TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
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2018
·Vol. 17
·期 7
·1379-1384
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IF 0.444
Jianfeng Quan,Yanli Zhao
Purpose: To investigate the anti-tumor effects of nedaplatin (NDP) and CpG oligodeoxynucleotide (CpG-ODN) combination therapy in a mouse-modeled lung cancer.Methods: To evaluate the anti-tumor effects of NDP and CpG-ODN combination therapy, a lung cancer xenograft mouse model was established by subcutaneous injection of LA-795 cells. BALB/c mice were divided into four groups as follows: NDP, CpG-, NDP + CpG-ODN and untreated control group. The sections of lung cancer tissue were stained with hematoxylin and eosin (H&E) and morphologically examined. Spleen, body weight, and spleen index were measured. Flow cytometry was used to determine the proportions of CD3+, CD8+, CD4+ and CD4+/CD8+ in mice blood cells. Serum levels of interferon-γ (IFN-γ) and interleukin-12 (IL-12) were measured by enzyme-linked immunosorbent assay (ELISA).Results: NDP + CpG-ODN therapy significantly reduced tumor volume and prolonged the survival time of tumor-bearing mice. NDP + CpG-ODN induced a change in cancer cell morphology, including large areas of necrosis which correlated with a reduction in tumor size. NDP + CpG-ODN significantly increased spleen weight/index and dramatically enhanced immune cell activation. This was evident in the increase serum levels of IFN-γ and IL-12.Conclusion: NDP and CpG-ODN combination therapy inhibits the growth of lung cancer and prolongs the survival time of tumor-bearing mice. This may result from the activation of immune cells and increased expression of IFN-γ and IL-12.Keywords: CpG ODN, NDP, Lung cancer, Combination therapy
研究领域:
肿瘤学
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免疫学
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DOI
高影响因子
Nanoscale
·
2017
·Vol. 9
·期 37
·14236-14247
·
IF 7.367
Zhenzhen Wang,Yan Zhang,Zhen Liu,Kai Dong,Chaoqun Liu,Xiang Ran,Fang Pu,Enguo Ju,Jinsong Ren,Xiaogang Qu
Unmethylated cytosine-phosphate-guanine (CpG) oligonucleotides (ODNs) possess high immunostimulatory activity and represent attractive tools for cancer treatment. However, their success in eliminating large solid tumors was hampered by the immunosuppressive tumor microenvironment. Herein, we report that the design of a novel MnO2–CpG–silver nanoclusters (AgNCs)–doxorubicin (DOX) conjugate for enhanced cancer immunotherapy, in which MnO2 nanosheets function as unique supports to integrate the chemotherapy drug DOX and the immunotherapeutic agent CpG–AgNCs. Importantly, DOX could be conjugated with MnO2 nanosheets through π–π interactions to serve as a bifunctional modulator of the tumor microenvironment to activate a tumor-specific immune response by inducing immunogenic cell death, and reverse the immunosuppressive tumor microenvironment via abrogating the immune-suppressive activity of regulatory T cells, both of which would greatly improve the immune response of CpG–AgNCs. In this way, the T-cell immune responses of CpG–AgNCs which are linked to MnO2 nanosheets were significantly enhanced and could exhibit remarkable antitumor activity against large solid tumors. Our study may guide the rational design of immunotherapeutic boosters for improving cancer treatment.
