CANCER CHEMOTHERAPY AND PHARMACOLOGY
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2024
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IF 2.7
Ma Xuan,Sun Zhenou,Chen Hui,Cao Lixing,Zhao Shuang,Fan Lihong,Zhao Chong,Yin Shutao,Hu Hongbo
Purpose 18β-glycyrrhetinic acid (GA), the main metabolite of glycyrrhizic acid extracted from the root of licorice, has been reported to possess anti-cancer and immunomodulatory activity, but the mechanisms are not well understood. Recent studies have shown that ferroptosis of immune cells is involved in tumor-associated immune suppression. The purpose of this study was to investigate whether the enhanced immune response via inhibiting immune cell ferroptosis contributed to the anticancer effect of 18β-GA. Methods Lewis Lung carcinoma mouse model and Murine CD8 + T cell culture model were used to examine the changes of immune response and ferroptosis of immune cells. Results We found that 18β-GA was effective against lung cancer accompanied by enhanced activation of tumor-infiltrating CD8 + T cells in Lewis Lung carcinoma mouse model. Furthermore, we demonstrated that the boosted immune response by GA was attributed to its ability to inhibit arachidonic acid (AA)-mediated CD8 + T ferroptosis via suppressing CD36 expression. Conclusion The findings of the present study unraveled a novel mechanism underlying the anti-cancer and immunomodulatory activity of 18β-GA and support that 18β-GA holds potential to be used as an immune enhancer for lung cancer prevention or treatment.
研究领域:
肿瘤学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2018
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IF 8.097
Juanjuan Li,Xuan Meng,Jian Deng,Di Lu,Xin Zhang,Yanrui Chen,Jundong Zhu,Aiping Fan,Dan Ding,Deling Kong,Zheng Wang,Yanjun Zhao
Nanoparticulate antitumor photodynamic therapy (PDT) has been suffering from the limited dose accumulation in tumor. Herein, we report dually hypoxia- and singlet oxygen-responsive polymeric micelles to efficiently utilize the photosensitizer deposited in the disease site and hence facilely improve PDT’s antitumor efficacy. Tailored methoxy poly(ethylene glycol)-azobenzene-poly(aspartic acid) copolymer conjugate with imidazole as the side chains was synthesized. The conjugate micelles (189 ± 19 nm) obtained by self-assembly could efficiently load a model photosensitizer, chlorin e6 (Ce6) with a loading of 4.1 ± 0.5% (w/w). The facilitated cellular uptake of micelles was achieved by the triggered azobenzene collapse that provoked poly(ethylene glycol) shedding; rapid Ce6 release was enabled by imidazole oxidation that induced micelle disassembly. In addition, the singlet oxygen-mediated cargo release not only addressed the limited diffusion range and short half-life of singlet oxygen but also decreased the oxygen level, which could in turn enhance internalization and increase the intracellular Ce6 concentration. The hypoxia-induced dePEGylation and singlet oxygen-triggered Ce6 release was demonstrated both in aqueous buffer and in Lewis lung carcinoma (LLC) cells. The cellular uptake study demonstrated that the dually responsive micelles could deliver significantly more Ce6 to the cells, which resulted in a substantially improved cytotoxicity. This concurred well with the superior in vivo antitumor ability of micelles in a LLC tumor-bearing mouse model. This study presented an intriguing nanoplatform to realize interactively triggered photosensitizer delivery and improved antitumor PDT efficacy.
