Dendrimers as Powerful Building Blocks in Central Nervous System Disease: Headed for Successful Nanomedicine

Abstract

Dendrimers have emerged as a powerful class of nanomaterials in the nanomedicine field due to their unique structural features: globular, welldefined, highly branched and controllable structure, nanosizescale, low polydispersity, and the presence of several terminal groups that can be functionalized with different ligands simulating the multivalency present in different biological systems. Although in its infancy, the application of dendrimers as therapeutics or theranostic tools in central nervous system (CNS) disorders is already significant and has opened promising avenues in the treatment of many conditions where the inherent "smartness" of the dendritic structures is being explored to effectively target the CNS. Here we present an overview of the past and future challenges of the use of dendrimers to respond to one of the ultimate challenges in the (nano)medicine field: to attain CNS repair and regeneration.

Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA

“…Three regions (low, medium and high spot count) were defined based on the worst performing copolymer (hsD). The region for medium spot count was defined as mean spot count for hsD (3.5) ± Version: Postprint (identical content as published paper) This is a self-archived document from i3S -Instituto de Investigação e Inovação em Saúde in the University of Porto Open Repository For Open Access to more of our publications, please visit http://repositorio-aberto.up.pt/ A01/00 its corresponding standard deviation (2). The low spot count region is below 3.5 -2 and the high spot region is above 3.5 + 2.…”

“…Dendritic nanostructures are considered promising vehicles for different bioactive molecules due to their globular, well defined and highly branched structure, low polydispersity and tunable size. [1][2][3][4][5] The presence of chemical handles on the dendritic periphery further allows their functionalization with ligands in a specific and controlled manner to mimic the multivalency present in many biological systems. Particularly relevant is their capacity to complex and protect nucleic acids (NA) in compact nanostructures, coined " dendriplexes " (dendrimer-NA complexes), with application as non-viral vectors in gene therapy.…”

PAMAM dendrimers: blood-brain barrier transport and neuronal uptake after focal brain ischemia

“…Efforts to use neuroprotectants have emerged [5] but their success is limited by the reduced amounts that reach the lesion as well as by the lack of cell specificity. Both of these drawbacks can be overcome by the use of delivery vectors, such as dendrimers [6] and hyperbranched polymers (HBP) [7]. These can prolong the blood circulation half-life of the candidate molecule [7,8] and can be functionalized to have cell targeting specificity [6,7,9] increasing the amount that reaches the brain.…”

“…Both of these drawbacks can be overcome by the use of delivery vectors, such as dendrimers [6] and hyperbranched polymers (HBP) [7]. These can prolong the blood circulation half-life of the candidate molecule [7,8] and can be functionalized to have cell targeting specificity [6,7,9] increasing the amount that reaches the brain. Within the nanomedicine field, these vectors have emerged as interesting carriers due to their structural features, such as their globular and highly branched nanostructure, and the presence of several terminal functional groups that can be explored to tether, in a specific manner, different ligands and/or drugs.…”

“…Among the earliest proposed dendrimers, poly(amide amine) (PAMAM) [15] has been the most explored dendrimer for different applications due to their commercial availability [6]. However, one concern over the use of PAMAM in biological applications is their potential toxicity, especially in their cationic (amine-terminated) variant [ [16], [17], [18]].…”