4.8 Article

ROS-Responsive Nanocomplex of aPD-L1 and Cabazitaxel Improves Intratumor Delivery and Potentiates Radiation-Mediated Antitumor Immunity

Journal

NANO LETTERS
Volume -, Issue -, Pages -

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.2c03227

Keywords

ROS-responsive; PD-L1; cabazitaxel; tumor penetration; antitumor immunity

Funding

  1. National Natural Science Foundation of China
  2. Shandong Province Natural Science Foundation
  3. International Partnership Program of Chinese Academy of Sciences
  4. [32071385]
  5. [32271461]
  6. [32130058]
  7. [31930066]
  8. [ZR2019ZD25]
  9. [153631KYSB20190013]

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This study developed a ROS-responsive albumin nanocomplex that enhanced T cell activation and reduced immunosuppressive cells, resulting in significant inhibition of tumor growth in breast and colon tumor models. The nanocomplex offers a promising platform for effective cancer immunotherapy with enhanced intratumor delivery capacity.
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 enhance-ment in CD3+CD8+ T cells and the interferon (IFN)-gamma-expressing subtype, respectively, and notably reduced versatile immunosup-pressive 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.

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