ADVANCED MATERIALS
·
2025
·
IF 26.8
Quanwei Sun,Huiyu Lu,Wenshuo Yang,Zhengwei Song,Chen Chen,Xu Ruan,Min Luo,Yunlong Li,Huihui Li,Zexin Yang,Kang Liu,Wencui Shang,Yujing Xu,Qinghua Wu,Wei Shen,Ye Yang,Dengke Yin
Humoral immunity-cancer crosstalk has gained attention recently owing to its impact on tumor immune responses and therapy responsiveness. Here, it is shown that epithelial breast cancer cells can directly bind with non-antigen-specific IgA, dependent on polymeric immunoglobulin receptor (PIGR)-mediated transcytosis function, modulating tumoral inflammatory genes and sensitizing antitumor response. To harness this biology, a hybrid tumor vaccine is designed by covering the adjuvant-loaded cancer cell vesicles with a calcium phosphate shell, which retains the antigen information of the original tumor cells and exhibits robust mucosal adhesion in nasal tissues. Following intranasal vaccination, such a hybrid vaccine preferentially activates germinal center responses in nasal-associated lymphoid tissues and drives the production of tumoral antigen-specific IgA-dominated humoral immunity in both serum and lung through the property of “common mucosal immune system”, thus coordinating cellular immune responses to prevent lung colonization of IgA-opsonized breast cancer. In the inoperable and postoperative breast cancer model, intranasal vaccination with the hybrid vaccine also enables the amplification of the therapeutic benefits of local/systemic therapies. In summary, this work presents insights into the antitumor biology of IgA in epithelial breast cancer and explores a highly effective vaccine strategy focused on governing IgA-dominated humoral immunity to combat breast cancer, especially lung metastasis.
研究领域:
肿瘤学
·
免疫学
·
微生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
CANCER SCIENCE
·
2024
·
IF 4.5
Yuankun Chen,Gaofeng Pan,Yijun Yang,Haifeng Wu,Minhua Weng,Qiuping Wu,Yufeng Gao,Wenting Li
Cancer-associated fibroblasts (CAFs) are essential players in the tumor microenvironment (TME) due to their roles in facilitating tumor progression and metastasis. It is worth noting that the high-metastatic hepatocellular carcinoma (HCC) cell-derived exosomes have exhibited the ability to transform normal fibroblasts into CAFs, which further fosters the lung metastasis of low-metastatic HCC cells. Yet, the mechanisms underlying this tumor exosome-induced metastatic niche formation are poorly explored. In this study, the secreted protein arginyl aminopeptidase (RNPEP) was highly expressed in the plasma of patients with HCC. In addition, high-metastatic HCC cells showed augmented RNPEP expression levels in their exosomes. These exosomes induced obvious CAF-like properties in the human fibroblast cell line MRC-5, as evidenced by the increased CAF marker expression, and enhanced migratory ability. More strikingly, the secretions from high-metastatic tumor exosome-educated MRC-5 cells increased tumor stemness and promoted epithelial–mesenchymal transition (EMT) in MHCC-97L cells, a low-metastatic HCC cell line. However, the knockdown of RNPEP in exosomes from high-metastatic HCC cells abated the changes described above. Animal studies in vivo highlighted the pro-tumor and pro-metastatic effects of exosomal RNPEP on MHCC-97L cells by inducing CAF activation. Furthermore, tumor-derived exosomal RNPEP induced the activation of NF-κB signaling in MRC-5 cells, a critical pathway associated with CAF activation. Collectively, these results provide novel insight into tumor-derived exosomal RNPEP for its crosstalk with CAFs during HCC lung metastasis.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2021
·
IF 5.268
Hongyan Zhang,Ji Li,Rong Yuan,Yufen Li,Yue Zhang,Xiaoyun Hu,Jiqiang Qu,Yu Chen,Zheran Wang,Mingyu Xia,Dongkai Wang
