A nitric-oxide driven chemotactic nanomotor for enhanced immunotherapy of glioblastoma

Abstract

The major challenges of immunotherapy for glioblastoma are that drugs cannot target tumor sites accurately and properly activate complex immune responses. Herein, we design and prepare a kind of chemotactic nanomotor loaded with brain endothelial cell targeting agent angiopep-2 and anti-tumor drug (Lonidamine modified with mitochondrial targeting agent triphenylphosphine, TLND). Reactive oxygen species and inducible nitric oxide synthase (ROS/iNOS), which are specifically highly expressed in glioblastoma microenvironment, are used as chemoattractants to induce the chemotactic behavior of the nanomotors. We propose a precise targeting strategy of brain endothelial cells-tumor cells-mitochondria. Results verified that the released NO and TLND can regulate the immune circulation through multiple steps to enhance the effect of immunotherapy, including triggering the immunogenic cell death of tumor, inducing dendritic cells to mature, promoting cytotoxic T cells infiltration, and regulating tumor microenvironment. Moreover, this treatment strategy can form an effective immune memory effect to prevent tumor metastasis and recurrence.

Biomimetic Macrophage Membrane-Camouflaged Nanoparticles Induce Ferroptosis by Promoting Mitochondrial Damage in Glioblastoma

“…Angiopep-2 (Ang) can specifically bind to the lipoprotein receptor-related protein 1 (LRP1) receptor, enhance the transport efficiency of NP across the BBB, and deliver drugs to the glioma. − In addition, the overexpression of α4 or β1 integrin on the surface of macrophages can bind vascular cell adhesion molecule-1 (VCAM-1), promote the penetration of the BBB and target gliomas . To assess the ability of Ang-MMsaNPs to permeate the BBB, an in vitro model was established with Transwell inserts placed in 24-well plates.…”

Covalent Organic Framework‐Based Nanomotor for Multimodal Cancer Photo‐Theranostics

“…The results depicted in Figure 4B,C demonstrate that the tumor volume was partially suppressed in the PDT ( 5) and PTT (6) treated groups compared to those of control groups (1)(2)(3)(4). This suggested that mPPy@COF-Por could partially eradicate tumor cells under single light irradiation.…”

“…Synthetic nanomotors, which can convert various energy sources into mechanical motion to achieve complex tasks in solution, have gained more and more attention [1,2] Compared with chemical and enzyme-powered nanomotors, [3,4] physical nanomotors driven by external fields, such as magnetic, ultrasound, light, and electric fields, offer more advantages for biomedical applications. For example, they are not limited by the availability of DOI: 10.1002/adhm.202301645 external chemical fuels (e.g., hydrogen peroxide (H 2 O 2 ), urea, or glucose).…”

Light-driven micro/nanomotors in biomedical applications

“…For example, Wan et al constructed a nitric oxide (NO)-driven nanomotor (Ang-PAMSe), which could effectively penetrate the BBB for glioblastoma treatment. 135 Therefore, MNMs that can actively move and target drug delivery are hopeful to provide a new solution for crossing the BBB.…”