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Featured researches published by Zixi Hu.


Nanoscale Research Letters | 2016

Aptamer-Functionalized Fluorescent Silica Nanoparticles for Highly Sensitive Detection of Leukemia Cells.

Juntao Tan; Nuo Yang; Zixi Hu; Jing Su; Jian-Hong Zhong; Yang Yang; Yating Yu; Jianmeng Zhu; Dabin Xue; Yingying Huang; Zongqiang Lai; Yong Huang; Xiaoling Lu; Yongxiang Zhao

A simple, highly sensitive method to detect leukemia cells has been developed based on aptamer-modified fluorescent silica nanoparticles (FSNPs). In this strategy, the amine-labeled Sgc8 aptamer was conjugated to carboxyl-modified FSNPs via amide coupling between amino and carboxyl groups. Sensitivity and specificity of Sgc8-FSNPs were assessed using flow cytometry and fluorescence microscopy. These results showed that Sgc8-FSNPs detected leukemia cells with high sensitivity and specificity. Aptamer-modified FSNPs hold promise for sensitive and specific detection of leukemia cells. Changing the aptamer may allow the FSNPs to detect other types of cancer cells.


Oncology Reports | 2017

An ‘activatable’ aptamer-based fluorescence probe for the detection of HepG2 cells

Zongqiang Lai; Juntao Tan; Ruirong Wan; Jie Tan; Zhenghua Zhang; Zixi Hu; Jieping Li; Wei Yang; Yiwei Wang; Yafeng Jiang; Jian He; Nuo Yang; Xiaoling Lu; Yongxiang Zhao

It is significant to develop a probe with sensitivity and specificity for the detection of cancer cells. The present study aimed to develop an ‘activatable’ aptamer-based fluorescence probe (AAFP) to detect cancer cells and frozen cancer tissue. This AAFP consisted of two fragments: aptamer TLS11a that targets HepG2 cells, and two short extending complementary DNA sequences with a 5′- and 3′-terminus that make the aptamer in hairpin structure a capable quencher to fluorophore. The ability of the AAFP to bind specifically to cancer cells was assessed using flow cytometry, fluorescence spectroscopy and fluorescence microscopy. Its ability to bind to frozen cancer tissue was assessed using fluorescence microscopy. As a result, in the absence of cancer cells, AAFP showed minimal fluorescence, reflecting auto-quenching. In the presence of cancer cells, however, AAFP showed a strong fluorescent signal. Therefore, this AAFP may be a promising tool for sensitive and specific detection of cancer.


Nanoscale Research Letters | 2017

Aptamer Combined with Fluorescent Silica Nanoparticles for Detection of Hepatoma Cells

Zixi Hu; Juntao Tan; Zongqiang Lai; Rong Zheng; Jian-Hong Zhong; Yiwei Wang; Xiaoxue Li; Nuo Yang; Jieping Li; Wei Yang; Yong Huang; Yongxiang Zhao; Xiaoling Lu

PurposeThe purpose of this study is to develop a simple, effective method to label hepatoma cells with aptamers and then detect them using fluorescent silica nanoparticles (FSNPs).MethodStreptavidin was conjugated to carboxyl-modified fluorescein isothiocyanate (FITC)-doped silica nanoparticles which were prepared by the reverse microemulsion method. The resulting streptavidin-conjugated fluorescent silica nanoparticles (SA-FSNPs) were mixed with hepatoma cells that had been labeled with biotin-conjugated aptamer TLS11a (Bio-TLS11a). The specificity and sensitivity of the nanoprobes were assessed using flow cytometry and fluorescence microscopy. Their toxicity was assessed in normal human liver cell cultures using the MTT assay, as well as in nude mice using immunohistochemistry.ResultsSA-FSNPs showed uniform size and shape, and fluorescence properties of them was similar to the free FITC dye. SA-FSNPs were able to detect aptamer-labeled hepatoma cells with excellent specificity and good sensitivity, and they emitted strong, photobleach-resistant fluorescent signal. SA-FSNPs showed no significant toxic effects in vitro or in vivo.ConclusionThe combination of biotin-conjugated aptamers and SA-FSNPs shows promise for sensitive detection of hepatoma cells, and potentially of other tumor cell types as well.


Theranostics | 2017

Mouse IP-10 Gene Delivered by Folate-modified Chitosan Nanoparticles and Dendritic/tumor Cells Fusion Vaccine Effectively Inhibit the Growth of Hepatocellular Carcinoma in Mice

Zixi Hu; Jiaojiao Chen; Sufang Zhou; Nuo Yang; Siliang Duan; Zhenghua Zhang; Jing Su; Jian He; Zhiyong Zhang; Xiaoling Lu; Yongxiang Zhao

Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells. The combination of FA-chitosan/mIP-10 and DC/tumor cell fusion vaccine against hepatocellular carcinoma (HCC) effectively inhibited the growth of implanted HCC tumors and prolonged the survival of mice. The combination therapy significantly reduced myeloid-derived suppressor cells (MDSC) in mouse spleen, local tumor, and bone marrow while increasing tumor-specific IFN-γ responses. Furthermore, the combination therapy significantly inhibited tumor cell proliferation while promoting their apoptosis. Taken together, our data illustrate that the mIP-10 enhances the anti-tumor effect of DC/tumor cell fusion vaccine by alleviating the immunosuppressive tumor environment.


