Preoperative Detection and Intraoperative Visualization of Brain Tumors for More Precise Surgery: A New Dual-Modality MRI and NIR Nanoprobe

Abstract

In clinical practice, it is difficult to identify tumor margins during brain surgery due to its inherent infiltrative character. Herein, a unique dual-modality nanoprobe (Gd-DOTA-Ag2S QDs, referred as Gd-Ag2S nanoprobe) is reported, which integrates advantages of the deep tissue penetration of enhanced magnetic resonance (MR) imaging of Gd and the high signal-to-noise ratio and high spatiotemporal resolution of fluorescence imaging in the second near-infrared window (NIR-II) of Ag2S quantum dots (QDs). Due to the abundant tumor angiogenesis and the enhanced permeability and retention effect in the tumor, a brain tumor (U87MG) in a mouse model is clearly delineated in situ with the help of the Gd assisted T1 MR imaging and the intraoperative resection of the tumor is precisely accomplished under the guidance of NIR-II fluorescence imaging of Ag2S QDs after intravenous injection of Gd-Ag2S nanoprobe. Additionally, no histologic changes are observed in the main organs of the mouse after administration of Gd-Ag2S nanoprobe for 1 month, indicating the high biocompatibility of the nanoprobe. We expect that such a novel "Detection and Operation" strategy based on Gd-Ag2S nanoprobe is promising in future clinical applications.

Targeted Nanotherapies for the Treatment of Surgical Diseases

“…We discussed examples that are applicable across multiple fields of surgery as well as direct applicability to specific surgical diseases. Several therapies currently in development in animal models will influence neurosurgery, either by improving delivery of chemotherapeutics in a targeted fashion across the blood brain barrier, 33, 54, 58 or acting as a targeted therapy for cerebral hemorrhage. 41, 47 There are numerous therapeutics that will influence oncologic resection in the fields of surgical oncology, 36 breast cancer, urology, 43, 46 and otolaryngology 35 with therapeutics in development to directly target those types of tumors, potentially reducing the need for large surgical resections.…”

“…This technology has great potential to assist surgeons in achieving precise surgical margins during excision. 58 Overall, the application of targeted nanotherapies to imaging has the potential to improve our ability to detect disease and more precisely localize it, both preoperatively and intraoperatively.…”

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma

“…Gd-DOTA-Ag 2 S QDs were used to image the gliomas by diffusion, but they lacked specific targeting ability and led to low specificity and efficacy. 19 A QD-labeled aptamer GBI-10, which can specially bind to tenascin-C, was used as a nanoprobe for imaging glioma cell lines in vitro. 47 However, due to poor specificity and lack of verification in vivo, its clinical application was limited.…”

“…[16][17][18] Moreover, coating the NPs with PEG enable them to avoid clearance by reticuloendothelial system and plasma protein adsorption, and thus prolong the blood circulation of NPs in the body, and finally raise their probability of reaching their target tissue. [19][20][21] Gliomas always generate genetic rearrangements and mutations. 22 Comprehensive genomic analysis of GBM has identified that the amplification of EGFR gene is the most frequent genetic alteration associated with GBM.…”

Near-Infrared Illumination of Native Tissues for Image-Guided Surgery

“…1–3 Neglecting to carefully navigate the surgical field can lead to poor patient prognosis even morbidity. 4–11 Endocrine and exocrine tissues regulate the body’s hormone levels, and any perturbation, especially transection, can jeopardize the patient’s ability to recover after surgery and maintain proper hormone levels.…”