Stepwise targeting and responsive lipid-coated nanoparticles for enhanced tumor cell sensitivity and hepatocellular carcinoma therapy
文献类型：期刊论文
| 作者 | Li, Ying2; Miao, Yunqiu1,3; Chen, Mingshu1,3; Chen, Xi1; Li, Feifei1; Zhang, Xinxin1 ; Gan, Yong1
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| 刊名 | THERANOSTICS
 |
| 出版日期 | 2020 |
| 卷号 | 10期号:8页码:3722-3736 |
| 关键词 | drug delivery pH sensitive charge conversion tumor targeting hepatocellular carcinoma |
| ISSN号 | 1838-7640 |
| DOI | 10.7150/thno.42008 |
| 通讯作者 | Zhang, Xinxin(xinxinzhang@simm.ac.cn) |
| 英文摘要 | Rationale: Antitumor drug delivery faces multiple barriers that require consecutively achieving tumor targeting, selective cellular uptake and sufficient intracellular drug dosage. Methods: Herein, we designed smart nanoparticles (GPDC-MSNs) that can accumulate stepwise in tumor tissues, selectively enter cancer cells by responding to the acidic tumor extracellular environment, and achieve considerable drug release in the intracellular microenvironment. The GPDC-MSNs comprise the synthesized material galactosyl-conjugated PEO-PPO-PEO (Gal-P123) for hepatocellular carcinoma (HCC) targeting, the tumor extracellular pH-responsive lipid (2E)-4-(dioleostearin)-amino-4-carbonyl-2-butenonic (DC) for selective cellular internalization, and antitumor drug irinotecan (CPT-11)-loaded mesoporous silica nanoparticles (MSNs) for on-demand intracellular drug release. Results: GPDC-MSNs are negatively charged at pH 7.4 and promote active HCC targeting mediated by the asialoglycoprotein receptor. Upon reaching the weakly acidic tumor microenvironment, the nanoparticles undergo charge conversion to neutral, enhancing cellular internalization. Moreover, the encapsulated CPT-11 can be retained within GPDC-MSNs in the blood circulation but undergo intracellular burst release, which facilitates the apoptosis of tumor cells. GPDC-MSNs significantly increased HCC selectivity in vivo and exhibited up to 25 times higher accumulation in tumor tissue than in normal hepatic tissue, thus achieving superior antitumor efficacy and low systemic toxicity. Conclusion: This stepwise-responsive nanoparticle should serve as a valuable platform and promising strategy for HCC treatment. |
| WOS关键词 | MESOPOROUS SILICA NANOPARTICLES ; DRUG-DELIVERY ; INTERSTITIAL PH ; GENE DELIVERY ; CHEMOTHERAPY ; RESISTANCE ; RELEASE ; SYSTEM |
| 资助项目 | National Natural Science Foundation of China[81973250] ; National Natural Science Foundation of China[81571796] ; National Science and Technology Major Project[2018ZX09721002 -003] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDA120 50307] |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000518768400023 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/281148]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhang, Xinxin |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China 2.Shenzhen Univ, Sch Med, Dept Pharm, Shenzhen 518060, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Ying,Miao, Yunqiu,Chen, Mingshu,et al. Stepwise targeting and responsive lipid-coated nanoparticles for enhanced tumor cell sensitivity and hepatocellular carcinoma therapy[J]. THERANOSTICS,2020,10(8):3722-3736. |
| APA | Li, Ying.,Miao, Yunqiu.,Chen, Mingshu.,Chen, Xi.,Li, Feifei.,...&Gan, Yong.(2020).Stepwise targeting and responsive lipid-coated nanoparticles for enhanced tumor cell sensitivity and hepatocellular carcinoma therapy.THERANOSTICS,10(8),3722-3736. |
| MLA | Li, Ying,et al."Stepwise targeting and responsive lipid-coated nanoparticles for enhanced tumor cell sensitivity and hepatocellular carcinoma therapy".THERANOSTICS 10.8(2020):3722-3736. |
入库方式： OAI收割
来源：上海药物研究所
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