Dendrimer Technology in Glioma: Functional Design and Potential Applications

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.

Blood–brain barrier-crossing dendrimers for glioma theranostics

“…Nevertheless, conventional contrast agents have many problems such as short retention time, renal toxicity, and lack of specificity. 9 Functionalized dendrimers can be applied as targeted nanocarriers of imaging contrast agents to facilitate precision glioma diagnosis. 54,55 For example, Karki et al 53 prepared an MR and fluorescence imaging agent utilizing G5 PAMAM dendrimers to load clinically relevant Gd-DOTA and the near-infrared fluorescence dye DL680.…”

“…The recent progress in nanotechnology and nanomedicine holds great promise for the efficient treatment of glioma. 6,7 A range of nanoscale drug delivery systems including but not limited to inorganic nanomaterials, 8 dendrimers, 9 polymer nanoparticles (NPs), 10 liposomes, 11 micelles, 12 and nanogels 13,14 have been developed. These carriers can be used to encapsulate various kinds of therapeutic molecules and contrast agents such as small molecular drugs, proteins, peptides, genes, gold (Au) NPs, and so on, through physical or chemical interactions.…”