Self-Assembling Peptide of d-Amino Acids Boosts Selectivity and Antitumor Efficacy of 10-Hydroxycamptothecin

Abstract

D-peptides, which consist of D-amino acids and can resist the hydrolysis catalyzed by endogenous peptidases, are one of the promising candidates for construction of peptide materials with enhanced biostability in vivo. In this paper, we report on a self-assembling supramolecular nanostructure of D-amino acid-based peptide Nap-G(D)F(D)F(D)YGRGD (D-fiber, (D)F meant D-phenylalanine, (D)Y meant D-tyrosine), which were used as carriers for 10-hydroxycamptothecin (HCPT). Transmission electron microscopy observations demonstrated the filamentous morphology of the HCPT-loaded peptides (d-fiber-HCPT). The better selectivity and antitumor activity of D-fiber-HCPT than L-fiber-HCPT were found in the in vitro and in vivo antitumor studies. These results highlight that this model D-fiber system holds great promise as vehicles of hydrophobic drugs for cancer therapy.

Gd(III)-induced Supramolecular Hydrogelation with Enhanced Magnetic Resonance Performance for Enzyme Detection

“…1A). Similar to many self-assembling peptide molecules that can form supramolecular nanostructures, the driving force of the self-assembly of the Nap-GFFYGRGD is hydrogen bond between peptide chain and π -π interaction between aromatic groups on Nap and amino acid of F. The peptide Nap-GFFYGRGD could self-assemble into supramolecular nanofibers but not hydrogels at the concentrations lower than 0.7 wt% in 4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES, pH = 7.4) solution44. The reason for the peptide incapable of forming hydrogels at these concentrations was the weak inter-fiber interaction and repulsion between negatively charged fibers.…”

The Unexpected Advantages of Using D-Amino Acids for Peptide Self- Assembly into Nanostructured Hydrogels for Medicine

“…The rise of self-assembling peptide nanostructures [2] and hydrogels has brought innovation to various medicinal fields [3], spanning from adaptive [4], biodegradable tissue engineering scaffolds [5] for wound healing and cell encapsulation, to unprecedented paradigms in drug delivery, and even targeted cell therapy [6]. Among the many peptide-based systems, low-molecular-weight gelators deserve special mention as they possess an economic advantage over longer peptides or more complex peptide-based derivatives [7].…”

D-amino acid-containing supramolecular nanofibers for potential cancer therapeutics

“…Recently, Yang and co-workers systematically studied the in vivo stability, distribution, and toxicity of the peptide nanofibers of peptides made of L- or D-amino acids (i.e., enantiomers 1 and 2 ) [82, 94]. Using hydroxycamptothecin (HCPT) as a model drug, they have shown the better selectivity and antitumor efficiency of the nanofibers containing D-amino acids versus L-amino acids.…”