Design of Cyclic Peptide-Based Nanospheres and the Delivery of siRNA

Abstract

In recent years, cyclic peptides have attracted much attention due to their chemical and enzymatic stability, low toxicity, and easy modification. In general, the self-assembled nanostructures of cyclic peptides tend to form nanotubes in a cyclic stacking manner through hydrogen bonding. However, studies exploring other assembly strategies are scarce. In this context, we proposed a new assembly strategy based on cyclic peptides with covalent self-assembly. Here, cyclic peptide-(DPDPDP) was rationally designed and used as a building block to construct new assemblies. With cyclo-(DP)3 as the structural unit and 2,2′-diamino-N-methyldiethylamine as the linker, positively charged nanospheres ((CP)6NS) based on cyclo-(DP)3 were successfully constructed by covalent self-assembly. We assessed their size and morphology by scanning electron microscopy (SEM), TEM, and DLS. (CP)6NS were found to have a strong positive charge, so they could bind to siRNA through electrostatic interactions. Confocal microscopy analysis and cell viability assays showed that (CP)6NS had high cellular internalization efficiency and low cytotoxicity. More importantly, real-time polymerase chain reaction (PCR) and flow cytometry analyses indicated that (CP)6NS-siRNA complexes potently inhibited gene expression and promoted tumor cell apoptosis. These results suggest that (CP)6NS may be a potential siRNA carrier for gene therapy.

Multicomponent Peptide-Based Hydrogels Containing Chemical Functional Groups as Innovative Platforms for Biotechnological Applications

“…In recent years, many different materials such as nanofibers [1,2], nanotubes [3,4], nanospheres [5,6],and hydrogels (HGs) [7,8] have attracted increasing interest as suitable and innovative platforms for biomedical and pharmaceutical applications [9][10][11], including tissue engineering [12,13] and the delivery of drugs [14,15] or diagnostic agents [16,17]. Hydrogels are three-dimensional macroscopic networks able to retain large amounts of water or other biological fluids [18].…”

pH‐responsive albumin‐mimetic synthetic nanoprobes for magnetic resonance/fluorescence imaging of thyroid cancer

“…The results of the flow apoptosis assay showed that MnO 2 @BSA‐Cy5.5 induced apoptosis rates of 8.56% and 7.21% in Nthy‐ori3‐1 and 8305C cells, respectively, which were not significantly different from the PBS‐treated groups (Figure 4C). As shown in (Figure 4B), the hemolysis rate was only 3.23% in the highest concentration of 200 μg/mL of MnO 2 @BSA‐Cy5.5, which was lower than the 5% that could induce hemolytic effect 18 . Cytotoxicity and hemolysis assays showed that our prepared MnO 2 @BSA‐Cy5.5 have good biosafety and can be further used for in vivo studies.…”

“…As shown in (Figure 4B), the hemolysis rate was only 3.23% in the highest concentration of 200 μg/mL of MnO 2 @BSA-Cy5.5, which was lower than the 5% that could induce hemolytic effect. 18 Cytotoxicity and hemolysis assays showed that our prepared MnO 2 @BSA-Cy5.5 have good biosafety and can be further used for in vivo studies.…”

Porous protein crystals: synthesis and applications

“…35 While this system is restricted to small-length peptides, the resulting scaffold shares the characteristic tunability of LPCs via amino acid substitutions, as evidenced by changes in molar uptake of Nile red in response to substitutions at the pore-facing residues. 35 Similarly, cyclic peptide nanotubes (cPNTs) have received increasing attention in recent years for a number of applications, particularly for therapeutic delivery, 36,37 owing to their high biocompatibility and ease of synthesis. Similar to LPCs, cPNTs can be synthesized with a range of pore sizes, 38,39 in some cases as high as 2 μm in diameter.…”