研究领域:
肿瘤学
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纳米医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Qingming Bao,Mingming Bao,Hai Xiao,Tsogzolmaa Ganbold,Shuqin Han,Huricha Baigude
The simultaneous delivery of CpG oligonucleotide along with short interfering RNA (siRNA) has the potential to significantly boost the anticancer impact of siRNA medications. Our previous research demonstrated that Curdlan nanoparticles functionalized with adenosine are capable of selectively delivering therapeutic siRNA to cancerous cells through endocytosis mediated by adenosine receptors. Herein, we synthesized a dual-ligand-functionalized Curdlan polymer (denoted by CuMAN) to simultaneously target tumor cells and tumor-associated macrophages (TAMs). CuMAN nanoparticles containing CpG and siRNA demonstrated enhanced uptake by B16F10 tumor cells and bone marrow-derived macrophages, which are facilitated by AR on tumor cells and mannose receptor on macrophages. This led to increased release of pro-inflammatory cytokines in both in vitro and in vivo settings. The synergistic effect of CpG on TAMs and RNAi on tumor cells mediated by the CuMAN nanoparticle not only suppressed the tumor growth but also strongly inhibited the lung metastasis. Our findings indicate that the CuMAN nanoparticle has potential as an effective dual-targeting delivery system for nucleic acid therapeutics.
研究领域:
生物医学工程
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肿瘤免疫学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2024
·Vol. 26
·期 2
·1-13
·
IF 2.1
Ye Haiyang,Zhang Li,Qiu Xiaonan,Qiu Jianghong,Xu Wenqing,Xu Xiao,Yu Huijun,Zou Shengqiang,Du Fengyi,Zheng Guojun,Wu Yunchao
Photothermal therapy (PTT) can kill the tumor in situ, but fail to trigger strong antitumor immune response against its recurrence and metastasis. Herein, mannose-grafting Fe-doped carbon dots (M/Fe-CDs) were prepared via hydrothermal carbonization and chemical modification. The prepared M/Fe-CDs had characteristics of excellent optical qualities, good water solubility, and outstanding biocompatibility. Compared with pure CDs, the doping of Fe atom endowed the M/Fe-CDs with a high photothermal conversion efficiency (from 12.1 up to 30.1%). Under 808-nm NIR irradiation, the M/Fe-CDs could lead to local hyperthermia to kill tumor cells. Importantly, the M/Fe-CDs were capable of loading CpG-ODNs via electrostatic absorption and delivering them into the cytoplasm of dendritic cells (DCs). Finally, the CpG-ODNs-loading M/Fe-CDs could significantly increase the CD80/86 expression on the DCs surface. These results demonstrated that the M/Fe-CDs could be used as a versatile nanoplatform to combine the PTT and immune activation for tumor treatment.
研究领域:
生物医学工程
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肿瘤免疫学
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纳米医学
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产品关联
DOI
高影响因子
Communications Biology
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2020
·Vol. 3
·期 1
·1-12
·
IF 4.165
Zhou Lulu,Chen Lv,Hu Xiaochun,Lu Yonglin,Liu Wenjie,Sun Yanting,Yao Tianming,Dong Chunyan,Shi Shuo
Despite its great potential in cancer therapy, phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), often cause metastasis of tumors. Immunotherapy has revolutionized the cancer treatment owing to the capability of activating immune system to eliminate tumors. However, the integration of phototherapy and immunotherapy in a single nanoagent for cancer therapy is still a challenging task. Here, we fabricated (Cu 9 S 5 @mSiO 2 -PpIX@MnO 2 @CpG (CSPM@CpG)) as a synergistic therapeutic model for phototherapy enhanced immunotherapy. The intracellular uptake of cytosine-phosphate-guanine (CpG) promoted the infiltration of cytotoxic T lymphocytes (CTLs) in tumor tissue, further stimulating the production of interferon gamma (IFN-γ) and remarkably elevating the immune response level. Excellent anti-tumor effects have been achieved by synergistic PTT/PDT/immunotherapy. The metastasis of tumors was effectively inhibited by the immune response of CpG. Thus, our proposed work provides a strategy to combine phototherapy with immunotherapy to enhance the therapeutic efficiency and further inhibit metastasis of tumors.
