School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China.
Acta Biomater. 2021 Mar 1;122:354-364. doi: 10.1016/j.actbio.2020.12.036. Epub 2021 Jan 6.
The unfavorable factors in tumor microenvironment such as hypoxia and limited HO levels greatly impede the anticancer efficacy of chemotherapy and chemodynamic therapy (CDT). To address these issues and achieve O/HO-sufficient chemo/chemodynamic combination therapy, we synthesized a solid lipid monostearin coated calcium peroxide (CaO) nanocarrier for the co-delivery of a chemotherapeutic drug doxorubicin (DOX) and a biocompatible Fenton catalyst iron-oleate complex. Specifically, the solid lipid shells of nanoparticles could disintegrate in lipase-overexpressed cancer cells to release iron-oleate and expose CaO cores. Afterwards, the uncovered CaO responded to the acidic aqueous environment within cancer cells, leading to the release of DOX molecules and generation of HO. Based on Fenton reactions, Fe liberated from iron-oleate reacted with HO to produce O for hypoxia-relieved chemotherapy, and Fe for the catalytic generation of hydroxyl radical to initiate CDT. Both treatments synergistically contribute to the enhanced antitumor outcomes.
肿瘤微环境中的不利因素，如缺氧和有限的 HO 水平，极大地阻碍了化疗和化学动力学治疗（CDT）的抗癌疗效。为了解决这些问题并实现 O/HO 充足的化疗/化学动力学联合治疗，我们合成了一种固体脂质单硬脂酸钙包裹过氧化钙（CaO）纳米载体，用于共递送化疗药物阿霉素（DOX）和生物相容性芬顿催化剂油酸铁复合物。具体来说，纳米颗粒的固体脂质外壳可以在过表达脂肪酶的癌细胞中分解，释放出油酸铁并暴露出 CaO 核。之后，暴露的 CaO 会对癌细胞内的酸性水环境做出响应，导致 DOX 分子的释放和 HO 的生成。基于芬顿反应，从油酸铁中释放的 Fe 与 HO 反应生成用于缓解缺氧的化疗的 O，以及用于引发 CDT 的羟基自由基的催化生成的 Fe。这两种治疗方法协同作用，增强了抗肿瘤效果。
