A ROS-responsive synergistic delivery system for combined immunotherapy and chemotherapy

Doudou Hu; Wei Zhang; Jiajia Xiang; Dongdong Li; Yong Chen; Pengcheng Yuan; Shiqun Shao; Zhuxian Zhou; Youqing Shen; Jianbin Tang

doi:10.1016/j.mtbio.2022.100284

A ROS-responsive synergistic delivery system for combined immunotherapy and chemotherapy

Mater Today Bio. 2022 May 11:14:100284. doi: 10.1016/j.mtbio.2022.100284. eCollection 2022 Mar.

Authors

Doudou Hu^{1

2

3}, Wei Zhang^{1

4

2}, Jiajia Xiang^{1

4

2}, Dongdong Li^{1

4

2}, Yong Chen^{1

4

2}, Pengcheng Yuan^{1

4

2}, Shiqun Shao^{1

4

2}, Zhuxian Zhou^{1

4

2}, Youqing Shen^{1

4

2}, Jianbin Tang^{1

4

2}

Affiliations

¹ Zhejiang Key Laboratory of Smart BioMaterials and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.
² Key Laboratory of Biomass Chemical Engineering of the Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.
³ Subtropical Sericulture and Mulberry Resources Protection and Safety Engineering Research Center, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
⁴ ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou, 311215, China.

Abstract

Immune checkpoint blockade (ICB) therapies that target programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway are currently used for the treatment of various cancer types. However, low response rates of ICB remain the major issue and limit their applications in clinic. Here, we developed a ROS-responsive synergistic delivery system (pep-PAPM@PTX) by integrating physically-encapsulated paclitaxel (PTX) and surface-modified anti-PD-L1 peptide (pep) for combined chemotherapy and ICB therapy. Pep-PAPM@PTX could bind the cell surface PD-L1 and drive its recycling to lysosomal degradation, thus reverting PTX-induced PD-L1 upregulation and downregulating PD-L1 expression. As a result, pep-PAPM@PTX significantly promoted T cell infiltration and increased tumor immunoactivating factors, synergizing PTX chemotherapy to achieve enhanced anticancer potency in a triple-negative breast cancer (TNBC) model.

Keywords: Combination therapy; Immune checkpoint blockade; Immunotherapy; ROS-Responsive; Synergistic effect.