Targeted ferritin nanoparticle encapsulating CpG oligodeoxynucleotides induces tumor-associated macrophage M2 phenotype polarization into M1 phenotype and inhibits tumor growth

Shan, Hui; Dou, Wenlong; Zhang, Yu; Qi, Mi

doi:10.1039/d0nr04520a

Cited by 75 publications

(48 citation statements)

References 46 publications

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“…In addition, other nanoparticulate CpG oligodeoxynucleotides delivered into immunosuppressive TAMs and repolarized TAMs to immunogenic M1 phenotype and exhibited anti‐tumor effects in mice models. The reversal of phenotype of cultured human macrophages was also demonstrated in vitro 96 . These studies suggest that immunotherapy combined with nanoparticulate CpG oligodeoxynucleotides are a promising strategy to achieve a major breakthrough in immunosuppressive PDAC treatment.…”

Section: Targeting Immunosuppressive Barriers In the Tumor Microenvironmentmentioning

confidence: 65%

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Advances in immunotherapy for pancreatic ductal adenocarcinoma

Miyazawa

Katsuda

Kawai

et al. 2021

J Hepato Biliary Pancreat

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Pancreatic ductal adenocarcinoma (PDAC) is a recalcitrant disease with 5-year survival at less than 10%. 1 Meanwhile, recent innovative advances in immunotherapy, particularly immune checkpoint inhibitors (ICIs), have had significant clinical benefit in other cancers (Table 1). 2 The main reason why PDAC is refractory to immunotherapies including ICIs is that it is a so-called "cold tumor." 3,4 The tumor microenvironment (TME) in cold tumors, such as PDAC and glioblastomas, is rich in suppressive immune cells, but there are few infiltrations of cytotoxic immune cells with abundant cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM). 5 Conversely, "hot tumors," including melanomas and non-small cell lung cancer, have a TME with T-cell infiltration and they tend to respond well to ICIs. 6 Tumor-infiltrating lymphocytes (TILs) in PDAC can also be used to predict its prognosis, [7][8][9] indicating that PDAC immunotherapy has

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Section: Targeting Immunosuppressive Barriers In the Tumor Microenvironmentmentioning

confidence: 65%

“…The reversal of phenotype of cultured human macrophages was also demonstrated in vitro. 96 These studies suggest that immunotherapy combined with nanoparticulate CpG oligodeoxynucleotides are a promising strategy to achieve a major breakthrough in immunosuppressive PDAC treatment.…”

Section: Vaccine Adjuvantsmentioning

confidence: 99%

Advances in immunotherapy for pancreatic ductal adenocarcinoma

Miyazawa

Katsuda

Kawai

et al. 2021

J Hepato Biliary Pancreat

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“…From this perspective, E2-ferritin nanocage vaccines are proven to be safe and are worth promoting. Infectious viral pathogen-interrelated nanovaccines and self-assembling ferritin nanocages are also being developed in therapeutic anticancer nanomedicines, such as a targeted ferritin nanoparticle that inhibits tumor growth via a novel cancer immunotherapy strategy of encapsulating CpG oligodeoxynucleotides [33].…”

Section: Discussionmentioning

confidence: 99%

A Self-Assembling Ferritin Nanoplatform for Designing Classical Swine Fever Vaccine: Elicitation of Potent Neutralizing Antibody

Zhao

Chen

et al. 2021

Vaccines

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Protein-based self-assembling nanoplatforms exhibit superior immunogenicity compared with soluble antigens. Here, we present a comprehensive vaccine strategy for displaying classical swine fever virus (CSFV) E2 glycoprotein on the surface of ferritin (fe) nanocages. An E2-specific blocking antibody assay showed that the blocking rates in pE2-fe/Gel02 (84.3%) and a half-dose cohort of E2-fe/Gel02 (81.9%) were significantly higher (p < 0.05) than that in a ferritin-free cohort of pE2/Gel02 (62.7%) at 21 days post immunization (dpi) in vivo. Furthermore, quantitation of neutralizing potency revealed that a highly significant difference (p < 0.001) was observed between the pE2-fe/Gel02 cohort (1:32, equivalent to live-attenuated strain C at 1:32) and the pE2/Gel02 cohort (1:4) at 21 dpi. Moreover, the innate immune cytokines of IL-4 and IFN-γ activated by the half-dose (20 μg) cohort of E2-fe/Gel02 were equivalent to those elicited by the full dose (40 μg) of purified E2 in the pE2/Gel02 cohort at most time points. In conclusion, we successfully obtained an antigen-displaying E2-ferritin nanoplatform and confirmed high ferritin-assisted humoral and cellular immunities. Our results provided a novel paradigm of self-assembling nanovaccine development for the defense and elimination of potentially pandemic infectious viral pathogens.

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“…Other authors have also suggested the use of TLR7 and TLR8 agonists to induce the activation of NF-κB to enhance immunotherapy efficacy and to increase TNF-α and IL-6 secretion [ 129 ]. For example, Shan et al used human ferritin heavy chain nanocages modified with M2pep to deliver a TLR agonist in a murine breast cancer model [ 116 ]. TLR agonist triggered TLR signaling and polarized TAM into M1 inflammatory macrophages [ 116 ].…”

Section: Nanoparticles To Target and Treat Tumour-associated Macrophagesmentioning

confidence: 99%

“…For example, Shan et al used human ferritin heavy chain nanocages modified with M2pep to deliver a TLR agonist in a murine breast cancer model [ 116 ]. TLR agonist triggered TLR signaling and polarized TAM into M1 inflammatory macrophages [ 116 ].…”

Section: Nanoparticles To Target and Treat Tumour-associated Macrophagesmentioning

confidence: 99%

Nanoparticles to Target and Treat Macrophages: The Ockham’s Concept?

2021

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Nanoparticles are nanomaterials with three external nanoscale dimensions and an average size ranging from 1 to 1000 nm. Nanoparticles have gained notoriety in technological advances due to their tunable physical, chemical, and biological characteristics. However, the administration of functionalized nanoparticles to living beings is still challenging due to the rapid detection and blood and tissue clearance by the mononuclear phagocytic system. The major exponent of this system is the macrophage. Regardless the nanomaterial composition, macrophages can detect and incorporate foreign bodies by phagocytosis. Therefore, the simplest explanation is that any injected nanoparticle will be probably taken up by macrophages. This explains, in part, the natural accumulation of most nanoparticles in the spleen, lymph nodes, and liver (the main organs of the mononuclear phagocytic system). For this reason, recent investigations are devoted to design nanoparticles for specific macrophage targeting in diseased tissues. The aim of this review is to describe current strategies for the design of nanoparticles to target macrophages and to modulate their immunological function involved in different diseases with special emphasis on chronic inflammation, tissue regeneration, and cancer.

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Targeted ferritin nanoparticle encapsulating CpG oligodeoxynucleotides induces tumor-associated macrophage M2 phenotype polarization into M1 phenotype and inhibits tumor growth

Abstract: Tumor-associated macrophages (TAM) are primarily of the M2 type that facilitates tumor growth, metastasis, and immunosuppression. Therefore, repolarizing the TAMs to the pro-inflammatory M1 type is a promising therapeutic strategy...

Cited by 75 publications

References 46 publications

Advances in immunotherapy for pancreatic ductal adenocarcinoma

Advances in immunotherapy for pancreatic ductal adenocarcinoma

A Self-Assembling Ferritin Nanoplatform for Designing Classical Swine Fever Vaccine: Elicitation of Potent Neutralizing Antibody

Nanoparticles to Target and Treat Macrophages: The Ockham’s Concept?

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