Yin Junjing, Cao Haiqiang, Wang Hong, Sun Kaoxiang, Li Yaping, Zhang Zhiwen
School of Pharmacy, Yantai University, Yantai 264005, China.
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Acta Pharm Sin B. 2020 Nov;10(11):2246-2257. doi: 10.1016/j.apsb.2020.06.004. Epub 2020 Jun 13.
Hypoxia is a serious impediment to current treatments of many malignant tumors. Catalase, an antioxidant enzyme, is capable of decomposing endogenous hydrogen peroxide (HO) into oxygen for tumor reoxygenation, but suffered from instability and limited delivery to deep interior hypoxic regions in tumor. Herein, a deep-penetrated nanocatalase-loading DiIC (5, DiD) and soravtansine (Cat@PDS) were provided by coating catalase nanoparticles with PEGylated phospholipids membrane, stimulating the structure and function of erythrocytes to relieve tumor hypoxia for enhanced chemo-photodynamic therapy. After intravenous administration, Cat@PDS preferentially accumulated at tumor sites, flexibly penetrated into the interior regions of tumor mass and remarkably relieved the hypoxic status in tumor. Notably, the Cat@PDS + laser treatment produced striking inhibition of tumor growth and resulted in a 97.2% suppression of lung metastasis. Thus, the phospholipids membrane-coated nanocatalase system represents an encouraging nanoplatform to relieve tumor hypoxia and synergize the chemo-photodynamic cancer therapy.
缺氧是当前许多恶性肿瘤治疗的严重障碍。过氧化氢酶作为一种抗氧化酶，能够将内源性过氧化氢（H₂O₂）分解为氧气，用于肿瘤再氧合，但存在稳定性差以及向肿瘤深部缺氧区域递送受限的问题。在此，通过用聚乙二醇化磷脂膜包裹过氧化氢酶纳米颗粒，构建了一种具有深度穿透能力的负载纳米过氧化氢酶的DiIC（5, DiD）和索拉非尼（Cat@PDS），模拟红细胞的结构和功能以缓解肿瘤缺氧，从而增强化学 - 光动力疗法。静脉注射后，Cat@PDS优先在肿瘤部位蓄积，能够灵活穿透到肿瘤块内部区域，并显著缓解肿瘤内的缺氧状态。值得注意的是，Cat@PDS + 激光治疗对肿瘤生长产生了显著抑制，导致肺转移抑制率达到97.2%。因此，磷脂膜包裹的纳米过氧化氢酶系统是一种令人鼓舞的纳米平台，可缓解肿瘤缺氧并协同化学 - 光动力癌症治疗。
