ROS-Responsive Nanocomplex of aPD-L1 and Cabazitaxel Improves Intratumor Delivery and Potentiates Radiation-Mediated Antitumor Immunity.
Jiaoying WangJie LiYao WuXiaoxuan XuXindi QianYing LeiHuanzhen LiuZhiwen ZhangYaping LiPublished in: Nano letters (2022)
Despite the promising benefits of immune checkpoint inhibitors (ICIs) in clinical cancer treatments, the therapeutic efficacy is largely restricted by low antitumor immunity and limited intratumor delivery in solid tumors. Herein, we designed a reactive oxygen species (ROS)-responsive albumin nanocomplex of antiprogrammed cell death receptor ligand 1 (aPD-L1) and cabazitaxel (RAN-PC), which exhibited prominent tumor accumulation and intratumor permeation in 4T1 tumors. Compared with the negative control, the RAN-PC + radiation treatment (RAN-PC+X) produced a 3.61- and 5.10-fold enhancement in CD3<sup>+</sup>CD8<sup>+</sup> T cells and the interferon (IFN)-γ-expressing subtype, respectively, and notably reduced versatile immunosuppressive cells. Moreover, RAN-PC+X treatment resulted in notable retardation of tumor growth, with a 78.97% inhibition in a 4T1 breast tumor model and a 90.30% suppression in a CT-26 colon tumor model. Therefore, the ROS-responsive albumin nanocomplex offers an encouraging platform for ICIs with prominent intratumor delivery capacity for cancer immunotherapy.
Keyphrases
- cell death
- reactive oxygen species
- cell cycle arrest
- dna damage
- cancer therapy
- induced apoptosis
- computed tomography
- high throughput
- immune response
- signaling pathway
- magnetic resonance imaging
- papillary thyroid
- oxidative stress
- combination therapy
- endoplasmic reticulum stress
- replacement therapy
- smoking cessation
- nk cells
- image quality