Brain Tumor Cell Membrane‐Coated Lanthanide‐Doped Nanoparticles for NIR‐IIb Luminescence Imaging and Surgical Navigation of Glioma

Abstract

Intraoperative visualization of the full extent of brain tumor by luminescence imaging helps to improve the degree and accuracy of brain tumor resection, thereby prolonging the survival of patients. However, the limited imaging depth and spatial resolution and the poor blood‐brain barrier (BBB) permeability of most currently available luminescent probes restrict the imaging performance and surgical resection efficiency of brain tumor. Here, a brain tumor cell membrane‐coated lanthanide‐doped nanoparticles (CC‐LnNPs) in the near‐infrared‐IIb window (NIR‐IIb, 1500–1700 nm) is designed for brain tumor imaging and surgical navigation. The coating of brain tumor cell membrane endows CC‐LnNPs with immune escape, BBB crossing, and homotypic targeting abilities, which are inherited from the source brain tumor cells. In addition, compared with clinically approved imaging agent indocyanine green, CC‐LnNPs present higher temporal and spatial resolution, higher stability, and lower background signals, enabling clear visualization of the brain tumor boundary. With the guidance of NIR‐IIb fluorescence, the glioma tissue (size < 3 mm, depth > 3 mm) could be clearly visualized and completely removed as a proof of concept. This study offers new insight for the future design of nanoprobe to image brain tumor and to achieve precise diagnosis and surgical navigation of brain tumor.

Cell-Membrane-Coated Nanoparticles for Targeted Drug Delivery to the Brain for the Treatment of Neurological Diseases

“…However, there are drawbacks associated with this property, which limits its application to cancer cell membranes. Currently, it is known that cancer-cell-membrane-coated nanoparticles are used on gliomas and metastases, as is detailed in Table 2 [ 80 , 81 , 82 , 85 , 86 , 87 , 88 , 89 , 90 ].…”

“…This may cause toxic damage to healthy tissues [ 37 ]. Many studies have shown that the most vulnerable sites for the accumulation of CMCNPs after their entry into blood circulation are the lesions, liver, lung, and spleen; however, CMCNPs do not cause damage to these tissues [ 28 , 33 , 34 , 35 , 36 , 37 , 57 , 58 , 59 , 80 , 87 , 90 ]. In addition, in most reports about CMCNPs, the toxicity testing of CMCNPs in vitro and vivo showed that the cytotoxicity and systemic toxicity of CMCNPs were negligible [ 29 , 34 , 36 , 54 , 81 , 90 ].…”

“…Many studies have shown that the most vulnerable sites for the accumulation of CMCNPs after their entry into blood circulation are the lesions, liver, lung, and spleen; however, CMCNPs do not cause damage to these tissues [ 28 , 33 , 34 , 35 , 36 , 37 , 57 , 58 , 59 , 80 , 87 , 90 ]. In addition, in most reports about CMCNPs, the toxicity testing of CMCNPs in vitro and vivo showed that the cytotoxicity and systemic toxicity of CMCNPs were negligible [ 29 , 34 , 36 , 54 , 81 , 90 ]. Using MPM@P NGs to treat C6 cells and bEnd.3 cells, respectively, the results showed that the cytotoxic ability of the MPM@P NGs for C6 cells was much higher than that of the bEnd.3 cells [ 36 ], illustrating that MPM@P NGs were less toxic to normal cells.…”

Recent advances in NIR-II fluorescence based theranostic approaches for glioma

“…This method is comparable with T2-weighted MRI and can probably be used for intraoperative visualization. To improve the BBB permeability, Liu et al coated a brain tumor cell membrane with Er-based lanthanide doped nanoparticles to form an NIR-IIb fluorescence imaging agent that targets glioma ( Wang et al, 2022b ). This nanoparticle, NaYbF 4 :Gd,Er,Ce@NaYF 4 , has a diameter of approximately 50 nm and is capable of coating human glioblastoma cell membrane vesicles after modification with phosphatidylcholine to increase the water dispersibility.…”

Biomimetic nanoparticles for tumor immunotherapy

“…Western blot analysis can only distinguish between the composition of modified and original membranes. Fifth, it is whether the activity of cell membrane is difficult to assess after modification ( Wang et al, 2022a ). Although gold nanoparticle antibody labeling can identify the direction of membrane coating, the process is complicated.…”