Gold nanoparticles enhance antibody effect through direct cancer cell cytotoxicity by differential regulation of phagocytosis

• Published in: Nature communications 2021-11, Vol.12 (1), p.6371-13, Article 6371
• Main Authors: Fan, Linyang, Wang, Weizhi, Wang, Zihua, Zhao, Minzhi
• Format: Article
• Language: English
• Subjects: 147/143; 49/1; 59/5; 631/67/1059/2325; 639/925/352; 692/4028/67/1059/602; 82/58; 96/31; 96/47; Animals; Antibodies; Antibodies, Monoclonal, Humanized - chemistry; Antibodies, Monoclonal, Humanized - pharmacology; Anticancer properties; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biocompatibility; Cell Line, Tumor; Conjugation; Cytotoxicity; Fc receptors; Female; Gastric cancer; Gold; Gold - administration & dosage; Gold - chemistry; Humanities and Social Sciences; Humans; Immunotherapy; Metal Nanoparticles - administration & dosage; Metal Nanoparticles - chemistry; Mice; Mice, Inbred BALB C; Mice, Nude; multidisciplinary; Nanomaterials; Nanoparticles; Nanorods; Nanotechnology; Phagocytosis; Proteomics; Ramucirumab; Science; Science (multidisciplinary); Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Toxicity; Transcriptomics; Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors; Xenograft Model Antitumor Assays
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26694-x

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. Antibody therapies have huge potential in treating cancer but currently suffer from problems with delivery. Here the authors report on a study into then conjugation of Ramucirumab to gold nanoparticles to improve delivery and add theranostic capabilities, demonstrating preferential toxicity in gastric cancer cells.