Department of Nuclear Medicine, Northern Jiangsu People's Hospital, Clinical Medical College, Yangzhou University, Yangzhou 225001, China; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China.
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China.
Biomater Adv. 2024 Oct;163:213962. doi: 10.1016/j.bioadv.2024.213962. Epub 2024 Jul 19.
Solid tumors create a hypoxic microenvironment and this character can be utilized for cancer therapy, but the hypoxia levels are insufficient to achieve satisfactory therapeutic benefits. Some tactics have been used to improve hypoxia, which however will cause side effects due to the uncontrolled drug release. We herein report near-infrared (NIR) photoactivatable three-in-one nanoagents (PCT) to aggravate tumor hypoxia and enable amplified photo-combinational chemotherapy. PCT are formed based on a thermal-responsive liposome nanoparticle containing three therapeutic agents: a hypoxia responsive prodrug tirapazamine (TPZ) for chemotherapy, a vascular targeting agent combretastatin A-4 (CA4) for vascular disturbance and a semiconducting polymer for both photodynamic therapy (PDT) and photothermal therapy (PTT). With NIR laser irradiation, PCT generate heat for PTT and destructing thermal-responsive liposomes to achieve activatable releases of TPZ and CA4. Moreover, PCT produce singlet oxygen (O) for PDT via consuming tumor oxygen. CA4 can disturb the blood vessels in tumor microenvironment to aggravate the hypoxic microenvironment, which results in the activation of TPZ for amplified chemotherapy. PCT thus enable PTT, PDT and hypoxia-amplified chemotherapy to afford a high therapeutic efficacy to almost absolutely eradicate subcutaneous 4 T1 tumors and effectively inhibit tumor metastases in lung and liver. This work presents an activatable three-in-one therapeutic nanoplatform with remotely controllable and efficient therapeutic actions to treat cancer.
实体瘤会产生缺氧的微环境，这种特性可被用于癌症治疗，但缺氧水平不足以达到令人满意的治疗效果。一些策略已经被用于改善缺氧，但由于药物释放不受控制，会引起副作用。我们在此报告近红外（NIR）光激活的三合一纳米制剂（PCT），以加重肿瘤缺氧并实现放大的光组合化疗。PCT 基于含有三种治疗剂的热响应脂质体纳米颗粒形成：用于化疗的缺氧反应性前药替拉扎胺（TPZ）、用于血管干扰的血管靶向剂康普瑞汀 A-4（CA4）和用于光动力疗法（PDT）和光热疗法（PTT）的半导体聚合物。用近红外激光照射，PCT 产生 PTT 的热量并破坏热响应脂质体，以实现 TPZ 和 CA4 的激活释放。此外，PCT 通过消耗肿瘤氧产生用于 PDT 的单线态氧（O）。CA4 可扰乱肿瘤微环境中的血管，加重缺氧微环境，从而激活 TPZ 以增强化疗效果。PCT 因此能够进行 PTT、PDT 和缺氧增强化疗，以极高的治疗效果几乎完全根除皮下 4T1 肿瘤，并有效抑制肺和肝中的肿瘤转移。这项工作提出了一种具有远程可控和高效治疗作用的可激活三合一治疗纳米平台，用于治疗癌症。
