Abstract
Ramucirumab is the first FDA-approved monotherapy for advanced gastric cancer. In this study, Ramucirumab (Ab) is attached to gold nanoparticles to enhance uptake efficiency. Gold nanoparticles can induce direct cytotoxic effects to cancer cells in the presence of Ab, while individual Ab or gold nanoparticles don’t have such an effective anticancer effect even at extremely high concentrations. Proteomic and transcriptomic analyses reveal this direct cytotoxicity is derived predominantly from Ab-mediated phagocytosis. High affinity immunoglobulin gamma Fc receptor I shows differential up-regulation in gastric cancer cells treated by these nanodrugs compared with Ab, especially for Ab with gold nanorods. Simplified and powerful designs of smart nanoparticles are highly desired for clinical application. The enhancement of Ab accumulation with a simple composition, combined with direct cytotoxic effects specific to cancer cells brought improved therapeutic effects in vivo compared with Ab, which can promote further clinical application of gold nanomaterials in the diagnosis and therapeutics of gastric cancer.
Highlights
Ramucirumab is the first FDA-approved monotherapy for advanced gastric cancer
It is an undeniable fact that 5-year relative survival rate was double by modern diagnosis and tumor therapies development in 40 year since several gastric relative targets had been discovered, like Epidermal growth factor receptor (EGFR)[5], Human epidermal growth factor receptor 2(HER2)[6], Vascular endothelial growth factor(VEGF) family[7], Mesenchymal-epithelial transition factor(MET)(8) and Programmed death1(PD1): PDL (PD-ligand) 1/PDL2 pathway[8]
There were obvious capsules on the surface of gold nanorods (AuNR) and nanosphere (AuSP) characterization by TEM (200,000×), which confirmed the successful coating on the surface of the gold nano-particles (Fig. 2a, b)
Summary
Ramucirumab is the first FDA-approved monotherapy for advanced gastric cancer. In this study, Ramucirumab (Ab) is attached to gold nanoparticles to enhance uptake efficiency. The results indicated that neither gold nanomaterials nor other linkers had cell inhibition effect, except for DOX (Fig. 4e, i, k).
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