Cascade-Responsive 2-DG Nanocapsules Encapsulate aV-siCPT1C Conjugates to Inhibit Glioblastoma through Multiple Inhibition of Energy Metabolism

Zhang, Yongkang1,2; Ren, Yanhong1,2; Xu, Haoyue1,2; Li, Linfeng1,2; Qian, Feng1,2,4; Wang, Lansheng1; Quan, Ankang1; Ma, Hongwei1; Yu, Rutong1,2; Liu, Hongmei1,3

2023-02-01

10.1021/acsami.2c19285

ACS Applied Materials & Interfaces   Impact Factor & Quartile

1944-8244

1944-8252

Aerobic glycolysis is the primary energy supply mode for glioblastoma (GBM) cells to maintain growth and proliferation. However, due to the metabolic reprogramming of tumor cells, GBM can still produce energy through fatty acid oxidation (FAO) and amino acid metabolism after blocking this metabolic pathway. In addition, GBM can provide a steady stream of nutrients through high-density neovascularization, which puts the block energy metabolism therapy for glioma in the situation of "internal and external problems". Herein, based on the abundant reactive oxygen species (ROS) and glutathione (GSH) in the tumor microenvironment and cytoplasm, we successfully designed and developed a cascade-responsive 2-DG nanocapsule delivery system. This nanocapsule contains a conjugate of anti-VEGFR2 monoclonal antibody (aV) and CPT1C siRNA (siCPT1C) linked by a disulfide cross-linker (aV-siCPT1C). The surface of this nanocapsule (2-DG/aV-siCPT1C NC) is loaded with the glycolysis inhibitor 2-DG, and it utilizes GLUT1, which is highly expressed on the blood-brain barrier (BBB) and GBM cells, to effectively penetrate the BBB and target GBM. The nanocapsule realizes multidrug codelivery, jointly blocks glycolysis and FAO of GBM, and reduces angiogenesis. Meanwhile, it also solves the problems of low delivery efficiency of mAb in the central nervous system (CNS) and easy degradation of siRNA. In general, this drug joint delivery strategy could open up a new avenue for the treatment of GBM.

glioblastoma energy metabolism nanocapsule 2-DG siCPT1C VEGFR2

SCI

English

Corresponding

National Natural Science Foundation of China[82072796] ; Social Development Project of Jiangsu Department of Science and Technology[BE2020642] ; Postgraduate Research & Practice Innovation Program of Jiangsu Province["KYCX21_2657","KYCX22_2950"] ; Xuzhou Key RD Plan["KC22103","KC22242"]

Science & Technology - Other Topics ; Materials Science

Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000935732900001

AMER CHEMICAL SOC

Web of Science

1.Xuzhou Med Univ, Inst Nervous Syst Dis, Xuzhou 221002, Peoples R China
2.Xuzhou Med Univ, Dept Neurosurg, Affiliated Hosp, Xuzhou 221002, Peoples R China
3.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen 518055, Peoples R China
4.First Peoples Hosp Changzhou, Dept Neurosurg, Changzhou 213003, Jiangsu, Peoples R China

Zhang, Yongkang,Ren, Yanhong,Xu, Haoyue,et al. Cascade-Responsive 2-DG Nanocapsules Encapsulate aV-siCPT1C Conjugates to Inhibit Glioblastoma through Multiple Inhibition of Energy Metabolism[J]. ACS Applied Materials & Interfaces,2023.

Zhang, Yongkang.,Ren, Yanhong.,Xu, Haoyue.,Li, Linfeng.,Qian, Feng.,...&Liu, Hongmei.(2023).Cascade-Responsive 2-DG Nanocapsules Encapsulate aV-siCPT1C Conjugates to Inhibit Glioblastoma through Multiple Inhibition of Energy Metabolism.ACS Applied Materials & Interfaces.

Zhang, Yongkang,et al."Cascade-Responsive 2-DG Nanocapsules Encapsulate aV-siCPT1C Conjugates to Inhibit Glioblastoma through Multiple Inhibition of Energy Metabolism".ACS Applied Materials & Interfaces (2023).