H1/pHGFK1 nanoparticles exert anti-tumoural and radiosensitising effects by inhibition of MET in glioblastoma

Zhang, Wenyan; Duan, Rui; Zhang, Jian; Cheung, William K.C.; Gao, Xiaoge; Zhang, Raymond; Zhang, Qing; Wei, Meng-Xue; Wang, Gang; Zhang, Qian; Mei, Peng-jin; Chen, Honglin; Kung, Hsiang‐Fu; Lin, Marie C.; Shen, Zan; Zheng, Junnian; Zhang, Longzhen; Yao, Hong

doi:10.1038/bjc.2017.461

Cited by 18 publications

(31 citation statements)

References 43 publications

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“…Compared with conventional live or subunit vaccines, DNA vaccines are easy to manufacture, are highly stable, and generally present fewer safety concerns than other types of vaccines (10). H1 nanoparticles have been applied to a safe system for DNA delivery (28). AIM2 is a host protein and vaccination with H1-pAIM2/pCAIX vaccine might have inflammation risk.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown significant success using H1 nanoparticle-based delivery system to deliver genes in mice. This delivery system also did not show elevated inflammation in serum or a nonspecific immune response in vivo, suggesting its low toxicity (27,28). Therefore, H1 nanoparticlebased delivery system may enhance the therapeutic effect of DNA vaccine for tumor treatment.…”

Section: Introductionmentioning

confidence: 91%

“…Therefore, safe and efficient vaccine carriers are key to clinical success of vaccine therapy. Folate-grafted PEI600-CyD (H1) as a vehicle of nonviral gene could effectively condense DNA vaccine to form stable functionalized nanoparticles for vaccine delivery (27,28). Recent studies have shown significant success using H1 nanoparticle-based delivery system to deliver genes in mice.…”

Section: Introductionmentioning

confidence: 99%

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Combining DNA Vaccine and AIM2 in H1 Nanoparticles Exert Anti-Renal Carcinoma Effects via Enhancing Tumor-Specific Multi-functional CD8+ T-cell Responses

Chai

Shan

Wang

et al. 2019

Molecular Cancer Therapeutics

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Renal carcinoma presents a rapid progression in patients with high metastasis with no effective therapeutic strategy. In this study, we designed a folate-grafted PEI600-CyD (H1) nanoparticle-mediated DNA vaccine containing an adjuvant of absent in melanoma 2 (AIM2) and a tumor-specific antigen of carbonic anhydrase IX (CAIX) for renal carcinoma therapy. Mice bearing subcutaneous human CAIX (hCAIX)-Renca tumor were intramuscularly immunized with H1-pAIM2/pCAIX, H1-pCAIX, H1-pAIM2, or Mock vaccine, respectively. The tumor growth of hCAIX-Renca was significantly inhibited in H1-pAIM2/pCAIX vaccine group compared with the control group. The vaccine activated CAIX-specific CD8 þ T-cell proliferation and CTL responses, and enhanced the induction of multi-functional CD8 þ T cells (expressing TNF-a, IL-2, and IFN-g).CD8 þ T-cell depletion resulted in the loss of anti-tumor activity of H1-pAIM2/pCAIX vaccine, suggesting that the efficacy of the vaccine was dependent on CD8 þ T-cell responses. Lung metastasis of renal carcinoma was also suppressed by H1-pAIM2/pCAIX vaccine treatment accompanied with the increased percentages of CAIX-specific multi-functional CD8 þ T cells in the spleen, tumor, and bronchoalveolar lavage as compared with H1-pCAIX vaccine. Similarly, the vaccine enhanced CAIX-specific CD8 þ T-cell proliferation and CTL responses. Therefore, these results indicated that H1-pAIM2/pCAIX vaccine exhibits the therapeutic efficacy of anti-renal carcinoma by enhancing tumor-specific multi-functional CD8 þ T-cell responses. This vaccine strategy could be a potential and promising approach for the therapy of primary solid or metastasis tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Combining DNA Vaccine and AIM2 in H1 Nanoparticles Exert Anti-Renal Carcinoma Effects via Enhancing Tumor-Specific Multi-functional CD8+ T-cell Responses

Chai

Shan

Wang

et al. 2019

Molecular Cancer Therapeutics

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“…Our previous study has demonstrated that H1 nanoparticles were an effective delivery system for gene expression in vitro and in vivo. 26 Thus, H1/pAIM2 or control nanoparticles were prepared (Figure 2A) and transiently transfected into 786-O or OSRC-2 cells. The result showed AIM2 expression was significantly increased in both renal cancer cell lines as compared with control ( Figure 2B).…”

