Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines

Xu, Pingping; Tang, Shuai; Jiang, Luping; Yang, Lihua; Zhang, Dinglin; Feng, Shibin; Zhao, Tingting; Dong, Ya-Jun; Wang, He; Wang, Ruibing; Zhang, Jianxiang; Liang, Zhiqing

doi:10.1016/j.jconrel.2016.01.043

Cited by 15 publications

(11 citation statements)

References 69 publications

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“…Previous studies have reported an apparent decrease in testis and epididymal weights, as well as obvious pathologic changes in the seminiferous tubules, of immunization animals . However, other studies have shown no pathological changes in the testis and epididymis . Our study was consistent with the latter.…”

Section: Discussionsupporting

confidence: 92%

“…3,[27][28][29] However, other studies have shown no pathological changes in the testis and epididymis. 1,15,16,30 Our study was consistent with the latter. Collectively, these results suggest that peptides derived from ZNF185 may be a safe male contraceptive vaccine that avoids the side effects of current available contraceptive methods.…”

Section: Analysis Of Male Reproductive Organssupporting

confidence: 92%

“…Measurements of antibody titres were performed as described in a previous study . The antibody titre was measured by ELISA.…”

Section: Methodsmentioning

confidence: 99%

“…Measurements of antibody titres were performed as described in a previous study. 15 The antibody titre was measured by ELISA. The 96-well microtitre plate was coated with antigen proteins and incubated at 4°C overnight and then blocked using 5% bovine serum albumin (BSA) for 1 hour at 37°C.…”

Section: Measurement Of Antibody Titresmentioning

confidence: 99%

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ZNF185‐derived peptide induces fertility suppression in mice

Fan

Zhao

Pan

et al. 2018

Journal of Peptide Science

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Zinc finger protein 185 (ZNF185) belongs to the ZNF family and is involved in male reproduction. However, it is unclear whether ZNF185 may be a target candidate for contraceptive vaccines. In this study, antigenic peptides derived from ZNF185 were prepared, and their immune contraceptive effects were investigated using mice. Results from enzyme‐linked immunosorbent assay (ELISAs) showed that peptide immunization induced an antibody titre increase that reached a peak in week 12. Peptide‐3 and peptide‐4 were then chosen for subsequent experiments. The results of the fertility assays showed that peptide immunization inhibited the mating and fertility rates of the mice, whereas there were no obvious changes in the number of pups per litter. Subsequently, epididymal sperm was analysed. The results demonstrated that the sperm count and sperm motility were significantly decreased in the peptide group, while the amount of abnormal sperm was significantly increased in the peptide‐3 group. The male reproductive organs were also evaluated. There were no obvious differences in testis or epididymal weights, in the diameters of the seminiferous tubules, or in the thicknesses of the seminiferous epithelium between the peptide group and the phosphate buffer saline (PBS) group. In addition, histological analysis indicated that there were no obvious pathologic changes in testis and epididymal histology in the peptide group; however, the number of spermatozoa present in the epididymal lumen of the peptide group was significantly decreased when compared with the PBS group. Our study demonstrates for the first time that peptides derived from ZNF185 may induce fertility suppression in mice without damaging reproductive organs. These peptides have the potential to be used as a male contraceptive vaccine.

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Section: Discussionsupporting

confidence: 92%

Section: Analysis Of Male Reproductive Organssupporting

confidence: 92%

“…Measurements of antibody titres were performed as described in a previous study . The antibody titre was measured by ELISA.…”

Section: Methodsmentioning

confidence: 99%

Section: Measurement Of Antibody Titresmentioning

confidence: 99%

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ZNF185‐derived peptide induces fertility suppression in mice

