Crescent-Shaped Supramolecular Tetrapeptide Nanostructures

Abstract

Self-assembly of amphiphilic peptide-based building blocks gives rise to a plethora of interesting nanostructures such as ribbons, fibers, and tubes. However, it remains a great challenge to employ peptide self-assembly to directly produce nanostructures with lower symmetry than these highly symmetric motifs. We report here our discovery that persistent and regular crescent nanostructures with a diameter of 28 ± 3 nm formed from a series of tetrapeptides with the general structure AdK S K S EX (Ad = adamantyl group, K S = lysine residue functionalized with an S-aroylthiooxime (SATO) group, E = glutamic acid residue, and X = variable amino acid residue). In the presence of cysteine, the biological signaling gas hydrogen sulfide (H 2 S) was released from the SATO units of the crescent nanostructures, termed peptide− H 2 S donor conjugates (PHDCs), reducing levels of reactive oxygen species (ROS) in macrophage cells. Additional in vitro studies showed that the crescent nanostructures alleviated cytotoxicity induced by phorbol 12-myristate-13-acetate more effectively than common H 2 S donors and a PHDC of a similar chemical structure, AdK S K S E, that formed short nanoworms instead of nanocrescents. Cell internalization studies indicated that nanocrescent-forming PHDCs were more effective in reducing ROS levels in macrophages because they entered into and remained in cells better than nanoworms, highlighting how nanostructure morphology can affect bioactivity in drug delivery.

Emerging pro-drug and nano-drug strategies for gemcitabine-based cancer therapy

“…Polymeric nanoparticles we discuss here mainly refer to dendrimer, chitosan, albumin, which themselves are nanoscopic and thus can be used as drug carriers directly. As a result of narrowly distributed and nanoscopic structure, these polymeric nanoparticles can attain improved delivery efficiency and enhanced therapeutic efficiency of gemcitabine [75] , [76] , [77] , [78] .…”

Thiophosphopeptides Instantly Targeting Golgi Apparatus and Selectively Killing Cancer Cells

“…The formation of micelles of pS1 likely facilitates the cellular uptake by caveolin-mediated endocytosis, similar to the cellular uptake of peptide amphiphiles. [18][19][20][21] We first incubated HeLa cells with CellLight® Golgi-RFP 22 for 24 hours to transfect RFP at the Golgi, then incubated the HeLa cells with pS1 (10 M) for 8 minutes (Figure 1). The fluorescence from the assemblies of S1 overlaps with the red fluorescence from all Golgi-RFP, confirming that pS1 targets the Golgi of the HeLa cells.…”

Spatial and Temporal Modulation of Cell Instructive Cues in a Filamentous Supramolecular Biomaterial

“…Supramolecular polymers constructed from monomers that associate through non-covalent interactions, such as hydrogen-bonding, π-stacking, and hydrophobicity, provide access to filamentous structures that bear analogy to the biopolymers that compose the ECM. 32 , 33 For some monomers above a critical concentration in water, hydrogel materials can be formed that are mechanically weak with self-recovering character having advantages for numerous applications in the biomedical area. 34 , 35 To overcome their low stiffness, cross-linking of the supramolecular polymer filaments has been examined by introducing reactive groups on the monomers that can either ligate with themselves or through small molecules and polymers.…”