Functionally-enabled delivery systems for aggressive lung metastases from breast cancer have been broadly examined, and the simultaneous inhibition of metastasis while fighting tumors persists as a provocative concern. We propose a valid strategy for delivering natural drugs-Honokiol (Hol) to achieve eradication of breast cancer cells and inhibition of pulmonary metastasis. A non-toxic degradable pH-sensitive polymer-PBAE for encapsulated Hol, and the outer layer was wrapped with Folate-DSPE-PEG 2000 (FA/PBAE/Hol-NPs), which have strengthened stability, prolonged in vivo circulation time and efficiently targets tumor sites. FA/PBAE/Hol-NPs displayed dampening the capability of migration and invasion, elevated 4T1 uptake and boosted apoptosis. What’s more, 4T1 breast cancer model mice exhibited marked anti-tumor (Inhibition rate of 62.8 %) and lung metastasis suppression (Inhibition rate of 84.3 %). In parallel, histological immunofluorescence and immunohistochemical assays demonstrate higher apoptosis levels and repression of matrix metalloproteinase expression in mice, all of which are instrumental in inhibiting lung metastasis. Taken together, FA/PBAE/Hol-NPs can as an efficacious intravenous drug delivery system for the curative treatment of metastatic breast cancer.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2020
·
IF 14.588
Yue Tan,Kui He,Bing Tang,Huarui Chen,Zhipeng Zhao,Chengqian Zhang,Li Lin,Jinbin Liu
The nanoprobes for identification of cancer metastases in the mononuclear phagocyte system (MPS) organs are of significant importance but are limited due to the long-standing challenge of low tumor-targeting specificity with inadequate targeting efficiency and high nonspecific accumulation. Here, we report a surface regulation strategy that integrates the tumor-acidity-activated charge-reversal behavior and precise control in both hydrodynamic diameter (HD) and surface charge on ultrasmall luminescent gold nanoparticles (AuNPs) to achieve significantly high tumor-targeting specificity. The precise regulation of AuNPs to a rational HD and surface charge could rapidly and selectively recognize small metastatic tumors (∼1 mm) in liver and lung with high signal-to-noise ratios of 4.6 and 4.5, respectively. These results help further understand the in vivo transport of nanoprobes and provide guidance for design of translatable nanosized nanomedicines in cancer metastasis theranostics.
研究领域:
纳米医学
·
肿瘤学
·
生物材料学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2022
·
IF 9.417
Yuqin Yang,Desheng Cai,Yisong Shu,Zhihua Yuan,Wenmin Pi,Yaozhi Zhang,Jihui Lu,Jingyi Jiao,Xuehao Cheng,Feifei Li,Penglong Wang,Haimin Lei
It is crucial to inhibit tumor growth and distant metastasis for breast cancer (BC) therapy. However, the treatment primarily dependent on surgery, chemotherapy, and radiotherapy is far from satisfactory. It had been demonstrated that the CXCL1/2-S100A8/9 axis played an essential role in BC therapy. Therefore, we constructed a natural product hydrogel for BC therapy by blocking CXCL1 signaling. The GK-GA (phytochemicals of Genkwa Flos -glycyrrhizic acid) hydrogel was designed in a one-step “green” approach. The pharmacodynamics study showed GK-GA exhibited significant anti-tumor and anti-lung metastasis activities, resulting in the inhibition rate of tumor growth (IRG) over 90 % at 6.25 mg·kg −1 , and did not display any obvious toxicity. In addition, the potent antitumor efficiency was also attributed to aggregation/assembly-induced retention (AIR) property. RNA sequencing analysis revealed the gene expression was significantly down-regulated in the GK-GA group, which were BCL2, CASP3, CXCL1, CXCL2, CXCR2, S100A8, S100A9, and confirmed further by western blot (WB). Our findings indicated natural product GK-GA hydrogel inhibited tumor growth and lung metastasis via the BCL2-CASP3 mitochondrial apoptosis pathway as well as the CXCL1/2-S100A8/9 pathway. This study provides inspiration for the fabrication of new excipients-free nano-dispersion in a one-step, no‐carrier‐added, organic solvent-free, “green” approach, particularly for small molecular antitumor agents.
