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

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. 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.

SUBMITTER: Fan L

PROVIDER: S-EPMC8569206 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Gold nanorod based delivery system could bring about superior therapy effect of Ramucirumab through direct cytotoxicity to cancer cell mediated by differential regulation of phagocytosis in gastric cancer cell

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Lack of in vivo antibody dependent cellular cytotoxicity with antibody containing gold nanoparticles.

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Project description:Gastric Cancer (GC) is one of the most serious cancers with high incidence and mortality all over the world. Chemotherapy hadn’t led to desirable effect and targeted therapy brings about a new stage to cancer treatment. Ramucirumab is the first FDA-approved single drug target therapy for advanced gastric cancer. It is well known that gold nanorod, a nontoxic biocompatible nanomaterial, is an especially promising candidate for cancer theranostic. In this study, Ramucirumab (Ab) were first modified by gold nanoparticles to enhance uptake efficiency. The simple Nano-delivery system had taken perfect aggregation effect in vivo even better than 5-fold Ab treatment. Gold nanomaterials, especially gold nanorod (AuNR), could induce direct cytotoxic effect to cancer cell in the presence of Ab, while Ab or gold nanoparticle themselves couldn’t lead to such direct killing effect even at an extremely high concentration. Proteomic and transcriptomic analyses revealed this direct cytotoxicity derived predominantly from Ab-mediated phagocytose, and the high affinity receptor for Fc gamma CD64 showed differential up-regulation only in gastric cancer cell treated by these nanodrugs compared with Ab, especially for AuNR group. This was the first time to discover that nanoparticle could induce regulation of immune related pathways and Fcγ receptor in the target cancer cell. Simplified and powerful designs of smart nanoparticles are highly desired for clinical. The dramatic enhancement of Ab accumulation with simple composition, combined with direct cytotoxic effect specific to cancer cells brought perfect therapeutic effects in vivo than Ab, which would promote further clinical application of gold nanorod in the diagnosis and therapeutics of gastric cancer.

2021-07-21 | PXD027484 |

SM5-1-conjugated gold nanoparticles for antibody therapy in hepatocellular carcinoma

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SM5-1-conjugated gold nanoparticles for antibody therapy in hepatocellular carcinoma

2014-07-11 | E-GEOD-59284 | biostudies-arrayexpress

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| S-EPMC8656063 | biostudies-literature

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