Efficient Lymph Node-Targeted Delivery of Personalized Cancer Vaccines with Reactive Oxygen Species-Inducing Reduced Graphene Oxide Nanosheets

Cheng, Xu; Hong, Hao; Lee, Yonghyun; Park, Kyong Soo; Sun, Mingjiao; Wang, Tianrui; Aikins, Marisa; Xu, Yao; Moon, James J.

doi:10.1021/acsnano.0c05062

Cited by 77 publications

(62 citation statements)

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“…Interestingly, the production of TNFα by peritoneal macrophages decreased after 24 h of incubation but increased after 48 h [ 37 ]. In the same papers, the increase of TNFα production did not correlate with changes in the production of IL-10, IL-6, and other cytokines [ 36 , 56 , 65 ]. Importantly, most cited studies lack information about endotoxin content in tested nanoparticle preparations which significantly complicates the comparative analysis of their results.…”

Section: Resultsmentioning

confidence: 96%

“…Six-armed and linear PEG-modified GO increased ROS production in osteoblasts and macrophages (RAW-264.7) [ 22 ]. Reduced GO-PEG stimulated production of intracellular ROS in mice bone marrow-derived dendritic cells and bone marrow mesenchymal stem cells [ 55 , 56 ]. At the same time, two research groups have demonstrated that GO-PEG did not stimulate the production of intracellular ROS in human breast cancer cells (MCF-7) [ 35 , 57 ].…”

Section: Resultsmentioning

confidence: 99%

“…We did not assess the number of PEG chains per one GO nanoparticle, but the mass fraction of PEG was almost the same in all GO-PEG. Some authors demonstrated enhanced secretion of TNFα by RAW-264.7 macrophages [ 36 ], peritoneal macrophages [ 65 ], and mice bone marrow-derived dendritic cells [ 56 ]. Interestingly, the production of TNFα by peritoneal macrophages decreased after 24 h of incubation but increased after 48 h [ 37 ].…”

Section: Resultsmentioning

confidence: 99%

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Interaction of Graphene Oxide Modified with Linear and Branched PEG with Monocytes Isolated from Human Blood

et al. 2021

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Multiple graphene-based therapeutics have recently been developed, however potential risks related to the interaction between nanomaterials and immune cells are still poorly understood. Therefore, studying the impact of graphene oxide on various populations of immune cells is of importance. In this work, we aimed to investigate the effects of PEGylated graphene oxide on monocytes isolated from human peripheral blood. Graphene oxide nanoparticles with lateral sizes of 100–200 nm and 1–5 μm were modified with linear and branched PEG (GO-PEG). Size, elemental composition, and structure of the resulting nanoparticles were characterized. We confirmed that PEG was successfully attached to the graphene oxide surface. The influence of GO-PEG on the production of reactive oxygen species (ROS), cytokines, phagocytosis, and viability of monocytes was studied. Uptake of GO-PEG by monocytes depends on PEG structure (linear or branched). Branched PEG decreased the number of GO-PEG nanoparticles per monocyte. The viability of monocytes was not altered by co-cultivation with GO-PEG. GO-PEG decreased the phagocytosis of Escherichia coli in a concentration-dependent manner. ROS formation by monocytes was determined by measuring luminol-, lucigenin-, and dichlorodihydrofluorescein-dependent luminescence. GO-PEG decreased luminescent signal probably due to inactivation of ROS, such as hydroxyl and superoxide radicals. Some types of GO-PEG stimulated secretion of IL-10 by monocytes, but this effect did not correlate with their size or PEG structure.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Interaction of Graphene Oxide Modified with Linear and Branched PEG with Monocytes Isolated from Human Blood

et al. 2021

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“…In addition, Xu et al . [ 46 ] showed that s.c. injection of PEGylated reduced graphene oxide nanosheet (RGO-PEG, 20–30 nm in diameter) with high colloidal stability could rapidly deliver 15–20% of the loaded neoantigens to LN and retained it for up to 72 h, achieving > 100-fold improvement in LN-targeted delivery when compared with soluble vaccines. Not only that, the direct interaction between RGO-PEG nanovaccines and DCs in LN induced intracellular reactive oxygen species (ROS), which further increased the antigen processing and presentation capacity of DCs, thereby eliciting potent and durable (up to 30 days) neoantigen-specific T cell responses to eradicate the established MC-38 colon carcinoma.…”