研究领域:
癌症治疗
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纳米技术
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免疫学
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光疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2015
·Vol. 10
·期 10
·e0140265
·
IF 3.234
Hengrui Zheng,Songsong Wen,Yang Zhang,Zhenliang Sun
Cytosine–guanine (CpG) containing oligodeoxynucleotides (ODN) have significant clinical potential as immunotherapeutics. However, limitations exist due to their transient biological stability in vivo , lack of specificity for target cells, and poor cellular uptake. To address these issues, we prepared amine magnetic mesoporous silica nanoparticles (M-MSN-A) then further modified with polyethylene glycol (PEG) for use as CpG delivery vectors. The PEG modified M-MSN-A (M-MSN-P) had notable CpG ODN loading capacity, negligible cytotoxicity, and were easily internalized into cells where they released the loaded CpG into the cytoplasm. As a result, such complexes were effective in activating macrophages and inhibiting tumor cells when combined with chemotherapeutics in vitro . Furthermore, these complexes had excellent immuno-stimulating activity in vivo , compared to the free CpG therapeutics. We report here a highly effective MSNs-based delivery system with great potential as a therapeutic CpG formulation in cancer immunotherapy.
研究领域:
生物材料学
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免疫学
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2022
·
IF 7.033
Fenfen Gu,Chuling Hu,Wei Cao,Chao Li,Qingming Xia,Yuan Gao,Yan Liu,Shen Gao
Introduction Currently, the main treatment for advanced breast cancer is still chemotherapy. Immunological and chemical combination therapy has a coordinated therapeutic effect and achieves some efficacy. However, the immunosuppressive tumor microenvironment is a major cause for the failure of immunotherapy in breast cancer. CpG oligodeoxynucleotides can activate the tumor immune microenvironment to reverse the failure of immunotherapy. Methods In this study, we designed an amphiphilic peptide micelle system (Co-LMs), which can targeted delivery of the immune adjuvant CpG and the chemotherapeutic drug doxorubicin to breast cancer tumors simultaneously. The peptide micelle system achieved tumor microenvironment pH and redox-sensitive drug release. Results and Discussion Co-LMs showed 2.3 times the antitumor efficacy of chemotherapy alone and 5.1 times the antitumor efficacy of immunotherapy alone in triple-negative breast cancer mice. Co-LMs activated cytotoxic CD8+ T lymphocytes and CD4+ T cells in mice to a greater extent than single treatments. We also found that Co-LMs inhibited the metastasis of circulating tumor cells in the bloodstream to some extent. These results indicate that the Co-LMs offer a promising therapeutic strategy against triple-negative breast cancer.
研究领域:
肿瘤学
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药剂学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2025
·
IF 4.1
Shiwen Zhang,Changqiang Wang,Jing Jiang,Linlu Li,Jiaqi Luo,Jingying Zhu,Renxu Chen
Background Immune escape of tumor cells is a common problem with tumor photothermal therapy utilizing gold nanorods (Au NRs). Whether CpG ODN, an immune adjuvant, can synergize with Au NRs to activate the immune response and its potential mechanism is not clear.Methods The effect of Au NRs combined with CpG ODN (Au NRs-C) on the activity of various immune-related cells, such as double-positive T cells, macrophages, NK cells, Th17, and Treg. The expression levels of various immune and inflammation-related factors, such as IL-1R1, IL-6, IL-17, and TNF-α were characterized. Transcriptome sequencing analysis was used to explore the potential immunomodulatory mechanisms of Au NRs-C. Whether immune activation was enhanced by antibody-functionalized Au NR upon binding to CpG ODN was assessed.Results Flow cytometry and ELISA analyses indicate that both Au NRs and CpG ODN increase pro-inflammatory cytokine levels and immune activation. However, Au NRs-C demonstrated superior immune activation potential. Furthermore, Au NRs stimulate the expression of Treg, while Au NRs-C significantly inhibit this effect. This suggests that the conjugation of CpG ODN with Au NRs not only greatly enhances the immune activation but also compensates for some of their deficiencies in eliciting immune responses. Transcriptome sequencing uncovered DEGs mainly localized to immune and pro-inflammatory cytokine pathways. PPI analysis identified six hub genes: FOXM1, HMOX1, UBE2C, E2F1, PECAM1, and FCGR3A. Moreover, CpG conjugation with antibody functionalization- Au NRs enhances immune stimulation.Conclusion Au NRs-C promotes immune activation by eliciting changes in the activity of immune-associated cells and expression of inflammatory factors through multiple pathways, such as MHC antigen presentation and Toll-like receptor-mediated immune processes.
