Dataset Information

A nano-innate immune system activator for cancer therapy in a 4T1 tumor-bearing mouse model.

ABSTRACT:

Background

Harnessing the immune system to fight cancer has led to prominent clinical successes. Strategies to stimulate innate immune effectors are attracting considerable interest in cancer therapy. Here, through conjugating multivalent Fc fragments onto the surface of mesoporous silica nanoparticles (MSN), we developed a nanoparticle-based innate immune system activator (NISA) for breast cancer immunotherapy.

Methods

NISA was prepared through conjugating mouse IgG3 Fc to MSN surface. Then, long-chain PEG₅₀₀₀, which was used to shield Fc to confer nanoparticle colloidal stability, was linked to the MSN surface via matrix metalloprotease-2 (MMP-2)-cleavable peptide (GPLGIAGQC). The activation of multiple components of innate immune system, including complement and the innate cells (macrophages and dendritic cells) and the associated anticancer effect were investigated.

Results

Fc fragments of NISA can be exposed through hydrolysis of long-chain PEG₅₀₀₀ by highly expressed MMP-2 in tumor microenvironment. Then, effective stimulation and activation of multiple components of innate immune system, including complement, macrophages, and dendritic cells were obtained, leading to efficient antitumor effect in 4T1 breast cancer cells and orthotopic breast tumor model in mice.

Conclusions

The antitumor potency conferred by NISA highlights the significance of stimulating multiple innate immune elements in cancer immunotherapy.

SUBMITTER: Liu XY

PROVIDER: S-EPMC8800325 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

A nano-innate immune system activator for cancer therapy in a 4T1 tumor-bearing mouse model.

Liu Xiang-Yu XY Zhu Mao-Hua MH Wang Xiao-Yu XY Dong Xiao X Liu Hai-Jun HJ Li Rui-Yang RY Jia Shi-Chong SC Lu Qin Q Zhao Mei M Sun Peng P Chen Hong-Zhuan HZ Fang Chao C

Journal of nanobiotechnology 20220129 1

<h4>Background</h4>Harnessing the immune system to fight cancer has led to prominent clinical successes. Strategies to stimulate innate immune effectors are attracting considerable interest in cancer therapy. Here, through conjugating multivalent Fc fragments onto the surface of mesoporous silica nanoparticles (MSN), we developed a nanoparticle-based innate immune system activator (NISA) for breast cancer immunotherapy.<h4>Methods</h4>NISA was prepared through conjugating mouse IgG3 Fc to MSN su ...[more]

PMID: 35093074

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Project description:In mammalian species, mitochondrial DNA (mtDNA) with pathogenic mutations that induce mitochondrial respiration defects has been proposed to be involved in tumor phenotypes via induction of enhanced glycolysis under normoxic conditions (the Warburg effects). However, because both nuclear DNA and mtDNA control mitochondrial respiratory function, it is difficult to exclude the possible contribution of nuclear DNA mutations to mitochondrial respiration defects and the resultant expression of tumor phenotypes. Therefore, it is important to generate transmitochondrial cybrids sharing the same nuclear DNA background but carrying mtDNA with and without the mutations by using intercellular mtDNA transfer technology. Our previous studies isolated transmitochondrial cybrids and showed that specific mtDNA mutations enhanced tumor progression as a consequence of overproduction of reactive oxygen species (ROS). This study assessed whether mtDNA mutations inducing ROS overproduction always enhance tumor progression. We introduced mtDNA from senescence-accelerated mice P1 (SAMP1) into C57BL/6J (B6) mice-derived Lewis lung carcinoma P29 cells, and isolated new transmitochondrial cybrids (P29mtSAMP1 cybrids) that overproduced ROS. The inoculation of the cybrids into B6 mice unexpectedly showed that mtDNA from SAMP1 mice conversely induced tumor suppression. Moreover, the tumor suppression of P29mtSAMP1 cybrids in B6 mice occurred as a consequence of innate immune responses of the host B6 mice. Enzyme pretreatment experiments of P29mtSAMP1 cybrids revealed that some peptides encoded by mtDNA and expressed on the cell surface of P29mtSAMP1 cybrids induce increased IL-6 production from innate immune cells (dendritic cells) of B6 mice, and mediate augmented inflammatory responses around the tumor-inoculated environment. These observations indicate presence of a novel role of mtDNA in tumor phenotype, and provide new insights into the fields of mitochondrial tumor biology and tumor immunology.

Dataset Information

A nano-innate immune system activator for cancer therapy in a 4T1 tumor-bearing mouse model.

Background

Methods

Results

Conclusions

Publications

A nano-innate immune system activator for cancer therapy in a 4T1 tumor-bearing mouse model.

Similar Datasets

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