The effect of phospho-peptide on the stability of gold nanoparticles and drug delivery

Abstract

Background Gold nanoparticles (AuNPs) have been proposed for many applications in medicine and bioanalysis. For use in all these applications, maintaining the stability of AuNPs in solution by suppressing aggregation is paramount. Herein, the effects of amino acids were investigated in stabilizing AuNPs by rationally designed peptide scaffolds. Results Compared to other tested amino acids, phosphotyrosine (pY) significantly stabilized AuNPs. Our results indicated that pY modified AuNPs presented a high level of stability in various solutions, and had good biocompatibility. When a pY-peptide was used in stabilizing AuNPs, the phosphate group could be removed by phosphatases, which subsequently caused the aggregation and the cargo release of AuNPs. In vitro study showed that AuNPs formed aggregation in a phosphatase concentration depending manner. The aggregation of AuNPs was well correlated with the enzymatic activity (R 2 = 0.994). In many types of cancer, a significant increase in phosphatases has been observed. Herein, we demonstrated that cancer cells treated with pY modified AuNPs in conjunction with doxorubicin killed SGC-7901 cells with high efficiency, indicating that the pY peptide stabilized AuNPs could be used as carriers for targeted drug delivery. Conclusion In summary, pY peptides can act to stabilize AuNPs in various solutions. In addition, the aggregation of pY-AuNPs could be tuned by phosphatase. These results provide a basis for pY-AuNPs acting as potential drug carriers and anticancer efficacy. Electronic supplementary material The online version of this article (10.1186/s12951-019-0522-y) contains supplementary material, which is available to authorized users.

<p>A Review on the Synthesis and Functionalization of Gold Nanoparticles as a Drug Delivery Vehicle</p>

“…Nanoparticles have also been conjugated with peptide/ amino acid in order to produce effective and targeted delivery systems. Synthesis of AuNPs conjugated with aspartic acid, 14 glutamic acid, phenylalanine and tryptophan, 202 L-cysteine, 203 lysine, 204 and peptides 15,205 has been reported. Amino acids and peptides bind with negatively charged AuNPs through amine groups, whereas the negatively charged carboxylic groups extend outwards to stabilize AuNPs.…”

“…The results have shown that phospho-tyrosine modified AuNPs when used as a delivery vehicle for doxorubicin were more effective at killing SGC-7901 cells. 205 Another study reports the conjugation of peptide CALNN and its derivative CALNNR8 with AuNPs for targeting components present inside the cell. AuNPs with the size of 30 nm could cross the cell membrane more easily through the processes of endocytosis and micropinocytosis.…”

Methods for Reducing the Toxicity of Metal and Metal Oxide NPs as Biomedicine

“…When pY peptide was used to stabilize Au NPs, the phosphate group could be removed with phosphatase, which then aggregated and released the Au NP charge. A significant increase in phosphatase has been observed in many types of cancer, indicating that aggregation of nanoparticles can be regulated by phosphatase [55]. It was also noted that by modifying the gold surface with polyethylene glycol modified with thiol groups, high efficiency was confirmed in the protection of Au NPs, in particular against the release of gold while allowing the binding of a large amount of drug and testing them as a carrier [56].…”

Hierarchical drug release designed Au @PDA-PEG-MTX NPs for targeted delivery to breast cancer with combined photothermal-chemotherapy

“…Interestingly, AuNPs have attracted great attention during the past decade owing to their facile synthesis and surface functionalization [ 12 ], along with high photothermal conversion capacity in the near infrared region (NIR) without harmful side effects in biological systems [ 13 – 15 ]. AuNPs can be used in NIR imaging of tumors, as they possess good photostability [ 16 ].…”