Engineered Macrophage-Membrane-Coated Nanoparticles with Enhanced PD-1 Expression Induce Immunomodulation for a Synergistic and Targeted Antiglioblastoma Activity
- Tieying Yin*Tieying Yin*Email for T.Y.: [email protected]Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People’s Republic of ChinaMore by Tieying Yin,
- Qin FanQin FanSchool of Medicine, Chongqing University, Chongqing 400044, People’s Republic of ChinaMore by Qin Fan,
- Fangfang HuFangfang HuKey Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People’s Republic of ChinaMore by Fangfang Hu,
- Xiaoyue MaXiaoyue MaSchool of Medicine, Chongqing University, Chongqing 400044, People’s Republic of ChinaMore by Xiaoyue Ma,
- Ying YinYing YinSchool of Medicine, Chongqing University, Chongqing 400044, People’s Republic of ChinaMore by Ying Yin,
- Bingyi WangBingyi WangSchool of Medicine, Chongqing University, Chongqing 400044, People’s Republic of ChinaMore by Bingyi Wang,
- Lei KuangLei KuangSchool of Medicine, Chongqing University, Chongqing 400044, People’s Republic of ChinaMore by Lei Kuang,
- Xiaoye HuXiaoye HuSchool of Medicine, Chongqing University, Chongqing 400044, People’s Republic of ChinaMore by Xiaoye Hu,
- Bo XuBo XuSchool of Medicine, Chongqing University, Chongqing 400044, People’s Republic of ChinaMore by Bo Xu, and
- Yazhou Wang*Yazhou Wang*Email for Y.W.: [email protected]School of Medicine, Chongqing University, Chongqing 400044, People’s Republic of ChinaMore by Yazhou Wang
Abstract
Glioblastoma (GBM), the most common subtype of malignant gliomas, is characterized by aggressive infiltration, high malignancy, and poor prognosis. The frustrating anti-GBM outcome of conventional therapeutics is due to the immunosuppressive milieu, in addition to the formidable obstacle of the blood–brain barrier (BBB). Combination therapy with an immune checkpoint blockade (ICB) has emerged as a critical component in the treatment of GBM. Here, we report an engineered macrophage-membrane-coated nanoplatform with enhanced programmed cell death-1 (PD-1) expression ([email protected]/RAPA). Using both in vitro and in vivo GBM models, we demonstrate that [email protected]/RAPA can efficiently traverse across the BBB in response to the tumor microenvironment (TME) recruitment with nanoparticles accumulating at the tumor site. Furthermore, we show a boosted immune response as a result of enhancing CD8+ cytotoxic T-lymphocyte (CTL) infiltration. Together we provide a new nanoplatform for enhancing ICB in combination with conventional chemotherapy for GBM and many other cancers.
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