努力可能会进一步提高 PDT 的抗肿瘤效果。在这项研究中，我们设计了 ROS 响应性聚合物胶束（TC@PTP），其共载有 Tapp-COF（一种卟啉衍生物）和辣椒素，用于黑色素瘤的 PDT。这些由硫代缩酮（TK）连接的两亲性二嵌段共聚物（PEG5K-TK-PLGA5K）构建的 ROS 响应性纳米载体可以在肿瘤微环境中积累，并在 ROS 的作用下释放药物。辣椒素作为生物呼吸抑制剂，抑制线粒体呼吸和缺氧诱导因子 1（HIF-1）信号通路，从而增加肿瘤部位的氧气水平。这些 PDT 触发的 ROS 响应性纳米粒子有效地缓解了肿瘤缺氧微环境并增强了抗肿瘤疗效。该平台具有优异的生物相容性和肿瘤靶向能力，有望推进抗肿瘤联合治疗。
