Tunable synthesis of self-assembled cyclic peptide nanotubes and nanoparticles

Abstract

While tremendous efforts have been made in investigating scalable approaches for fabricating nanoparticles, less progress has been made in scalable synthesis of cyclic peptide nanoparticles and nanotubes, despite their great potential for broader biomedical applications. In this paper, tunable synthesis of self-assembled cyclic peptide nanotubes and nanoparticles using three different methods, phase equilibrium, pH-driven, and pH-sensitive methods, were proposed and investigated. The goal is scalable nanomanufacturing of cyclic peptide nanoparticles and nanotubes with different sizes in large quality by controlling multiple process parameters. Cyclo-(L-Gln-D-Ala-L-Glu-D-Ala-)2 was applied to illustrate the proposed ideas. In the study, mass spectrometry and high performance liquid chromatography were employed to verify the chemical structures and purity of the cyclic peptides. Morphology and size of the synthesized nanomaterials were characterized using atomic force microscopy and dynamic light scattering. The dimensions of the self-assembled nanostructures were found to be strongly influenced by the cyclic peptide concentration, side chain modification, pH values, reaction time, stirring intensity, and sonication time. This paper proposed an overall strategy to integrate all the parameters to achieve optimal synthesis outputs. Mechanisms of the self-assembly of the cyclic peptide nanotubes and nanoparticles under variable conditions and tunable parameters were discussed. This study contributes to scalable nanomanufacturing of cyclic peptide based self-assembled nanoparticles and nanotubes for broader biomedical applications.

Application of nanodiagnostics in point-of-care tests for infectious diseases

“…[16][17][18] For the past several decades, biomedical applications including tissue engineering, drug delivery, bioimaging, and nanodiagnostics have been promoted by the nanotechnology significantly. [19][20][21][22] Among these applications, nanodiagnostics have drawn more and more attention for the infectious diseases because of their unique characteristics in early detection, high sensitivity, and the potential for POCT. 15 Toward this direction, lots of novel and efficient nanodiagnostics for infectious diseases have been developed.…”

Peptide Self-Assembled Nanostructures for Drug Delivery Applications

“…For instance, the internal diameter of the cyclic peptide could increase from 2Å to 13Å after increasing the peptide length from 4 to 12 amino acids [2,66]. Moreover, the eight-residue cyclic peptides with the sequence of cyclo-(L-Gln-D-Ala-L-Glu-DAla) 2 can not only self-assemble into nanotube structures, but also self-assemble into nanoparticles with different methods and self-assembly parameters shown in Figure 4 [18].…”

“…For example, pH values are very important for peptides with charged amino acids such as Glu, Asp, Lys, His, and Arg. The status of these peptides with negative or positive surface charges could be sensitively affected by the pH values and then self-assembled into different nanostructures [18]. Tunable management of the physical and biological properties of peptide self-assembled nanostructures is highly desired for their successful utilization in drug delivery applications.…”

“…Many self-assembling systems have been developed for various biomedical applications; peptide self-assembled nanostructures remain one of the most promising directions for many reasons [18]. They are easily fabricated using solid-phase peptide methods where the peptide sequence could be specifically modified at molecular levels [19].…”

Additive nanomanufacturing of lab-on-a-chip fluorescent peptide nanoparticle arrays for Alzheimer’s disease diagnosis

“…The designed peptides will be first synthesized, cyclized and purified for the on-chip self-assembly. In our previous studies, considerable progress has been made in the tunable synthesis of self-assembled peptide nanoparticles using multiple strategies, including phase equilibrium, pH-driven, and pH-sensitive approaches [37]. In this research, the peptide sequence will be utilized for three functions: ordered self-assembly, fluorescence property and recognition to particular AD biomarkers inside human serum.…”