研究领域:
药学
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生物医学工程
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肿瘤学
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材料科学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
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2017
·Vol. 22
·期 2
·325
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IF 2.861
Hong Yao,Bing Chen,Yanyan Zhang,Huigen Ou,Yuxiang Li,Shaoguang Li,Peiying Shi,Xinhua Lin
Selaginella doederleiniiHieron has been traditionally used as a folk antitumor herbal medicine in China. In this paper, the phytochemical components of the total biflavonoids extract fromS. doederleiniiwere studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. Four types of biflavonoids fromS. doederleinii, including IC3′–IIC8′′, IC3′–IIC6′′, IC3′–IIC3′′′, and C–O linked biflavonoids were examined originally using QTOF MS/MS. The fragmentation behavior of IC3′–IIC3′′′ linked biflavonoids was reported for the first time. A total of twenty biflavonoids were identified or tentatively characterized and eight biflavonoids were found fromS. doederleiniifor the first time. Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts fromS. doederleinii. The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant.Keywords:Selaginella doederleinii;HPLC-ESI-QTOF MS/MS;biflavonoids;murine B16 melanoma cell;mouse lewis lung cancer (LLC) cell;LLC mouse model
研究领域:
药用植物学
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药物化学
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肿瘤学
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分析化学
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产品关联
DOI
PubMed
高影响因子
BULLETIN DU CANCER
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2023
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IF 1.2
Siyan Zhang,Xingyao Zhang,Dong Zhang,Liang Wei,Bin Xiong,Qi Meng,Shougang Jiang
Summary Introduction Gambogic acid (GA) as an active compound isolated from Gamboge, have been investigated for many years and proved to be a promising natural anticancer agent for clinical treatment . This study aimed to investigate the inhibitory effect of docetaxel (DTX) combined with gambogic acid on bone metastasis of lung cancer. Methods The anti-proliferation effect of the combination of DTX and GA on Lewis lung cancer (LLC) cells was determined by MTT assays . The anticancer effect of the combination of DTX and GA on bone metastasis of lung cancer in vivo was explored. Evaluation of the efficacy of drug therapy was performed by comparing the degree of bone destruction and the pathological section of bone tissue of the treated mice with that of the control mice. Results In vitro cytotoxicity, cell migration, and osteoclast-induced formation assay showed that GA enhanced the therapeutic effect of DTX in Lewis lung cancer cell with a synergistic effect. In an orthotopic mouse model of bone metastasis, the average survival of the DTX + GA combination group (32.61d ± 1.06 d) was significantly increased compared with that of the DTX group (25.75 d ± 0.67 d) or GA group (23.99 d ± 0.58 d), * P < 0.01. Conclusion The combination of DTX and GA has synergistic effect and resulted in more effective inhibition of tumor metastasis , providing a strong preclinical rationale for the clinical development of the DTX + GA combination for treating bone metastasis of lung cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2022
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IF 11.467
Siqi Ma,Zhaoqing Cong,Jiaxing Wei,Weiya Chen,Di Ge,Feifei Yang,Yonghong Liao
Very little is currently known about how inhaled nanomedicine for lung cancer treatment overcomes biological barriers hampering the tumor availability of drug and nanoparticles . Here, we developed a size-transformable nanocarrier (~ 119 nm) in which small-size nanoparticles (~ 28 nm) were loaded in the large nanocarrier after the addition of modified hyaluronan and could be released upon size-transformation at tumor tissue. Subsequently, the pulmonary and tumor pharmacokinetics of the two nanocarriers containing 7-ethyl-10-hydroxycamptothecin (SN38) and a covalently linked fluorescent sonosensitizer were comparatively investigated after intratracheal instillation to mice bearing orthotopic Lewis lung carcinoma tumors. The results showed that both instilled nanoparticles seemed to transport drug to tumor by direct access and transcytosis of nanoparticles, and diffusion of the released drug with the latter accounting for a great proportion of the drug tumor bioavailability. Relative to the small-size nanocarrier, the size-transformable counterpart appeared to restrict the mucociliary and absorption clearances from the lung and the clearance from the tumor interstitium to circulation, leading to increases in lung and tumor bioavailability of SN38 by 58.5% and 199%, respectively. In addition, the size-transformable nanoformulation conferred deep tumor penetration and sustained levels of both sonosensitizer and SN38 within tumors and simultaneously exerted sonodynamic- and chemo-therapies. Overall, the pulmonary delivery of size-transformable nanocarrier could co-deliver sonosensitizer and drug to deep tumor sites with enhanced tumor accumulation to realize combination therapy in lung cancer.
