Engineering antimicrobial supramolecular polymer assemblies

Abstract

Antibacterial resistance against conventional antibiotics has emerged as a global health problem. To address this problem, antimicrobial peptides (AMPs) have been recognized as alternatives due to their fast‐killing activity and less propensity to induce resistance. Here, the AMPs are engineered via a supramolecular fashion to control and increase their biological performance. The AMPs are modified with ureido‐pyrimidinone (UPy) to obtain UPy‐AMP monomers, followed by modular self‐assembling to realize antibacterial UPy‐AMP supramolecular polymers. These positively charged assemblies are illustrated as stable, short fibrous or rod‐like UPy‐AMP nanostructures with enhanced antibacterial activity and modulable cytotoxicity. Moreover, these antibacterial UPy‐AMP assemblies can be internalized by both THP‐1 derived macrophages and human kidney cells, which would be an effective potential therapy to deliver the AMPs into mammalian cells to address intracellular infections. Overall, the results present here demonstrate that supramolecular engineering of AMPs provides a powerful tool to enhance the antibacterial activity, modulate cytotoxicity and accelerate the clinical application of AMPs.

The effect of charge and albumin on cellular uptake of supramolecular polymer nanostructures

“…2,[5][6][7] Additionally, targeting ligands, cell penetrating peptides and other functional molecules have been incorporated to achieve selectivity. 2,[5][6][7][8] Among these nanocarriers, various types of supramolecular nanostructures [9][10][11][12][13][14][15][16][17][18][19][20][21][22] have gained significant interest. These nanostructures are composed of tunable molecular recognition motifs which can self-assemble through dynamic and reversible non-covalent interactions.…”

Collagen type I mimicking peptide additives to functionalize synthetic supramolecular hydrogels

“…UPy-dimers self-assemble into 1D stacks, using π-π interactions stabilized by quadruple hydrogen bonding via a flanking urea group, which allows these stacks to turn into a bundle [ 34 , 36 , 42 , 43 ]. Conjugation of the synthesized peptides to a supramolecular UPy-moiety allows, due to the modularity of supramolecular materials, the formation of a stable bulk material functionalized with these peptide additives, acting as biochemical cues to induce cell adhesion, cell spreading, or even more complex cell-material interactions [ 35 , [37] , [38] , [39] , [40] , [41] , [44] , [45] , [46] , [47] , [48] , [49] ].…”

Bisurea‐Based Supramolecular Polymers for Tunable Biomaterials

“…[15] Functionalization with charged moieties or peptides resulted in supramolecular polymers which showed siRNA delivery, cellular adhesion and antimicrobial activity. [16][17][18] A similarly well-studied supramolecular building block is the benzene-1,3,5-tricarboxamide (BTA), which forms fiber-like structures in water. [19][20][21][22][23][24][25][26] Recently, peripheral functional groups have been introduced into the BTA-based systems via co-assembly with functional monomers.…”

“…By mixing mono‐ and bivalent UPy monomers, polymers with tunable dynamics can be obtained [15] . Functionalization with charged moieties or peptides resulted in supramolecular polymers which showed siRNA delivery, cellular adhesion and antimicrobial activity [16–18] . A similarly well‐studied supramolecular building block is the benzene‐1,3,5‐tricarboxamide (BTA), which forms fiber‐like structures in water [19–26] .…”