CD73 specific siRNA loaded chitosan lactate nanoparticles potentiate the antitumor effect of a dendritic cell vaccine in 4T1 breast cancer bearing mice

Jadidi‐Niaragh, Farhad; Atyabi, Fatemeh; Rastegari, Ali; Kheshtchin, Nasim; Arab, Samaneh; Hassannia, Hadi; Ajami, Mansoureh; Mirsanei, Zahra; Habibi, Sima; Masoumi, Farimah; Noorbakhsh, Farshid; Shokri, Fazel; Hadjati, Jamshid

doi:10.1016/j.jconrel.2016.12.012

Cited by 150 publications

(112 citation statements)

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“…Conjugation of chitosan with lactate was done based on instructions provided by the previous report (Chae, Jang, & Nah, ). Generation of siRNA‐loaded NPs performed by ionic gelation of ChLa by siRNA/TPP solution, as reported previously (Jadidi‐Niaragh et al, , ). Generated ChLa NPs showed the high siRNA encapsulation efficacy and could highly protect siRNA molecules from the degradation.…”

Section: Methodsmentioning

confidence: 97%

“…A transfection efficiency was more than 50% which led to potent downregulation of CD73 expression in 4T1 cells, as details published previously (Jadidi‐Niaragh et al, ). Using FITC conjugated NPs, we have recently been shown that NPs were significantly accumulated in the tumor site in the tumor‐bearing mice (Jadidi‐Niaragh et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Several players in the tumor microenvironment such as regulatory T (Treg) cells (Jadidi‐Niaragh, Ghalamfarsa, Yousefi, Tabrizi, & Shokri, ), type two macrophages (Noy & Pollard, ), myeloid derived suppressor cells (MDSCs) (Kumar, Patel, Tcyganov, & Gabrilovich, ), natural killer T cells (Ghalamfarsa, Hadinia, Yousefi, & Jadidi‐Niaragh, ), hypoxia inducible factor (HIF) (LaGory & Giaccia, ), interleukin (IL)‐10, IL‐6, transforming growth factor (TGF)‐β, and etc., (Quail & Joyce, ) exert tumor promoting effects and decrease the efficacy of current immunotherapeutic strategies. Our previous experiences have been shown that modulation of tumor microenvironment is an effective strategy to promote the anti‐tumor immune responses (Jadidi‐Niaragh et al, ; Kheshtchin et al, ; Namdar et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Anti‐angiogenic effects of CD73‐specific siRNA‐loaded nanoparticles in breast cancer‐bearing mice

Ghalamfarsa

Rastegari

Atyabi

et al. 2018

Journal Cellular Physiology

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CD73 facilitates tumor growth by upregulation of the adenosine (immunosuppressive factor) in the tumor microenvironment, however, its precise molecular mechanisms is not precisely understood. Regarding the importance of angiogenesis in tumor development and spreading, we decided to assign the anti-angiogenic effects of CD73 suppression. We used chitosan lactate (ChLa) nanoparticles (NPs) to deliver CD73-specific small interfering RNA (siRNA) into cancer cells. Our results showed that treatment of the 4T1 cells with CD73-specific siRNA-loaded NPs led to potent inhibition of cancer cell proliferation and cell cycle arrest, in vitro. This growth arrest was correlated with downregulation of angiogenesis-related molecules including vascular endothelial growth factor (VEGF)-A, VEGF-R2, interleukin (IL)-6, and transforming growth factor (TGF)-β. Moreover, administration of NPs loaded with CD73-siRNA into 4T1 breast cancer-bearing mice led to tumor regression and increased mice survival time accompanied with downregulation of angiogenesis (VEGF-A, VEGF-R2, VE-Cadherin, and CD31) and lymphangiogenesis (VEGF-C and LYVE-1)-related genes in the tumor site. Furthermore, the expression of angiogenesis promoting factors including IL-6, TGF-β, signal transducer, and activator of transcription (STAT)3, hypoxia inducible factor (HIF)-1α, and cyclooxygenase (COX)2 was decreased after the CD73 suppression in mice. Moreover, analysis of leukocytes derived from the tumor samples, spleen, and regional lymph nodes showed that they had lower capability for secretion of angiogenesis promoting factors after CD73-silencing. These results indicate that suppression of tumor development by downregulation of CD73 is in part related to angiogenesis arrest. These findings imply a promising strategy for inhibiting tumor growth accompanied with suppressing the angiogenesis process.

