Dendrimer Technology in Glioma: Functional Design and Potential Applications

SIMPLE SUMMARY: Gliomas are common primary brain tumors that account for a high number of cancer-related deaths worldwide. Patients with aggressive gliomas have poor prognoses due to resistance to current treatment regimens. Anatomical barriers between the brain and the peripheral circulation make glioma drug delivery particularly challenging. Recently, the potential for dendrimers—nanomaterials characterized by a unique branching structure with many binding sites—to deliver therapeutic and diagnostic cargo directly to the site of gliomas has been explored. An increasing number of studies in glioma cell lines and animal models suggest that this dendrimer-based delivery approach may serve to decrease drug toxicity and allow for the use of nontraditional therapeutic and imaging agents in glioma. Here, we review the physical characteristics of dendrimers, strategies for modifying dendrimers to target glioma cells, and novel applications of this nanotechnology in glioma models. ABSTRACT: Novel therapeutic and diagnostic methods are sorely needed for gliomas, which contribute yearly to hundreds of thousands of cancer deaths worldwide. Despite the outpouring of research efforts and funding aimed at improving clinical outcomes for patients with glioma, the prognosis for high-grade glioma, and especially glioblastoma, remains dire. One of the greatest obstacles to improving treatment efficacy and destroying cancer cells is the safe delivery of chemotherapeutic drugs and biologics to the tumor site at a high enough dose to be effective. Over the past few decades, a burst of research has leveraged nanotechnology to overcome this obstacle. There has been a renewed interest in adapting previously understudied dendrimer nanocarriers for this task. Dendrimers are small, highly modifiable, branched structures featuring binding sites for a variety of drugs and ligands. Recent studies have demonstrated the potential for dendrimers and dendrimer conjugates to effectively shuttle therapeutic cargo to the correct tumor location, permeate the tumor, and promote apoptosis of tumor cells while minimizing systemic toxicity and damage to surrounding healthy brain tissue. This review provides a primer on the properties of dendrimers; outlines the mechanisms by which they can target delivery of substances to the site of brain pathology; and delves into current trends in the application of dendrimers to drug and gene delivery, and diagnostic imaging, in glioma. Finally, future directions for translating these in vitro and in vivo findings to the clinic are discussed.