Enhancing apoptosis and immunotherapy with CpG coated hollow gold nanoshells for aggressive B cell lymphoma

Project: Research project

Project Details

Description

Specific Aim 1: To determine if CpG HGNs induce direct apoptosis in lymphoma cell lines. HGNs are synthesized via a galvanic exchange reaction in which gold tetrachloroauric acid (HAuCl4) is reduced onto silver nanoparticles serving as sacrificial templates.15,16 We have extensive experience synthesizing complex HGNs that include theranostic features such as contrast agent for MRI or infrared luminance with quantum nanocrystals.17,18 The goal of this aim is to characterize the properties and efficacy of the CpG HGNs using in vitro lymphoma models. Sub-Aim 1.1: Particle characterization. Particle size is important for cellular endocytosis and gold shell thickness and size are important for tuning the absorbance to the near infrared region to maximize PTT efficacy. CpG per nanoparticle will be determined by mercaptoethanol exchange.9 Correlation between optical density with particle concentration and dose of CpG ODNs will be verified in this sub-aim. Sub-Aim 1.2: CpG HGN effects on lymphoma cell lines. Direct cytotoxic effects of CpG HGNs will be tested in various lymphoma cell lines in comparison to free CpG ODNs by viability assays. Cell lines include a double hit (MYC and BCL-2 re-arranged) DLBCL (RC), germinal center DLBCL (SUDHL4), activated B cell DLBCL (TMD8), Burkitt’s lymphoma (Ramos), and three murine lymphoma cell lines. We will evaluate changes in expression of OX40, PDL1 (as targets for checkpoint inhibitors), SR-B1 (targets for HDL mimic nanoparticles by our group), as well as maturation markers and cytokine releases. Sub-Aim1.3: Immune stimulatory effects of CpG HGNs on APCs. Murine macrophage cells and immature murine dendritic cells will be cultured with CpG HGNs and compared with free CpGs at various time points. Activation of the macrophages and dendritic cells will be monitored and quantified by evaluating the upregulation of maturation markers with flow cytometry. ELISAs will be used to quantify inflammatory cytokine release. Expected r
StatusFinished
Effective start/end date7/1/196/30/20

Funding

  • American Society of Hematology (Agmt 5/1/19)

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