DataVXACS NanoPaper
journal article·2024-04-02

Blood–Brain Barrier Penetrating Nanovehicles for Interfering with Mitochondrial Electron Flow in Glioblastoma

Yulin Zhang, Kaiyan Xi, Yuying Zhang, Zezheng Fang, Yi Zhang, Kaijie Zhao, Fan Feng, Jianyu Shen, Mingrui Wang, Runlu Zhang, Bo Cheng, Huimin Geng, Xingang Li, Bin Huang, Kang-Nan Wang, Shilei Ni

ACS Nano· Volume 18· Issue 13
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Source abstract

Abstract

Glioblastoma multiforme (GBM) is the most aggressive and lethal form of human brain tumors. Dismantling the suppressed immune microenvironment is an effective therapeutic strategy against GBM; however, GBM does not respond to exogenous immunotherapeutic agents due to low immunogenicity. Manipulating the mitochondrial electron transport chain (ETC) elevates the immunogenicity of GBM, rendering previously immune-evasive tumors highly susceptible to immune surveillance, thereby enhancing tumor immune responsiveness and subsequently activating both innate and adaptive immunity. Here, we report a nanomedicine-based immunotherapeutic approach that targets the mitochondria in GBM cells by utilizing a Trojan-inspired nanovector (ABBPN) that can cross the blood-brain barrier. We propose that the synthetic photosensitizer IrPS can alter mitochondrial electron flow and concurrently interfere with mitochondrial antioxidative mechanisms by delivering si-OGG1 to GBM cells. Our synthesized ABBPN coloaded with IrPS and si-OGG1 (ISA) disrupts mitochondrial electron flow, which inhibits ATP production and induces mitochondrial DNA oxidation, thereby recruiting immune cells and endogenously activating intracranial antitumor immune responses. The results of our study indicate that strategies targeting the mitochondrial ETC have the potential to treat tumors with limited immunogenicity.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Mitochondrial Function and Pathology · ATP Synthase and ATPases Research · Nanoplatforms for cancer theranostics

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Road, Jinan 250012, Shandong, China

Jinan Microecological Biomedicine Shandong Laboratory and Shandong Key Laboratory of Brain Function Remodeling, Jinan 250117, Shandong, China

Department of Pediatrics, Qilu hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Road, Jinan 250012, Shandong, China

Department of Obstetrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, No. 247 Beiyuan Road, Jinan 250033, Shandong, China

Department of Radiation Oncology, Qilu hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Road, Jinan 250012, Shandong, China

State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, Shandong, China

Funding

China Postdoctoral Science Foundation · Taishan Scholar Foundation of Shandong Province · National Natural Science Foundation of China · Natural Science Foundation of Shandong Province · Jinan Science and Technology Bureau · Jinan Microecological Biomedicine Shandong Laboratory

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