Fan

Zhao

Pan

et al. 2018

Journal of Peptide Science

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“…Immune imprinting or “innate training” is a phenomenon wherefore non antigenic stimuli (e.g., toll-like receptor ligands or NP) alter the capacity of the immune system to react to subsequent unrelated stimuli ( 13 , 14 ). Some innate training mechanisms include impairment of pulmonary antigen-presenting cell (APC) function ( 9 , 15 ), altered antigen delivery ( 16 ), and induction of regulatory myeloid-derived suppressor cells ( 12 ). Previously, we demonstrated that PS50G not only negatively imprint inflammatory CD11b hi dendritic cell (DC) but also increase the frequency of CD103 + DC in the lung ( 9 ), a population that contributes to airway homeostasis by inducing Foxp3 + regulatory T cells (Treg) ( 17 ), through a Treg-independent production of IL-10 ( 18 ) or IL-12 ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

Synthetic Nanoparticles That Promote Tumor Necrosis Factor Receptor 2 Expressing Regulatory T Cells in the Lung and Resistance to Allergic Airways Inflammation

et al. 2017

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Synthetic glycine coated 50 nm polystyrene nanoparticles (NP) (PS50G), unlike ambient NP, do not promote pulmonary inflammation, but instead, render lungs resistant to the development of allergic airway inflammation. In this study, we show that PS50G modulate the frequency and phenotype of regulatory T cells (Treg) in the lung, specifically increasing the proportion of tumor necrosis factor 2 (TNFR2) expressing Treg. Mice pre-exposed to PS50G, which were sensitized and then challenged with an allergen a month later, preferentially expanded TNFR2+Foxp3+ Treg, which further expressed enhanced levels of latency associated peptide and cytotoxic T-lymphocyte associated molecule-4. Moreover, PS50G-induced CD103+ dendritic cell activation in the lung was associated with the proliferative expansion of TNFR2+Foxp3+ Treg. These findings provide the first evidence that engineered NP can promote the selective expansion of maximally suppressing TNFR2+Foxp3+ Treg and further suggest a novel mechanism by which NP may promote healthy lung homeostasis.

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Site‐Specific MicroRNA‐33 Antagonism by pH‐Responsive Nanotherapies for Treatment of Atherosclerosis via Regulating Cholesterol Efflux and Adaptive Immunity

Ding

Chen

et al. 2020

Adv Funct Materials

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Atherosclerosis remains the leading cause of a broad spectrum of deadliest cardiovascular diseases. MicroRNA-33 is a new therapeutic target for atherosclerosis due to its diverse functions. However, it remains a great challenge in clinical translation of nucleic acid-based microRNA-targeting therapeutics. Considering lesional acidosis, herein cyclodextrin-derived pH-responsive and integrin-targeting nanoparticles containing an antisense oligonucleotide against microRNA-33 (anti-miR33) are engineered for precision therapy of atherosclerosis. A desirable anti-miR33 nanotherapy (AAM NP) is initially developed by screening carrier materials. AAM NP is further decorated with a peptide ligand cRGDfK for integrin to afford an active targeting nanotherapy RAAM NP, to achieve more effective delivery of anti-miR33 to plaques and target cells. Both nanotherapies can be efficiently internalized by different cells relevant to atherosclerosis. After intravenous delivery, AAM NP passively accumulates in atherosclerotic plaques and related cells in apolipoprotein E-deficient mice. Correspondingly, AAM NP treatment significantly attenuates atherosclerosis in mice and notably reduces vulnerable plaques. Decoration with cRGDfK considerably enhances the targeting capability and therapeutic effects of RAAM NP. Mechanistically, anti-miR33 nanotherapies significantly promote reverse cholesterol transport and notably regulate adaptive immunity via modulating macrophage polarization and regulatory T cell differentiation. Consequently, the pH-responsive anti-miR33 nanotherapies are promising for targeted treatment of atherosclerosis.

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Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines

Cited by 15 publications

References 69 publications

ZNF185‐derived peptide induces fertility suppression in mice

ZNF185‐derived peptide induces fertility suppression in mice

Synthetic Nanoparticles That Promote Tumor Necrosis Factor Receptor 2 Expressing Regulatory T Cells in the Lung and Resistance to Allergic Airways Inflammation

Site‐Specific MicroRNA‐33 Antagonism by pH‐Responsive Nanotherapies for Treatment of Atherosclerosis via Regulating Cholesterol Efflux and Adaptive Immunity

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