Section: H1/aim2 Inhibited Renal Cancer Cell Proliferation and Prommentioning

confidence: 99%

“…Folate‐grafted PEI600‐CyD (H1) as a non‐viral gene delivery vehicle can effectively condense plasmid DNA to form stable functionalized nanoparticles . Recent studies have shown a significant success using H1 to deliver genes in vivo . More importantly, H1‐based delivery system leads to neither elevate enzymes in serum nor a non‐specific immune response in mice, suggesting its low toxicity .…”

Section: Introductionmentioning

confidence: 99%

H1/pAIM2 nanoparticles exert anti‐tumour effects that is associated with the inflammasome activation in renal carcinoma

Chai

Liu

et al. 2018

J Cellular Molecular Medi

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Renal cell carcinoma (RCC) is a high metastasis tumour with less effective treatment available currently. Absent in melanoma 2 (AIM2) as a tumour suppressor might be used as a potential therapeutic target for RCC treatment. Here, we found that AIM2 expression was significantly decreased in RCC patient specimens and renal carcinoma cell lines (786‐O and OSRC‐2). To establish a safe and effective AIM2 gene delivery system, we formed the nanoparticles consisting of a folate grafted PEI600‐CyD (H1) nanoparticle‐mediated AIM2 gene (H1/pAIM2) as an effective delivery agent. Delivery of H1/pAIM2 in renal carcinoma cells could remarkably increase the expression of AIM2, and subsequently decrease cell proliferation, migration, and invasion as well as enhance cell apoptosis. In order to evaluate the therapeutic efficacy of AIM2 in vivo, H1/pAIM2 nanoparticles were injected intratumorally into 786‐O‐xenograft mice. Administration of H1/pAIM2 nanoparticles could inhibit the tumour growth as evidenced by reduced tumour volume and weight. Furthermore, Blockade of inflammasome activation triggered by H1/pAIM2 nanoparticles using inflammasome inhibitor YVAD‐CMK abrogated the anti‐tumoral activities of H1/AIM2. These results indicated the therapeutic effect of H1/pAIM2 nanoparticles was mainly attributable to its capability to enhance the inflammasome activation. H1/AIM2 nanoparticles might act as an efficient therapeutic approach for RCC treatment.

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Harnessing Tumor Microenvironment for Nanoparticle‐Mediated Radiotherapy

Zhu

Zhao

2018

Advanced Therapeutics

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Recent years have witnessed the dramatic improvement of nanoparticle‐mediated radiotherapy in preclinical or even clinical cancer research. Among the extensive developments, tumor‐targeted strategies are receiving more and more attention as they become able increase their therapeutic effects as well as reduce the side effects to healthy tissues. The tumor microenvironment (TME) with its critical function in tumor development and distinctive abnormal characteristics, is also widely studied as a target/response for tumor‐specific nano‐radiotherapy. The fast advances of TME‐assisted nano‐radiotherapy have offered numerous novel strategies and approaches for efficiently destroying cancer. This review summarizes the recent advances and development of TME‐enabled nanoparticle‐mediated radiotherapy. Firstly, a brief description of the typical TME characteristics including vasculature, hypoxia, mild acidity, redox reactions, extracellular matrix, and various cellular components is given. Next, the representative examples of TME‐enabled nanoparticle‐mediated radiotherapy are categorized and discussed in two parts: TME components–targeted nano‐radiotherapy and TME characteristics‐responsive nano‐radiotherapy. Lastly, some obstacles and challenges associated with this field are also proposed at the end of this review.

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H1/pHGFK1 nanoparticles exert anti-tumoural and radiosensitising effects by inhibition of MET in glioblastoma

Abstract: H1/pHGFK1 exerts anti-tumoural and radiosensitive activities mainly through the inhibition and reversal of IR-induced MET and ATM-Chk2 axis activities in glioblastoma. H1/pHGFK1 nanoparticles are a potential radiosensitiser and angiogenic inhibitor for glioblastoma treatment.

Cited by 18 publications

References 43 publications

Combining DNA Vaccine and AIM2 in H1 Nanoparticles Exert Anti-Renal Carcinoma Effects via Enhancing Tumor-Specific Multi-functional CD8+ T-cell Responses

Combining DNA Vaccine and AIM2 in H1 Nanoparticles Exert Anti-Renal Carcinoma Effects via Enhancing Tumor-Specific Multi-functional CD8+ T-cell Responses

H1/pAIM2 nanoparticles exert anti‐tumour effects that is associated with the inflammasome activation in renal carcinoma

Harnessing Tumor Microenvironment for Nanoparticle‐Mediated Radiotherapy

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