"Beyond the Knife"-Applying Theranostic Technologies to Enhance Outcomes in Neurosurgical Oncology

Abstract

The current standard of care for brain tumor management includes maximal safe surgical resection followed by concurrent chemotherapy and radiation therapy. Recent advances in image-guided surgical techniques have enhanced the precision of tumor resections, yet there remains a critical need for innovative technologies to further improve patient outcomes. Techniques such as fluorescence image-guided neurosurgery in combination with stereotactic radiosurgery have improved outcomes for patients with brain tumors. In this article for Brain Science's Special Issue Recent Advances in Translational Neuro-Oncology, we review the use of image-guided neurosurgery and stereotactic radiosurgery for the treatment of brain tumors. In addition, we summarize the emerging use of theranostic nanoparticles for the delivery of diagnostic and therapeutic technologies to enable the neurosurgeon to perform more precise surgical resections in the operating room, to specifically target the delivery of existing and novel treatments to tumor cells, and to augment the efficacy of stereotactic radiosurgery. These innovative translational tools will allow neurosurgeons, neuro-oncologists, and radiation oncologists to go "beyond the knife" to improve the survival of brain tumor patients.

Keywords: Cyberknife; blood–brain barrier; brain tumors; chemotherapy; fluorescence-guided surgery; gliomas; image-guided surgery; nanotechnology; neuro-oncology; neurosurgery; radiosurgery.

Figure 1

The current standard of care for the treatment of brain tumors. Modern-day treatment of primary and metastatic brain tumors includes: (A) maximal safe surgical resection; (B) adjuvant stereotactic radiosurgery and/or radiotherapy to the surrounding tumor bed and remaining tumor burden; and (C) systemic chemotherapy, targeted therapies, or immunotherapies.

Figure 2

Representative example of fluorescence-guided brain tumor surgery. Preoperative (A) axial, (B) coronal, and (C) sagittal contrast-enhanced T1-weighted magnetic resonance images (MRIs) of a patient with a right frontal glioma. Intraoperative (D) white light, and (E) 5-ALA fluorescence images of the glioma tumor before resection. Postresection (F) white light and (G) 5-ALA images of the resection cavity. Postoperative (H) axial, (I) coronal, and (J) sagittal contrast-enhanced T1-weighted MRIs showing maximal safe surgical resection of the glioma. White dashed lines indicated the margins of the tumor.

Figure 3

Examples of brain tumor targeting theranostic nanotechnologies. (A) Liposomal nanoparticles or (B) filamentous phage nanoparticles can be functionalized with surface ligands (i.e., transferrin or chlorotoxin) that recognize (C) receptors expressed on the surface of brain tumors (i.e., transferrin receptor, MMP1/2 receptors, and voltage-gated Ca²⁺ channels) for tumor-specific targeting. The conjugation of fluorescent dyes (i.e., ICG) on the surface of the nanoparticles can aid in intraoperative detection of tumor tissue. The packaging of therapies (i.e., chemotherapies, gene therapies) in the nanoparticles allows for concurrent treatment delivery.

Figure 4

Leveraging theranostic nanotechnologies to compliment the treatment of brain tumors. (A) Current modalities used for treating brain tumors. (B) Theranostic nanoparticles can potentially augment these treatment modalities. Tools to enhance the delivery of nanoparticles across the blood brain barrier such as: (C) Focussed ultrasound, and (D) Enhanced convection delivery, can allow for tumor-targed delivery of novel combination therapies to increase tumor cell killing.