研究领域:
肿瘤学
·
药学
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分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Enyang Yao,Yang Li,Kai Deng,Wei He,Milad Ashrafizadeh,João Conde,Liyu Yang
Osteosarcoma is the most common primary bone tumor with a high metastatic rate. Despite the improvement in patient prognosis with conventional therapeutics, enhancing the survival of patients with metastatic disease remains a challenge. Zoledronic acid (ZOL) stimulates apoptosis in cancer cells and is considered a promising drug for osteosarcoma therapy. Moreover, depletion of Inhibin Subunit Beta A (INHBA), a member of the transforming growth factor superfamily, can suppress osteosarcoma cell proliferation and invasion. Regarding the restricted potential of monotherapy, combination therapies, such as small interfering RNA (siRNA) and chemotherapy, are ideal strategies. However, off-target effects and adverse impacts lead to unsatisfactory clinical efficacy of these drugs. To address this challenge, we designed a folic acid-modified macrophage membrane coated with a carbon quantum dot (CQD) nanoplatform for the co-delivery of ZOL and siINHBA (ZOL-siINHBA@CQD@RM-FA). The anticancer activity of this nanotherapeutic agent was examined in vitro and in vivo . ZOL-siINHBA@CQD@RM-FA was approximately 200.7 nm in size, had a negative charge, excellent pH responsiveness, desirable biocompatibility, and high cellular uptake. This nanosystem achieved favorable co-delivery of ZOL/siINHBA and impaired osteosarcoma proliferation and invasion in vitro . Notably, intravenous administration facilitated tumor growth regression and inhibited lung metastasis without systemic toxicity. Accordingly, this nanotherapy could be considered an effective treatment for osteosarcoma, and the nanodelivery system shows potential for combined therapy by co-delivering genes and chemotherapy drugs.
研究领域:
肿瘤学
·
纳米医学
·
药物递送系统
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Benyue Sun,Wenwen Xie,Xuejiao Li,Taohua Liu,Jingjing Bai,Yuan Yao,Long Ma,Shuli Man
Inulin as a natural polysaccharide regulates intestinal microorganisms, and improves the immune and gastrointestinal function. In order to explore the effect of inulin on pulmonary metastasis of colon cancer, we set up a CT26 injected pulmonary metastatic model. The results showed that inulin used alone did not improve pulmonary metastasis of colon cancer, while inulin combined with rifaximin significantly prolonged the survival time of mice, and inhibited pulmonary metastasis compared with model and inulin groups. Inulin treatment increased the abundance of harmful bacteria such as Proteobacteria and Actinobacteria , while combined treatment decreased their abundance and increased the abundance of beneficial bacteria containing Firmicutes and Eubacterium which belonged to the bile acid-related bacteria. The combination treatment decreased the content of primary bile acids and secondary bile acids in the feces of mice, especial for DCA and LCA which were the agonists of TGR5. Furthermore, the combination treatment reduced the mRNA expression of the TGR5, cyclin dependent kinase 4, cyclin 1 and CDK2, increased the mRNA expression of p21 in the lung, down-regulated the level of NF-κB p65, and up-regulated the level of TNF-α compared with the model group. The above may be the reason for the better use of the combination treatment.
研究领域:
肿瘤学
·
微生物学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER RESEARCH
·
2024
·Vol. 84
·期 21
·3538-3555
·
IF 12.5
Wang Xinzhi,Qu Yi,Xu Qianqian,Jiang Zeyu,Wang Hang,Lin Binyan,Cao Zehong,Pan Yuqi,Li Sheng,Hu Yili,Yang Hui,He Li,Chang Hang,Hang Bo,Wen Hongmei,Wu Hao,Mao Jian-Hua
Metastasis to the lungs is a leading cause of death for patients with breast cancer. Therefore, effective therapies are urgently needed to prevent and treat lung metastasis. In this study, we uncovered a mechanism by which NAD(P)H:quinone oxidoreductase 1 (NQO1) orchestrates lung metastasis. NQO1 stabilized and upregulated peptidyl-prolyl cis-trans isomerase A (PPIA), a chaperone that regulates protein conformation and activity, by preventing its oxidation at a critical cysteine residue C161. PPIA subsequently activated CD147, a membrane protein that facilitates cell invasion. Moreover, NQO1-induced secretion of PPIA modulated the immune landscape of both primary and lung metastatic sites. Secreted PPIA engaged CD147 on neutrophils and triggered the release of neutrophil extracellular traps (NET) and neutrophil elastase, which enhanced tumor progression, invasiveness, and lung colonization. Pharmacological targeting of PPIA effectively inhibited NQO1-mediated breast cancer lung metastasis. These findings reveal a previously unrecognized NQO1-PPIA-CD147-NET axis that drives breast cancer lung metastasis. Inhibiting this axis is a potential therapeutic strategy to limit lung metastasis in patients with breast cancer. Significance: NQO1 stabilizes and promotes the secretion of PPIA to activate CD147 in neutrophils and stimulate NET formation, promoting breast cancer lung metastasis and providing therapeutic targets for this fatal condition.
