光动力疗法
单线态氧
光敏剂
氧气
活性氧
体内
药理学
化学
癌细胞
血红蛋白
癌症
癌症研究
生物物理学
医学
光化学
生物
生物化学
内科学
有机化学
生物技术
作者
Tian Xu,Yuying Ma,Qinling Yuan,Hui‐Xin Hu,Xin‐Kai Hu,Zhiyu Qian,J Rolle,Yueqing Gu,Siwen Li
出处
期刊:ACS Nano
[American Chemical Society]
日期:2020-03-10
卷期号:14 (3): 3414-3425
被引量:242
标识
DOI:10.1021/acsnano.9b09426
摘要
Photodynamic therapy (PDT) combined with oxygenating strategies is widely employed in cancer treatment; however, oxygen-boosted PDT has failed to achieve an ideal effect due to the complexity, heterogeneity, and irreversible hypoxic environment generated by tumor tissues. With the emergence of Fe-dependent ferroptosis boasting reactive oxygen species (ROS) cytotoxicity as well, such a chemodynamic approach to cancer therapy has drawn extensive attention. In this study, hemoglobin (Hb) is connected with the photosensitizer chlorin e6 (Ce6) to construct a 2-in-1 nanoplatform (SRF@Hb-Ce6) with Sorafenib (SRF, ferroptosis promotor) loaded, combining oxygen-boosted PDT and potent ferroptosis. Benefiting from the intrinsic presence of Fe capable of binding oxygen, hemoglobin concurrently furnishes oxygen for oxygen-dependent PDT and Fe for Fe-dependent ferroptosis. Furthermore, amphiphilic MMP2-responsive peptide is incorporated into the skeleton of the nanoplatform to ensure drug-release specificity for safety improvement. Correlative measurements demonstrate the potentiation of PDT and ferroptosis with SRF@Hb-Ce6. More importantly, PDT strengthens ferroptosis by recruiting immune cells to secrete IFN-γ, which can sensitize the tumor to ferroptosis in our findings. The therapeutic effect of synergistic treatment with SRF@Hb-Ce6 in vitro and in vivo was proven significant, revealing the promising prospects of combined PDT and ferroptosis therapy with the 2-in-1 nanoplatform.
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