A biomimetic targeted nanosystem delivering synergistic inhibitors for glioblastoma immune microenvironment reprogramming and treatment

Yulei Mu; Zhen Zhang; Huiqun Zhou; Min Jin; Liang Ma; Bangheng Liu; Cheng Ma; Xu Hu; Yi Zhang; Dong-An Wang

doi:10.1016/j.mtbio.2024.101222

A biomimetic targeted nanosystem delivering synergistic inhibitors for glioblastoma immune microenvironment reprogramming and treatment

Mater Today Bio. 2024 Sep 1:28:101222. doi: 10.1016/j.mtbio.2024.101222. eCollection 2024 Oct.

Authors

Yulei Mu¹, Zhen Zhang¹, Huiqun Zhou^{1

2}, Min Jin^{1

2}, Liang Ma¹, Bangheng Liu^{1

2}, Cheng Ma^{1

2}, Xu Hu¹, Yi Zhang³, Dong-An Wang^{1

2

4}

Affiliations

¹ Department of Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong.
² Karolinska Institutet Ming Wai Lau Centre for Reparative Medicine, HKSTP, Sha Tin, Hong Kong.
³ School of Integrated Circuit Science and Engineering, University of Electronic Science and Engineering of China, Chengdu, Sichuan, China.
⁴ Shenzhen Research Institute, City University of Hong Kong, Shenzhen, China.

Abstract

Efficient drug delivery across the blood-brain barrier is imperative for treating glioblastoma (GBM). This study utilized the GBM cell membrane to construct a biomimetic targeted nanosystem (GMNPs@AMD/RAPA) that hierarchically releases the CXCR4 antagonist AMD3100 and the mTOR pathway inhibitor rapamycin (RAPA) for reprogramming the tumor immune microenvironment and suppressing the progression of GBM. By initially inhibiting the CXCL12/CXCR4 axis, the tumor microenvironment (TME) was reprogrammed to enhance the infiltration of cytotoxic T lymphocytes (CTLs) into the TME while suppressing tumor cell survival, proliferation, and angiogenesis. Subsequently, through further cellular uptake and degradation of the nanoparticles, the mTOR pathway inhibitor RAPA was released, further suppressing the tumor progression. This study successfully combined chemotherapy and immunotherapy, achieving effective synergistic therapeutic effects, and suppressing the progression of GBM.

Keywords: Blood-brain barrier; CXCL12/CXCR4 axis; Glioblastoma; Small-molecule inhibitors; mTOR pathways.