Theranostics | 2018

The enhanced antitumor-specific immune response with mannose- and CpG-ODN-coated liposomes delivering TRP2 peptide

Chunhui Lai; Siliang Duan; Fang Ye; Xiaoqiong Hou; Xi Li; Jin Zhao; Xia Yu; Zixi Hu; Zhuoran Tang; Fengzhen Mo; Xiaomei Yang; Xiaoling Lu

Purpose: Dendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo. Methods: We developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2180-188 peptide as liposomal vaccine. M/CpG-ODN-TRP2-Lipo treatment was used to intendedly induce activation of DCs and antitumor- specific immune response in vivo. Results: Our results demonstrated in vitro that the prepared liposomal particles were efficiently taken up by DCs. This uptake led to an enhanced activation of DCs, as measured by the upregulation of MHC II, CD80, and CD86. Furthermore, M/CpG-ODN-TRP2-Lipo effectively inhibited the growth of implanted B16 melanoma and prolonged the survival of mice. This therapy significantly reduced the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells, while simultaneously increasing the number of activated T cells, tumor antigen-specific CD8+ cytotoxic T cells, and interferon-γ-producing cells. At the same time, it was found to suppress tumor angiogenesis and tumor cell proliferation, as well as up-regulate their apoptosis. Interestingly, MyD88-knockout mice had significantly shorter median survival times compared to wild-type mice following the administration of M/CpG-ODN-TRP2-Lipo. Conclusions: The results suggested that the antitumor activities of the vaccine partially rely on the Myd88 signaling pathway. Interestingly, compared to whole tumor cell lysate-based vaccine, M/CpG-ODN-TRP2-Lipo, tumor specific antigen peptide-based vaccine, improved survival of tumor-bearing mice as well as enhanced their antitumor responses. All in all, we describe a novel vaccine formulation, M/CpG-ODN-TRP2-Lipo, with the aim of improving antitumor responses by alleviating the immunosuppressive environment in tumors.


Scientific Reports | 2017

Fusions of Tumor-derived Endothelial Cells with Dendritic Cells Induces Antitumor Immunity

Yingying Huang; Qiqi Mao; Jian He; Jing Su; Yi Peng; Wei Liang; Zixi Hu; Sufang Zhou; Xiaoling Lu; Yongxiang Zhao

To explore dendritic cells/tumor-derived endothelial cells (DC/EC) fusion cells are potent stimulators of T cells to impact tumor progression. ECs were isolated from mice hepatoma cell line (H22) Xenograft, and dendritic cells were isolated from bone marrow of BALB/c mice, then the isolated ECs were cultured and detected the endothelial surface expression of CD105 by flow cytometry. The endothelial characteristics of ECs were detected by tube formation assay and Dil-Ac-LDL uptake assay. After the fusion with polyethylene glycol (PEG), we used DCs, ECs, DCs mixed ECs as the control groups, DC/EC fusion cells as the experimental group, Secretion of IFN-α and IFN-γ was evaluated, T lymphocyte proliferation and cytotoxic T lymphocytes (CTL) were detected in vitro. In vivo, T lymphocyte induced by five groups was injected to detect the effect of tumor progression. Purified ECs (CD105+) took the function of endothelial cells, then successfully fused with DCs. The DC/EC fusion cells were functional in stimulating the proliferation of T cells, which produced IFN-α and IFN-γ. In vivo, T cells stimulated by DC/EC fusion cells effectively repressed tumor growth. The fusion cells, which was capable of stimulating T cells, is indispensable for antitumor immunity.


Journal of Nanoscience and Nanotechnology | 2018

Graphene-Based Multifunctional Nanomaterials in Cancer Detection and Therapeutics

Wenlin Gong; Zixi Hu; Ying Liang; Yiwei Wang; Rong Zheng; Juntao Tan; Zongqiang Lai; Xiaoxue Li; Jieping Li; Xiaoling Lu; Yongxiang Zhao

Nanotechnology for early diagnosis and treatment of malignant tumor is a forefront topic in the international field of biotechnology and medicine. In order to improve the effect of cancer therapy, the timely and accurate detection of the cancer is important and necessary. Graphene and its derivatives have various excellent characteristics. For example, biological sensors based on graphene are good at amplifying detection signals, and its derivatives play an important role in the early diagnosis and cancer therapy. In view of this, we discussed the biological sensor application based on graphene and its derivatives in the detection and therapy of cancer.