研究领域:
癌症生物学
·
免疫学
·
分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF DRUG TARGETING
·
2023
·
IF 4.5
Shan Shi,Meiting Cao,Yang Li,Liping Zhou,Shurong Zhang,Xiaoyue Wang,Juan Xin,Wei Li
Lung metastatic breast cancer is a leading cause of cancer-related death in women and difficult to treat due to non-specific drug delivery. Herein a sequential targeting dual-responsive magnetic nanoparticle was fabricated, where Fe3O4 nanoparticle was used as magnetic core, then sequentially coated with tetraethyl orthosilicate, bis[3-(triethoxy-silyl)propyl] tetrasulfide, and 3-(trimethoxysilyl) propylmethacrylate to afford -C = C- on the surface for further polymerisation with acrylic acid, acryloyl-6-ethylenediamine-6-deoxy-β-cyclodextrin using N, N-bisacryloylcy- stamine as cross-linker, obtaining pH/redox dual-responsive magnetic nanoparticle (MNPs-CD) to delivery doxorubicin (DOX) for suppressing lung metastatic breast cancer. Our results suggested DOX-loaded nanoparticle could target the lung metastases site by sequential targeting, in which they first be delivered to the lung and even the metastatic nodules through size-driven, electrical interaction, and magnetic field-guided mechanisms, then be effectively internalised into the cancer cells followed by intelligently triggering DOX release. MTT analysis demonstrated DOX-loaded nanoparticle exhibited high anti-tumour activity against 4T1 and A549 cells. 4T1 tumour-bearing mice were employed to confirm the higher specific accumulation in lung and improved anti-metastatic therapy efficiency of DOX by focussing an extracorporeal magnetic field on the biological target. Our findings suggested the as-proposed dual-responsive magnetic nanoparticle offered a prerequisite to inhibit lung metastasis of breast cancer tumours.
研究领域:
肿瘤学
·
药剂学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Dandan Mi,Jiaojiao Li,Rujing Wang,Yuke Li,Lan Zou,Chen Sun,Shenao Yan,Huan Yang,Mengnan Zhao,Sanjun Shi
Surgical removal remains the predominant treatment strategy for triple-negative breast cancer (TNBC). However, risks that include high locoregional recurrence and remote metastasis threaten patient survival and quality of life after surgery. In this study, a hydrogel based on poly (ethylene glycol) dimethacrylate and sericin methacryloyl was fabricated by photopolymerization to fill the resection cavity and prevent recurrence. The obtained hydrogel exhibited mechanical properties compatible with breast tissue and facilitated postsurgical wound management by promoting tissue regeneration. The DNA methylation inhibitor decitabine (DEC) and poly (lactic- co -glycolic acid)-encapsulated phytochemical gambogic acid (GA) were loaded into the hydrogel. The as-prepared hydrogel promoted fast release of DEC and sustained release of GA, leading to gasdermin E -mediated tumor cell pyroptosis and activating antitumor immune responses. Inducing postsurgical tumor cell pyroptosis inhibited local tumor recurrence and lung metastasis . While the dual-drug-loaded hydrogel system cured less than half of tumor-bearing mice, the cured mice survived for over half a year. These findings indicate that our hydrogel system is an excellent biocompatible platform for postsurgical TNBC therapy.
