BBB-penetrating codelivery liposomes treat brain metastasis of non-small cell lung cancer with EGFR(T790M) mutation
文献类型：期刊论文
| 作者 | Yin, Weimin1,2; Zhao, Yuge1,3; Kang, Xuejia1; Zhao, Pengfei1; Zhao, Xuhong1; Mo, Xiaopeng1; Wang, Yakun1; Huang, Yongzhuo1,4
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| 刊名 | THERANOSTICS
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| 出版日期 | 2020 |
| 卷号 | 10期号:14页码:6122-6135 |
| 关键词 | brain targeting delivery tumor-associated macrophage non-small cell lung cancer (NSCLC) drug resistance tyrosine kinase inhibitors (TKI) EGFR T790M mutation |
| ISSN号 | 1838-7640 |
| DOI | 10.7150/thno.42234 |
| 通讯作者 | Huang, Yongzhuo(yzhuang@simm.ac.cn) |
| 英文摘要 | EGFR TKI therapy has become a first-line regimen for non-small cell lung cancer (NSCLC) patients with EGRF mutations. However, there are two big challenges against effective therapy-the secondary EGFR mutation-associated TKI resistance and brain metastasis (BMs) of lung cancer. The BMs is a major cause of death for advanced NSCLC patients, and the treatment of BMs with TKI resistance remains difficult. Methods: Tumor-associated macrophages (TAM) is a promising drug target for inhibiting tumor growth, overcoming drug resistance, and anti-metastasis. TAM also plays an essential role in regulating tumor microenvironment. We developed a dual-targeting liposomal system with modification of anti-PD-L1 nanobody and transferrin receptor (TfR)-binding peptide T12 for codelivery of simvastatin/gefitinib to treat BMs of NSCLC. Results: The dual-targeting liposomes could efficiently penetrate the blood-brain barrier (BBB) and enter the BMs, acting on TAM repolarization and reversal of EGFR(T790M)-associated drug resistance. The treatment mechanisms were related to the elevating ROS and the suppression of the EGFR/Akt/Erk signaling pathway. Conclusion: The dual-targeting liposomal codelivery system offers a promising strategy for treating the advanced EGFR(T790M) NSCLC patients with BMs. |
| WOS关键词 | TUMOR-MICROENVIRONMENT ; RESISTANCE ; MACROPHAGES ; MECHANISMS ; DELIVERY ; DISEASE |
| 资助项目 | NFSC[81925035] ; NFSC[81673382] ; NFSC[81521005] ; Strategic Priority Research Program of CAS[XDA12050307] ; National Special Project for Significant New Drugs Development[2018ZX09711002-010-002] ; CAS Scientific Research and Equipment Development Project[YZ201437] ; Fudan-SIMM Joint Research Fund[FU-SIMM20174009] |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000534615100004 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/280088]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Huang, Yongzhuo |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Fudan Univ, Childrens Hosp & Biomed Sci, Inst Pediat, Shanghai 200032, Peoples R China 3.Nanchang Univ, Coll Pharm, 461 Bayi Rd, Nanchang 330006, Jiangxi, Peoples R China 4.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipi, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yin, Weimin,Zhao, Yuge,Kang, Xuejia,et al. BBB-penetrating codelivery liposomes treat brain metastasis of non-small cell lung cancer with EGFR(T790M) mutation[J]. THERANOSTICS,2020,10(14):6122-6135. |
| APA | Yin, Weimin.,Zhao, Yuge.,Kang, Xuejia.,Zhao, Pengfei.,Zhao, Xuhong.,...&Huang, Yongzhuo.(2020).BBB-penetrating codelivery liposomes treat brain metastasis of non-small cell lung cancer with EGFR(T790M) mutation.THERANOSTICS,10(14),6122-6135. |
| MLA | Yin, Weimin,et al."BBB-penetrating codelivery liposomes treat brain metastasis of non-small cell lung cancer with EGFR(T790M) mutation".THERANOSTICS 10.14(2020):6122-6135. |
入库方式： OAI收割
来源：上海药物研究所
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