Oncology Reports | 2017

Screening and antitumor effect of an anti‑CTLA‑4 nanobody

Ruirong Wan; Aiqun Liu; Xiaoqiong Hou; Zongqiang Lai; Jieping Li; Nuo Yang; Juntao Tan; Fengzhen Mo; Zixi Hu; Xiaomei Yang; Yongxiang Zhao; Xiaoling Lu

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a critical negative regulator of immune responses. CTLA-4 is rapidly upregulated following T-cell activation, and then binds to B7 molecules with a higher affinity than CD28. CTLA-4 may abolish the initiation of the responses of T cells by raising the threshold of signals required for full activation of T cells, and it also may terminate ongoing T-cell responses. This regulatory role has led to the development of monoclonal antibodies (mAbs) designed to block CTLA-4 activity for enhancing immune responses against cancer. mAbs have several disadvantages including high production cost and unstable behavior. Nanobodies (Nbs) are single-domain antigen-binding fragments derived from the camelid heavy-chain antibodies, which are highly attractive in cancer immunotherapy due to their small size, high specificity, and stability. We selected CTLA-4-specific Nbs from a high quality dromedary camel immune library by phage display technology. Four positive colonies were sequenced and classified based on the amino acids sequences in the CDR3 region. These Nbs recognized unique epitopes on CTLA-4 and displayed high binding rates when used on PHA-stimulated human T cells. Treatment of B16 melanoma-bearing C57BL/6 mice with anti-CTLA-4 nanobody 16 (Nb16) delayed melanoma growth and prolonged the survival time of mice. These data indicate that anti-CTLA-4 Nbs selected from a high quality phage display library may be effective for the treatment of patients with tumors.


Oncology Reports | 2016

A novel method for endothelial cell isolation

Qiqi Mao; Xianing Huang; Jian He; Wei Liang; Yi Peng; Jing Su; Yingying Huang; Zixi Hu; Xiaoling Lu; Yongxiang Zhao

The present study aimed to develop a quick and efficient method for purification of newborn endothelial cells from tumor tissues. Fresh tissues were separated from C57BL/6 mice bearing tumors derived from mouse lung cancer Lewis cells, fully minced and divided into two parts. One part was subjected to collagenase type I digestion with a vortex to form a single-cell suspension, while another part was digested but without a vortex. Then, the CD105+ cells were isolated using anti-CD105 antibody-coated Dynabeads. The isolated CD105+ cells were grown in culture medium and examined for the surface expression of CD105 by a fluorescence-activated cell sorter (FACS). The uptake of acetylated LDL and the ability to maintain capillary tube-like structure formation in the CD105+ cells were also examined by Dil-Ac-LDL uptake assay and tube formation assay. The expression of tumor newborn endothelial cells (CD105+) was tested in Lewis xenografts by immunohistochemistry. The number of cells which were obtained by the digestion process with a vortex was 5.70±0.23x10(4) much higher than the number without a vortex (0.32±0.04x10(4)) (P<0.01). The purity of CD105+ cell digestion with a vortex was significantly higher than that without a vortex. Dil-Ac-LDL uptake assay and tube formation assay confirmed that the CD105+ cells digested with a vortex exhibited typical functions of endothelial cells. In conclusion, the CD105+ cells isolated by the new method had high purity and displayed features of vascular endothelial cells. The modified method provides CD105+ cells with superior conditions for mechanistic research on the development of vessel-based disease.


Journal of Nanoscience and Nanotechnology | 2018

Recent Progress of Wnt Pathway Inhibitor Dickkopf-1 in Liver Cancer

Jieping Li; Wenlin Gong; Xiaoxue Li; Ruirong Wan; Fengzhen Mo; Zhenghua Zhang; Panpan Huang; Zixi Hu; Zongqiang Lai; Xiaoling Lu; Yongxiang Zhao

Hepatocellular carcinoma (HCC) is one of the most common cancers around the world. Multiple etiologic factors such as virus and environment can lead to HCC. It is a challenge for us to successfully detect early HCC due to the lack of effective characterized and specific biomarkers. However, if the early diagnosis is successfully realized, it provides crucial chance for HCC patients to receive effective treatment as early as possible. Dickkopf-1 (DKK-1) is a secretary glycoprotein, which negatively regulates Wnt pathway through binding to surface receptors LRP5/6 and Kremen 1/2. The expression of DKK-1 is regulated by p53, V-Myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), β-catenin, etc. Ectopic expression of DKK-1 can inhibit cell proliferation, or induce apoptosis with apoptosis enhancing factors. DKK-1 is low-expressed in many tumors, but overexpressed in others. Growing evidences show that DKK-1 plays complex and different roles in tumorigenesis, tumor progression and metastasis of different cancers. We herein review the recent progress in the expression and function of DKK-1 in hepatocellular carcinoma.

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Xiaoling Lu

Guangxi Medical University

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Yongxiang Zhao

Guangxi Medical University

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Zongqiang Lai

Guangxi Medical University

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Jian He

Guangxi Medical University

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Nuo Yang

Guangxi Medical University

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Yiwei Wang

Guangxi Medical University

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Juntao Tan

Guangxi Medical University

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Yong Huang

Guangxi Medical University

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Fengzhen Mo

Guangxi Medical University

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Jieping Li

Guangxi Medical University

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