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Macrophage membrane-biomimetic adhesive polycaprolactone nanocamptothecin for improving cancer-targeting efficiency and impairing metastasis

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Bioactive Materials 2023年第2期20卷 449-462页

作者： Kangkang Ying Yifeng Zhu Jianqin Wan Chenyue Zhan Yuchen Wang Binbin Xie Peirong Xu Hongming Pan Hangxiang Wang The First Affiliated Hospital NHC Key Laboratory of Combined Multi-Organ TransplantationZhejiang University School of MedicineHangzhouZhejiang Province310003PR China Jinan Microecological Biomedicine Shandong Laboratory JinanShandong Province250117PR China Department of Hepatobiliary Surgery The First Affiliated HospitalWenzhou Medical UniversityWenzhouZhejiang Province325000PR China Department of Medical Oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouZhejiang Province310016PR China Department of Chemical Engineering Zhejiang UniversityHangzhouZhejiang Province310027PR China

The recent remarkable success and safety of mRNA lipid nanoparticle technology for producing severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines has stimulated intensive efforts to expand nanoparticle strategies to treat various *** synthetic nanoparticles have been developed for pharmaceutical delivery and cancer ***,only a limited number of nanotherapies have enter clinical trials or are clinically *** administered nanotherapies are likely to be sequestered by host mononuclear phagocyte system(MPS),resulting in suboptimal pharmacokinetics and insufficient drug concentrations in *** drug-delivery formulations have emerged as an alternative approach to evade the MPS and show potential to improve drug therapeutic *** we developed a biodegradable polymer-conjugated camptothecin prodrug encapsulated in the plasma membrane of lipopolysaccharide-stimulated *** conjugation revived the parent camptothecin agent(e.g.,7-ethyl-10-hydroxy-camptothecin),enabling lipid nanoparticle ***,macrophage membrane cloaking transformed the nonadhesive lipid nanoparticles into bioadhesive nanocamptothecin,increasing the cellular uptake and tumor-tropic effects of this biomimetic *** tested in a preclinical murine model of breast cancer,macrophage-camouflaged nanocamptothecin exhibited a higher level of tumor accumulation than uncoated ***,intravenous administration of the therapy effectively suppressed tumor growth and the metastatic burden without causing systematic *** study describes a combinatorial strategy that uses polymeric prodrug design and cell membrane cloaking to achieve therapeutics with high efficacy and low *** approach might also be generally applicable to formulate other therapeutic candidates that are not compatible or miscible with biomimetic delivery carriers.

关键词： Polymer prodrug Macrophage membrane Cancer nanomedicine antimetastasis Nanocamptothecin

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Extracts of Celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating Epithelial-Mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells

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Chinese Journal of Integrative Medicine 2019年第5期25卷 334-341页

作者： QIAN Ya-yun SHI You-yang LU Song-hua YANG Ting ZHAO Xue-yu YAN Yan LI Wen-yuan LIU Yan-qing Institute of Traditional Chinese Medicine and Western Medicine School of MedicineYangzhou UniversityJiangsu Province(225009)China Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases YangzhouJiangsu Province(225001)China Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Jiangsu Province(225009)China

Objective: To evaluate the effects of Celastrus Orbiculatus extracts(COE) on metastasis in hypoxiainduced hepatocellular carcinoma cells(Hep G2) and to explore the underlying molecular mechanisms. Methods:The effect of COE(160, 200 and 240 μg/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide(MTT), scratch-wound and transwell assays, respectively. Co Cl2 was used to establish a hypoxia model in vitro. Effects of COE on the expressions of E-cadherin, vimentin and N-cadherin were investigated with Western blot and immuno?uorescence analysis,respectively. Results: COE inhibited proliferation and metastasis of hypoxia-induced hepatocellular carcinoma cells in a dose-dependent manner(P<0.01). Furthermore, the expression of epithelial-mesenchymal transition(EMT) related markers were also remarkably suppressed in a dose-dependent manner(P<0.01). In addition, the upstream signaling pathways, including the hypoxia-inducible factor 1α(Hif-1α) and Twist1 were suppressed by COE. Additionally, the Hif-1α inhibitor 3-5'-hydroxymethyl-2'-furyl)-1-benzylindazole(YC-1), potently suppressed cell invasion and migration as well as expression of EMT in hypoxia-induced Hep G2 cells. Similarly, the combined treatment with COE and YC-1 showed a synergistic effect(P<0.01) compared with the treatment with COE or YC-1 alone in hypoxia-induced Hep G2 cells. Conclusions: COE signi?cantly inhibited the tumor metastasis and EMT by suppressing Hif-1α/Twist1 signaling pathway in hypoxia-induced Hep G2 cell. Thus, COE might have potential effect to inhibit the progression of Hep G2 in the context of tumor hypoxia.

关键词： Celastrus Orbiculatus hepatocellular carcinoma antimetastasis epithelial-mesenchymal transition Hif-1α/Twist1 signaling pathway

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Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence

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World Journal of Gastroenterology 2014年第32期20卷 11384-11393页

作者： Chun-Jen Liu Juliana Chang Po-Huang Lee Deng-Yn Lin Cheng-Chung Wu Long-Bin Jeng Yih-Jyh Lin King-Tong Mok Wei-Chen Lee Hong-Zen Yeh Ming-Chih Ho Sheng-Shun Yang Mei-Due Yang Ming-Chin Yu Rey-Heng Hu Cheng-Yuan Peng Kuan-Lang Lai Stanley Shi-Chung Chang Pei-Jer Chen Graduate Institute of Clinical Medicine Hepatitis Research Center and Department of Internal Medicine National Taiwan University College of Medicine and National Taiwan University Hospital Chang Gung Memorial Hospital-Linkou Medical Center and Chang Gung University Taichung Veterans General Hospital China Medical University Hospital National Cheng Kung University Hospital Kaohsiung Veterans General Hospital Medigen Biotechnology Corporation

AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection.

关键词： Antiangiogenesis antimetastasis Adjuvant therapy Disease-free survival Heparanase inhibitor Hepatocellular carcinoma PI-88 Tumor recurrence

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Small molecules regulate homeostasis of cytokines for suppression of pulmonary fibrosis and tumor metastasis

Small molecules regulate homeostasis of cytokines for suppre...

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第二届全国“跨学科蛋白质研究”学术讨论会

作者：梁伟 Protein & Peptide Pharmaceutical Laboratory Institute of BiophysicsChinese Academy of Sciences

Increasing evidence points to involvement of the fibrotic microenvironment in cancer initiation and progression. Here we demonstrate that mice with lung fibrosis challenged with tumors show an increased incidence of lung metastasis and shorter life spans.A fibrotic environment in the lung results in increased abundance of TGF-β1 and CD4+CD25+FoxP3+regulatory T cells and a decreased proportion of activated effector T *** grave immunosuppressive environment favors tumor localization and growth. Naringenin significantly reduces lung metastases in mice with pulmonary fibrosis and increases their survival by improving the immunosuppressive environment through downregulating TGF-β1 and reducing levels of regulatory T *** together,these data indicate that naringenin could be an ideal therapeutic agent in the treatment of both cancer and fibrosis.

关键词： Pulmonary fibrosis Lung metastasis Naringenin TGF-β1 Antifibrosis antimetastasis Treg.

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