研究领域:
肿瘤学
·
材料科学
·
生物医学工程
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR BIOCHEMISTRY
·
2023
·Vol. 124
·期 4
·557-572
·
IF 4
Juan Gu,Xu Chu,Yujia Huo,Chaoyi Liu,Qingge Chen,Shengnan Hu,Yanyan Pei,Pu Ding,Sen Pang,Ming Wang
Gastric cancer (GC) with pulmonary metastasis is one of the deadliest diseases in the world; however, the underlying pathological mechanisms and potential therapeutic targets remain to be elucidated. As exosomes play indispensable roles in the formation of premetastatic niches (PMN) and cancer metastasis. Therefore, investigating the underlying mechanisms of exosome-mediated pulmonary metastasis of GC may shed new light on identifying novel therapeutic targets for GC treatment. GC-derived exosomes were isolated from the conditioned medium of mouse forestomach carcinoma (MFC) cell line. The effects of MFC-derived exosomes on pulmonary macrophage polarization were analyzed by reverse- transcription polymerase chain reaction and flow cytometry. Expression of PD-L1 and other proteins was evaluated by Western blot. Exosomal microRNAs (miRNAs) were analyzed by microarray. GC-derived exosomes (GC-exo) accumulated in high numbers in the lungs and were ingested by macrophages. The extracellular-signal-regulated kinase (ERK) signaling pathway was activated by GC-exo, inducing macrophage immunosuppressive-phenotype differentiation and increased PD-L1 expression. miRNA-sequencing identified 130 enriched miRNAs in GC-exo. Among the enriched miRNAs, miR-92a-3p plays a major role in activating ERK signaling via inhibition of PTEN expression. In addition, inhibiting ERK signaling with PD98059 significantly reduced the expression of PD-L1 in macrophages and, therefore, reversed the immunosuppressive PMN and inhibited the colonization of GC cells in the lungs. This study identified a novel mechanism of GC-exo mediated PD-L1 expression in lung macrophages that facilitates lung PMN formation and GC pulmonary metastasis, which also provided a potential therapeutic target for GC with pulmonary metastasis treatment.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
·
癌症生物学
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
·
2019
·
IF 8.063
Kerong Chen,Xiaoqing Cao,Min Li,Yujie Su,Huipeng Li,Mengying Xie,Ziqi Zhang,Hongbin Gao,Xiangting Xu,Yi Han,Jianping Zhou,Wei Wang
Genetically engineered mesenchymal stem cells (MSCs), as non-viral gene delivery platforms, are rapidly evolving in tumor therapy due to their low immunogenicity and natural tumor-homing capacity. Methods: In this paper, we selected reconstituted high-density lipoprotein (rHDL), a lipoprotein-bioinspired nanovector with specific binding ability to scavenger receptor B type I (SR-BI) expressed on MSCs, as a transfection agent to genetically modify MSCs. pDNA encoding tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was used as a functional gene to be transfected into the nucleus of MSCs for TRAIL expression. Lauric acid-coupled polyethyleneimine (PEI-LA) as an amphiphilic cationic polymer was synthesized to electrostatically bind to pDNA, and then incorporated into rHDL to form rHDL/PEI-LA/pDNA nanoparticles. Results: The nanoparticles exhibited homogenous particle size and excellent serum stability in vitro . Meanwhile, this SR-BI-targeted rHDL performed efficient intracellular gene delivery, specific lysosome-independent mechanism of cellular uptake and high transfection of pDNA towards MSCs. Moreover, high TRAIL expression in MSCs was detected after rHDL-mediated transfection. In vitro and in vivo results indicated that genetically engineered MSCs could accurately target to B16F10 cells, thereby producing significant apoptosis-inducing effect on aggressive melanoma. Conclusion: TRAIL-expressing MSCs engineered by rHDL nanovector was an efficient and hypotoxic method for stem cells-based pulmonary melanoma metastasis-targeting therapy.
研究领域:
癌症生物学
·
基因治疗
·
纳米技术
·
干细胞研究
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）