研究领域:
纳米医学
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癌症治疗
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药理学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Xing Zhao,Haifei Guo,Hriday Bera,Huiyang Jiang,Yang Chen,Xiong Guo,Xidong Tian,Dongmei Cun,Mingshi Yang
Paclitaxel (PTX) remains a cornerstone in the treatment of locally advanced and metastatic lung cancer. To improve its therapeutic indices against lung cancer, novel redox-sensitive pullulan/PTX-based prodrug NPs (PULL–SS–PTX NPs) were accomplished, which were further surface-decorated with transferrin (TF), a cancer cell-targeting ligand, to afford TF–PULL–SS–PTX NPs. These prodrug NPs (drug content, >37% and average size, 134–163 nm) rapidly dismantled their self-assembled architecture upon exposure to simulated reducing conditions, causing a triggered drug release as compared to the control scaffold (PULL–CC–PTX NPs). These scaffolds also evidenced outstanding colloidal stability, cellular uptake efficiency, and discriminating cytotoxicity between the cancer and healthy cells. Intravenously delivered redox-sensitive NPs exhibited improved tumor-suppressing properties as compared to the control nanovesicles (PULL–CC–PTX NPs) in a B16–F10 melanoma lung metastasis mice model. The targeting efficiency and associated augmented anticancer potentials of TF–PULL–SS–PTX NPs relative to TF-free redox-responsive NPs and Taxol intravenous injection were also established on the transferrin receptor (TFR) overexpressed Lewis lung carcinoma (LLC–luc) cell-bearing mice model. Moreover, the TF-functionalized scaffold displayed a reduced systemic toxicity compared to that of Taxol intravenous injection. Overall, the proposed TF-decorated prodrug NPs could be a promising nanomedicine for intracellular PTX delivery against metastatic lung cancer.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
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IF 5.8
Liqun Jiang,Ziyao Wang,Yan Wang,Shuo Liu,Ya Xu,Cong Zhang,Lei Li,Sujia Si,Bingmei Yao,Wenjin Dai,Huiyang Li
The re-education of tumor-associated macrophages (TAMs) is an effective strategy to inhibit the growth and metastasis of lung cancer. We have reported that chitosan could re-educate the TAMs and then inhibit cancer metastasis; however, the re-exposure of chitosan from the chemical corona on their surface is critical for this effect. In this study, a strategy was proposed to re-expose the chitosan from chemical corona, and a sustained H 2 S generation was applied to enhance the immunotherapy of chitosan. To achieve this objective, an inhalable microsphere (namely F/Fm) was designed, which could be degraded by the matrix metalloproteinase in lung cancer, releasing two kinds of nanoparticles ; in an external magnetic field, these nanoparticles can aggregate with each other, and β-cyclodextrin on the surface of one nanoparticle can be hydrolyzed by amylase on the surface of another nanoparticle, leading to the re-exposure of chitosan in the inner layer of β-cyclodextrin and the release of diallyl trisulfide for H 2 S generation. In vitro , the expression of CD86 and secretion of TNF-α by TAMs was increased by F/Fm, proving the re-education of TAMs, and the apoptosis of A549 cells was promoted with the migration and invasion being inhibited. In the Lewis lung carcinoma-bearing mouse, the F/Fm re-educated the TAMs and provided a sustained generation of H 2 S in the region of lung cancer, effectively inhibiting the growth and metastasis of lung cancer cells. This work provides a new strategy for the treatment of lung cancer in combination of re-education of TAMs by chitosan and the adjuvant chemotherapy by H 2 S.
研究领域:
癌症生物学
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药学
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纳米技术
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免疫学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2022
·
IF 10.383
Xianglong Yu,Ning Han,Ziyi Dong,Yunni Dang,Qing Zhang,Wenjun Hu,Changhai Wang,Shouying Du,Yang Lu
Tumor metastasis and recurrence are recognized to be the main causes of failure in cancer treatment. To address these issues, an “all in one” and “one for all” nanoplatform was established for combined “chemo–immuno–photothermal” therapy with the expectation to improve the antitumor efficacy. Herein, Docetaxel (DTX, a chemo-agent) and cynomorium songaricum polysaccharide (CSP, an immunomodulator) were loaded into zein nanoparticles coated by a green tea polyphenols/iron coordination complex (GTP/FeIII, a photothermal agent). From the result, the obtained nanoplatform denoted as DTX-loaded Zein/CSP-GTP/FeIII NPs was spherical in morphology with an average particle size of 274 nm, and achieved pH-responsive drug release. Moreover, the nanoplatform exhibited excellent photothermal effect both in vitro and in vivo. It was also observed that the nanoparticles could be effectively up take by tumor cells and inhibited their migration. From the results of the in vivo experiment, this nanoplatform could completely eliminate the primary tumors, prevent tumor relapses on LLC (Lewis lung cancer) tumor models, and significantly inhibit metastasis on 4T1 (murine breast cancer) tumor models. The underlying mechanism was also explored. It was discovered that this nanoplatform could induce a strong ICD effect and promote the release of damage-associated molecular patterns (DAMPs) including CRT, ATP, and HMGB1 by the dying tumor cells. And the CSP could assist the DAMPs in inducing the maturation of dendritic cells (DCs) and facilitate the intratumoral infiltration of T lymphocytes to clear up the residual or disseminated tumor cells. In summary, this study demonstrated that the DTX-loaded Zein/CSP-GTP/FeIII is a promising nanoplatform to completely inhibit tumor metastasis and recurrence.
研究领域:
纳米技术
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癌症研究
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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