Section: Delivery Of Nanovaccines To Lnmentioning

confidence: 99%

Delivery of nanovaccine towards lymphoid organs: recent strategies in enhancing cancer immunotherapy

et al. 2021

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With the in-depth exploration on cancer therapeutic nanovaccines, increasing evidence shows that the poor delivery of nanovaccines to lymphoid organs has become the culprit limiting the rapid induction of anti-tumor immune response. Unlike the conventional prophylactic vaccines that mainly form a depot at the injection site to gradually trigger durable immune response, the rapid proliferation of tumors requires an efficient delivery of nanovaccines to lymphoid organs for rapid induction of anti-tumor immunity. Optimization of the physicochemical properties of nanovaccine (e.g., size, shape, charge, colloidal stability and surface ligands) is an effective strategy to enhance their accumulation in lymphoid organs, and nanovaccines with dynamic structures are also designed for precise targeted delivery of lymphoid organs or their subregions. The recent progress of these nanovaccine delivery strategies is highlighted in this review, and the challenges and future direction are also discussed. Graphical Abstract

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“…For instance, GO and rGO have been used as potential vaccine adjuvants to improve the antigen immunogenicity for better cancer treatment. [30][31][32] In addition, GO-templated antibody nanoclusters could activate human natural killer cells for immunotherapy. [33] To further enhance the therapeutic efficiency, GFMs have been transformed into multifunctional platforms for combined cancer therapy.…”

Section: Graphene Family Materialsmentioning

confidence: 99%

Recent Advances in 2D Material‐Mediated Immuno‐Combined Cancer Therapy

Bianco

2021

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metal carbides or nitrides. [3][4][5][6][7][8] Based on their different properties, such 2D materials could be used as efficient means for drug delivery, photothermal therapy (PTT, which utilizes photothermal agents to convert light energy into hyperthermia, leading to the thermal ablation of cancer cells), photodynamic therapy (PDT, which uses photosensitizers to transfer photon energy into reactive oxygen species, provoking cancer cell death), chemodynamic therapy (CDT, which is based on Fenton or Fenton-like reactions to convert H 2 O 2 into hydroxyl radicals triggering apoptosis and inhibiting tumor growth), radiotherapy (RT, which uses high-dose radiation to kill cancer cells and eliminate tumors), radiodynamic therapy (RDT, which utilizes ionizing radiation to excite photosensitizers to generate 1 O 2 against cancer), and specific combination thereof. [8][9][10] In the years, cancer immunotherapy gets exceptional growing progress, especially after ipilimumab obtained the approval from FDA. [11] Ipilimumab is a monoclonal antibody directed towards cytotoxic T-lymphocyte-associated protein 4 (CTLA4) showing a significant increase in the survival of patients with metastatic melanoma. It is well known that cancer immunotherapy is based on immune system activation to target and eradicate cancer cells with durable antitumor responses and less metastasis and recurrence than other therapeutic strategies. [12,13] Immune biochemical factors, vaccines, checkpoint inhibitors, monoclonal antibodies, and other molecules have been widely utilized as efficient modulators to activate the immune system. Checkpoint blockade immunotherapy is a recently developed strategy based on the use of checkpoint inhibitors to arrest the immunosuppressive pathways promoting antitumor T cell activation and maintaining the antitumor T cell effector function. [14,15] However, the cancer immunotherapy efficiency is still not satisfactory. Indeed, the overall patient response rates are usually below 40% by checkpoint inhibitor therapy. [16] Meanwhile, immunotherapy can trigger mild to serious side effects, such as nausea, vomiting, lung/skin/gastrointestinal/renal toxicities, hypothyroidism, arthralgia, vasculitis, autoimmune hepatitis, and other dysfunctions. [17,18] To reduce or to overcome the side effects caused by immunotherapy, and further enhance its efficiency, 2D materials provide incomparable advantages, including high specific surface area, biocompatibility, chemical surface modification, targeting possibility, tumor accumulation, and unique physicochemical In the last years, cancer immunotherapy has started to attract a lot of attention, becoming one of the alternatives in the clinical treatment of cancer. Indeed, one of the advantages of immunotherapy is that both primary and distant tumors can be efficiently eradicated through a triggered immune response. Due to their large specific surface area and unique physicochemical properties, 2D materials have become popular in cancer immunotherapy, especially as efficient drug carriers. ...

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Efficient Lymph Node-Targeted Delivery of Personalized Cancer Vaccines with Reactive Oxygen Species-Inducing Reduced Graphene Oxide Nanosheets

Cited by 77 publications

References 44 publications

Interaction of Graphene Oxide Modified with Linear and Branched PEG with Monocytes Isolated from Human Blood

Interaction of Graphene Oxide Modified with Linear and Branched PEG with Monocytes Isolated from Human Blood

Delivery of nanovaccine towards lymphoid organs: recent strategies in enhancing cancer immunotherapy

Recent Advances in 2D Material‐Mediated Immuno‐Combined Cancer Therapy

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