Synthesis of carboxylated gold nanoparticles for conjugation to anticancer peptide
,1 Morteza shourian
,2 Hassan mohabatkar
,3 Mohsen asghari
1. University of Isfahan
2. University of Guilan
3. University of Isfahan
4. University of Guilan
Nowadays, nanotechnology has great potential as a novel technique for precise diagnosis, early detection, and treatment of diseases. common nanomaterials are used as beneficial tools for targeting different types of therapeutic agents, including carbon nanotubes, quantum dots, liposomes, micelles, polymeric, graphene, gold nanoparticles (au nps), ferroferric oxide nanoparticles and so on. recently, among the various types of nanomaterials, the biomedical consumption of metallic nanoparticles, especially gold nanoparticles, has attracted a lot of attention because of their unique properties. these days, gold nanoparticles due to their nontoxicity, biocompatibility, ease of synthesis and surface functionalization have been chosen for different kinds of biomedical applications such as molecular imaging, drug carriers, biosensing, killers of cancer cells by hyperthermia treatment and etc. the conjugation of gold nps-drug in comparison to the free drug was shown to increase drug availability in circulation. on the other hand, most of the studies dedicated to cancer treatment have shown that angiogenesis plays an important role in the growth and metastasis of solid tumors. so treatments by anti-angiogenic agents is a widespread means of cancer treatment. one of the most important angiogenesis inducers is vascular endothelial growth factor (vegf). we have previously designed a peptide which competes with vegf and inhibits angiogenesis and thereby prevent tumor growth. in the present study, to increase the longevity of this peptide, we developed a drug delivery system by conjugating the modified gold nps.
Au nps were synthesized according to the torkevich method with little modifications by addition of trisodium citrate solution to aqueous solution of haucl4 for reduction of chloroauric acid. following that, their surface was modified by using 11-mercaptoundecanoic acid / 11-mercapto undecanol solution (mua/mu; 8:1 in 2:1 h2o/etoh) to improve the binding ability of the au nps with the designed peptide. then, for activation of carboxyl groups of mua/mu for binding to the amine group of peptide, mes buffer containing edc/nhs were used. finally, the desired peptide was dissolved in buffered dmso and then this solution was added to coated nanoparticles for synthesis of au@mua/ma@peptide nps. progressive characterization techniques including uv-vis spectroscopy, transmission electron microscope (tem), dynamic light scattering (dls), zeta potential and ftir were applied to assess the nano-dimension, dispersity, surface charge and stability of au nps and au@mua/ma@peptide nps, respectively.
Uv-vis spectroscopy as the most basic and appropriate method was used to evaluate the size of gnps and gnps-peptide in suspension. the diameter of the au nps and au-peptide nps were figured out by dls approximately under 20 nm (16 nm) and 40 nm, respectively, with a low trisodium. tem was used as a confirmation method for proofing the nano size of this compounds. also, the surface charge in the zeta potential for the free gold nps was negative (around -44) but the surface charge after conjugating au nps with was positive. these results confirmed the successful surface modification through binding desired peptide.
These conjugates could be designed in such a way as to deliver drugs in lower dose with fewer side effects by targeting specific cells especially cancer cells. synthesized au-peptide nanoparticles can be applied for the increased longevity of antiangiogenic peptides for therapeutic purposes.
Gold nanoparticles, bioconjugation, nanoparticle characterization, agiogenesis, peptide