研究领域:
免疫学
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纳米医学
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癌症生物学
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生物信息学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Genetics
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2021
·
IF 4.599
Peng Yi,Xiongfeng Xu,Jiawei Yao,Bo Qiu
Objectives Transcriptional changes in cartilage can impact function by causing degradation such as that which occurs during the development of osteoarthritis (OA). Epigenetic regulation may be a key factor leading to transcriptional changes in OA. In this study, we performed a combined analysis of DNA methylation and gene expression microarray datasets and identified key transcription factors (TFs) central to the regulation of gene expression in OA. Methods A DNA methylation profile dataset (GSE63106) and a gene expression profiling dataset (GSE114007) were extracted from the Gene Expression Omnibus (GEO). We used ChAMP methylation analysis and the Limma package to identify differentially methylation genes (DMGs) and differentially expressed genes (DEGs) from normal and human knee cartilage samples in OA. Function enrichment analysis of DMGs was conducted using the DAVID database. A combined analysis of DEGs and DMGs was conducted to identify key TFs in OA. We then validated the mRNA expression of selected TFs in normal and OA cartilage by RT-qPCR. Primary chondrocytes were cultured and treated with the DNA methylation inhibitor 5-Aza-2-deoxycytidine (5-Aza) for functional validation. Results We identified 2,170 differential methylation sites (DMS) containing 1005 genes and 1986 DEGs between normal human and OA cartilage. Functional analysis of DMGs revealed that focal adhesion, extracellular matrix (ECM)-receptor interactions, the PI3K-Akt signaling pathway, and the FoxO signaling pathway were involved in OA. Integrated analysis showed a subset of 17 TFs. Four TFs (ELF3, SOX11, RARA, and FOXD2) were validated. RT-qPCR results showed the mRNA expression of SOX11, RARA, and FOXD2 were consistent with the results from the mRNA expression data. However, the expression of ELF3 could not be validated. Upon 5-Aza-2′-deoxycytidine (5-Aza) treatment, the mRNA levels of ELF3 and SOX11 were down-regulated, whilst RARA was up-regulated, and FOXD2 showed no significant change in expression level. Conclusions the effect of DNA methylation on the transcriptional regulation is related to the distribution of methylated sites across the genome. Epigenetic studies on the positions of DMS in transcriptional units can inform a better understanding of the function of DNA methylation and its transcription regulation.
研究领域:
分子生物学
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表观遗传学
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风湿病学
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骨关节炎研究
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转录调控
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生物信息学
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软骨生物学
✓ 已验证
DOI
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
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2021
·
IF 2.231
Mi Ou,Kunci Chen,Dandan Gao,Yanduo Wu,Qing Luo,Haiyang Liu,Jian Zhao
Dmrt1 is an important transcriptional regulator that plays critical role in male gonadogenesis, testicular differentiation and development. In this study, Dmrt1 was cloned from blotched snakehead ( Channa maculata ) , which is designated as CmDmrt1 . Cm Dmrt1 encoded a putative protein with 293 amino acids and presented an extremely conserved DM domain. It was nearly expressed in the gonads, and the expression was more than 15 times higher in the testis than in the ovary. 1851 bp promoter sequence of CmDmrt1 was characterized and the methylation levels of the CpG sites were analyzed to detect sex-related differences. A significant negative correlation between CmDmrt1 expression and CpG methylation level of its promoter was found in the testis and ovary. During gonadal development, CmDmrt1 transcription displayed strong male-biased expression patterns, increased with the maturation of testis and reached the peak at 195 days after hatching (dah), which indicates a significant role of Dmrt1 in spermatogenesis. Steroid treatment could influence CmDmrt1 expression, and long-term 17β-estradiol (E2) treatment could induce the male-to-female secondary sex reversal (SSR), which resulted in the differentiated testis transformed to ovary or ovotestis. Meanwhile, CmDmrt1 expression was down-regulated to fairly low level in the ovary of the SSR XY fish, which was similar to that in normal XX females ovary. Our research illustrates that Dmrt1 is linked to testis differentiation and spermatogenesis in blotched snakehead, providing information for functional studies on sex differentiation and gonadal development of C. maculata , and scientific basis for the production practice of all-male snakehead breeding.
