Dendritic architectures based on bis-MPA: functional polymeric scaffolds for application-driven research

Abstract

Dendritic polymers are highly branched, globular architectures with multiple representations of functional groups. These nanoscale organic frameworks continue to fascinate researchers worldwide and are today under intensive investigation in application-driven research. A large number of potential application areas have been suggested for dendritic polymers, including theranostics, biosensors, optics, adhesives and coatings. The transition from potential to real applications is strongly dictated by their commercial accessibility, scaffolding ability as well as biocompatibility. A dendritic family that fulfills these requirements is based on the 2,2-bismethylolpropionic acid (bis-MPA) monomer. This critical review is the first of its kind to cover most of the research activities generated on aliphatic polyester dendritic architectures based on bis-MPA. It is apparent that these scaffolds will continue to be in the forefront of cutting-edge research as their structural variations are endless including dendrons, dendrimers, hyperbranched polymers, dendritic-linear hybrids and their hybridization with inorganic surfaces.

Synthesis and NMR characterization of dendrimers based on 2, 2-bis-(hydroxymethyl)-propanoic acid (bis-HMPA) containing peripheral amino acid residues for gene transfection

“…As monomer of AB 2 type to build the hydrolyzable dendrimeric architecture we chose the 2,2-bis(hydroxymethyl)propanoic acid (bis-HMPA), a known building block used to prepare an ample variety of dendrimeric scaffolds 37 and we adopted the synthetic strategy known as double-stage convergent approach 37,40 as previously described in another our paper accepted for publication on Macromolecular Research and currently in print. This strategy required the synthesis of a fourth generation acetonide-protected dendron starting from bis-HMPA, its reaction with a tris-hydroxyl core molecule and final removal of the acetonide protection to obtain the fourth generation dendrimer having 48 peripheral hydroxyl groups (G4OH, 10).…”

“…10 On this ground, with the aim of preparing hydrolyzable dendrimer structures which were, at the same time, adequately protonated but also well tolerated by the cells and which could harmonize transfection capacity with a low level of toxicity, we report in this work versatile chemical protocols for the synthesis of a library of 15 dendrimers of fourth, fifth and sixth generation derived from 2,2-bis(hydroxymethyl)propanoic acid (bis-HMPA), a monomer of the AB 2 type used to prepare a variety of dendritic architectures. 37 The prepared dendrimers have an internal polyester structure known for its biocompatibility 38 and contain at the surface a set of amino acid residues, natural or not, alone or in combination which can be protonated at physiological pH thus making dendrimers able to bind DNA, to enter into the cells and to escape the endosomal compartment as soon as possible to avoid degradation.…”

Self-assembling amphiphilic Janus dendrimers: mesomorphic properties and aggregation in water

“…Bis-MPA based dendrimers exhibit excellent aqueous solubility and are easy to fabricate via convergent or divergent methods. They have proven to be perfectly suitable 70 to build drug carriers [27][28] thanks to their low cytotoxicity and biodegradability. The Janus dendrimers proposed in this article are formed by two bis-MPA dendritic blocks of different polarity (Chart 1).…”

Polyester Dendrimers: Smart Carriers for Drug Delivery

“…Higher generation polyester dendrimers can easily be prepared with facile synthesis of other dendrimers and a variety of methods have been reported for ester bond formation [126][127][128][129][130][131][132][133][134][135]. The synthesis of polyester dendrimers in general [135] and those derived from bis-2,2-hydroxymethylpropanoic acid (bis-HMPA) in particular [58] have been reviewed. A recent attractive strategy is the use of uronium-based coupling agents, TBTU [136], TATU [137], and COMU [138] to promote ester bond formation between carboxylic acid dendrons and polyalcoholic cores [139].…”

“…The success of dendritic nanoparticles for drug delivery applications largely depends on the ability of scientists to design smart carriers with the ability to overcome drug leakage, immunogenicity, cytotoxicity, reticuloendothelial system uptake, and hemolytic toxicity among other shortcomings. One strategy to overcome these shortcomings is to use polyester dendrimers which have been shown to be non-toxic and biocompatible [19,[56][57][58][59][60]. By attaching a drug to a suitable carrier, it is possible to enhance its aqueous solubility, increase its circulation half-life, target certain tissues, improve drug transit across biological barriers, and slow drug metabolism [61][62][63][64][65][66].…”