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Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti‐angiogenic effects of CD73‐specific siRNA‐loaded nanoparticles in breast cancer‐bearing mice

Ghalamfarsa

Rastegari

Atyabi

et al. 2018

Journal Cellular Physiology

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“…Therefore, blockage of these checkpoint molecules and/or their ligands may be considered as a promising therapeutic strategy to restore anti‐tumor effects of T cells in the tumor microenvironment. We have demonstrated that the blockage of CD73 and adenosine A2a receptor increases the anti‐tumor potential of DC vaccines and restores T‐cell responses in tumor‐bearing mice . We have also shown that inhibition of hypoxia‐inducible factor‐1 α or adenosine receptor might enhance the efficacy of DC vaccine in animal models .…”

Section: Introductionmentioning

confidence: 87%

“…RPMI‐1640 medium, which was supplemented with 10% heat‐inactivated fetal bovine serum, 10 m m l ‐glutamine, streptomycin (100 μg/ml), and 100 units/ml penicillin (all purchased from Gibco, Grand Island, NY) was used to culture all cells in a humidified incubator at 37° and 5% CO 2 . Inoculation of tumors was performed based on our previous reports by subcutaneous injection of 7 × 10 5 4T1 cells into the right flank of syngeneic mice …”

Section: Methodsmentioning

confidence: 99%

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

et al. 2019

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Summary Dendritic cell (DC) ‐based cancer immunotherapy is one of the most important anti‐cancer immunotherapies, and has been associated with variable efficiencies in different cancer types. It is well‐known that tumor microenvironment plays a key role in the efficacy of various immunotherapies such as DC vaccine. Accordingly, the expression of programmed death ligand 1 (PD‐L1) on DCs, which interacts with PD‐1 on T cells, leads to inhibition of anti‐tumor responses following presentation of tumor antigens by DCs to T cells. Therefore, we hypothesized that down‐regulation of PD‐L1 in DCs in association with silencing of PD‐1 on T cells may lead to the enhancement of T‐cell priming by DCs to have efficient anti‐tumor T‐cell responses. In this study, we silenced the expression of PD‐L1 in DCs and programmed cell death protein 1 (PD‐1) in T cells by small interfering RNA (siRNA) ‐loaded chitosan–dextran sulfate nanoparticles (NPs) and evaluated the DC phenotypic and functional characteristics and T‐cell functions following tumor antigen recognition on DCs, ex vivo. Our results showed that synthesized NPs had good physicochemical characteristics (size 77·5 nm and zeta potential of 14·3) that were associated with efficient cellular uptake and target gene silencing. Moreover, PD‐L1 silencing was associated with stimulatory characteristics of DCs. On the other hand, presentation of tumor antigens by PD‐L1‐negative DCs to PD‐1‐silenced T cells led to induction of potent T‐cell responses. Our findings imply that PD‐L1‐silenced DCs can be considered as a potent immunotherapeutic approach in combination with PD‐1‐siRNA loaded NPs, however; further in vivo investigation is required in animal models.

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Nanoscience versus Viruses: The SARS‐CoV‐2 Case

Gościańska

Freund

Wuttke

2021

Adv Funct Materials

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The outbreak of the coronavirus (SARS‐CoV‐2) pandemic, its rapid spread, and its fatal consequences clearly showed mankind the overwhelming power of nature, and the importance of interdisciplinary research to counter it. Herein, it will be pointed out what challenges arise in fighting nanosized viruses, which feature an outstanding ability to alter their structure and properties to adapt to infection processes, and why nanoscience is extremely powerful to address them. To learn from the past and to be best prepared for the future, this review highlights how the incredible potential of nanoscience can be tapped by mimicking natures’ viruses for the development of maximally efficient pharmaceuticals, e.g., COVID‐19 vaccines, by designing preventive and protective equipment, e.g., face masks, as well as developing nanosensors for early detection of infections.

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CD73 specific siRNA loaded chitosan lactate nanoparticles potentiate the antitumor effect of a dendritic cell vaccine in 4T1 breast cancer bearing mice

Cited by 150 publications

References 46 publications

Anti‐angiogenic effects of CD73‐specific siRNA‐loaded nanoparticles in breast cancer‐bearing mice

Anti‐angiogenic effects of CD73‐specific siRNA‐loaded nanoparticles in breast cancer‐bearing mice

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

Nanoscience versus Viruses: The SARS‐CoV‐2 Case

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