研究领域:
分子生物学
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发育生物学
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水产养殖
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遗传学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-14
·
IF 9.429
Deng Bo,Ma Bing,Ma Yingying,Cao Pei,Leng Xigang,Huang Pengyu,Zhao Yuanyuan,Ji Tianjiao,Lu Xueguang,Liu Lanxia
Chemotherapeutics that can trigger immunogenic cell death (ICD) and release tumor-specific antigens are effective on treating a variety of cancers. The codelivery of chemotherapeutics with adjuvants is a promising strategy to achieve synergistic therapeutic effect. However, low drug loading and complicated preparation of current delivery systems lead to carrier-associated toxicity and immunogenicity. Herein, we developed a facile approach to construct liposomal spherical nucleic acids (SNA) by the self-assembly of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)-doxorubicin conjugate and DOPE-matrix metalloproteinases-9 (MMP-9) responsive peptide-CpG conjugate (DOPE-MMP-CpG). Liposomal SNAs efficiently co-delivered DOX and CpG into tumors and released the two drugs upon biological stimuli of MMP-9 enzyme in tumor microenvironment (TME) and high concentration of endogenous glutathione in tumor cells. We demonstrated that liposomal SNA enhanced activation of dendritic cells (DCs), promoted expansion of CD8 + and CD4 + T cells in both tumors and spleen, inhibited tumor growth, and extended animal survival. This work provided a simple strategy of delivering chemotherapeutics and adjuvants to tumors with synergistic therapeutic effect and reduced side effect. Graphical Abstract
研究领域:
癌症治疗
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药物递送系统
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免疫疗法
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纳米医学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Jing Wang,Nuli Xie,Shan Lu,Bo Xiao,Yangqin Ou,Qingnian Li,Dexian Liu,Wenhu Zhou
Intracerebral hemorrhage (ICH) presents a formidable challenge due to its high mortality and disability rates, primarily attributed to cerebral hematoma formation and ensuing neuroinflammation. Swift hematoma removal is paramount for prognosis, yet existing interventions carry risks and limitations. Notably, elevated CD47 expression on hematoma-associated RBC triggers a “don't eat me” signal, impeding hematoma clearance, while microglial/macrophage erythrophagocytosis exacerbates oxidative stress and the RBC lysate evokes neuroinflammation. To address this conundrum, a multifunctional nanomedicine (TD-CFR), employing DNA tetrahedra (TD) as a carrier for ICH treatment is introduced. The investigations reveal that CpG enhances the phagocytosis of CD47-expressing RBC by microglia/macrophages via lipid metabolism modulation. Integration of CpG into TD preserves its pro-phagocytic efficacy, while TD's double-stranded region enables efficient encapsulation of Rutin, a potent anti-inflammatory and antioxidant flavonoid. Capitalizing on disrupted blood-brain barrier integrity at the hemorrhage site, TD-CFR achieves robust enrichment within cerebral hematoma post-intravenous administration, augmented by folate receptor-mediated targeting of microglia/macrophages. Efficacy assessments in mouse and rabbit ICH models confirm TD-CFR's therapeutic benefits, including hematoma clearance, neuroinflammation suppression, and brain function restoration. Leveraging TD's high biosafety profile and dual active ingredient loading capacity, the study unveils a promising drug treatment paradigm for ICH.
研究领域:
神经科学
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药学
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）