Multifunctional nanoparticles for brain tumor imaging and therapy

Abstract

Brain tumors are a diverse group of neoplasms that often carry a poor prognosis for patients. Despite tremendous efforts to develop diagnostic tools and therapeutic avenues, the treatment of brain tumors remains a formidable challenge in the field of neuro-oncology. Physiological barriers including the blood-brain barrier result in insufficient accumulation of therapeutic agents at the site of a tumor, preventing adequate destruction of malignant cells. Furthermore, there is a need for improvements in brain tumor imaging to allow for better characterization and delineation of tumors, visualization of malignant tissue during surgery, and tracking of response to chemotherapy and radiotherapy. Multifunctional nanoparticles offer the potential to improve upon many of these issues and may lead to breakthroughs in brain tumor management. In this review, we discuss the diagnostic and therapeutic applications of nanoparticles for brain tumors with an emphasis on innovative approaches in tumor targeting, tumor imaging, and therapeutic agent delivery. Clinically feasible nanoparticle administration strategies for brain tumor patients are also examined. Furthermore, we address the barriers towards clinical implementation of multifunctional nanoparticles in the context of brain tumor management.

Keywords: Brain tumor; Diagnosis; Drug delivery; Imaging; Nanoparticles; Nanotechnology; Theranostics; Therapy.

Figure 1

Transportation mechanisms of multifunctional nanoparticles into the brain tumor. (A) Transport of multifunctional nanoparticles across the BBB: 1) receptor-mediated transcytosis, 2) receptor-mediated endocytosis, 3) adsorptive-mediated transcytosis of nanoparticles with cationized ligands. (B) Mechanisms of transportation across the disrupted BBB and selective targeting of brain tumor cells: 1) passive targeting via the EPR effect, 2) adsorptive-mediated endocytosis or 3) receptor-mediated endocytosis. Both mechanisms offer a targeted delivery to brain cancer cells, sparing the normal tissue. NP: nanoparticle.

Figure 2

Triple-modality MRI-Photoacoustic-Raman nanoparticles (MPRs). MPRs were injected intravenously into mice bearing an orthotopic brain tumor (top). The proposed clinical use is diagramed at the bottom of the illustration. Detectability of MPRs by MRI allowed for preoperative detection and surgical planning. Photoacoustic imaging, with its relatively high resolution and deep tissue penetration, was then able to guide bulk tumor resection intraoperatively. Raman imaging, with its high sensitivity and spatial resolution, can then be used to remove any residual microscopic tumor burden. The resected specimen can subsequently be examined using a Raman probe ex vivo to verify clear tumor margins. Reproduced with permission from Ref .

Figure 3

Schematic structure of different nanocarriers (liposomes, polymeric nanoparticles including nanospheres and nanocapsules, dendrimers, and micelles) for drug delivery to the brain tumor. Reproduced with permission from Ref .