Tumor-Associated Neutrophil Extracellular Traps Regulating Nanocarrier-Enhanced Inhibition of Malignant Tumor Growth and Distant Metastasis.
Tumor-Associated Neutrophil Extracellular Traps Regulating Nanocarrier-Enhanced Inhibition of Malignant Tumor Growth and Distant Metastasis.
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DOI：
10.1021/acsami.1c18660
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发表时间：
2021-12
影响因子：
9.5
通讯作者：
Haoyuan Yin;Hongdan Lu;Yaokun Xiong;Lu Ye;C. Teng;Xiang Cao;Shengnan Li;S. Sun;Wentao Liu-Wenta
中科院分区：
文献类型：
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作者：
Haoyuan Yin;Hongdan Lu;Yaokun Xiong;Lu Ye;C. Teng;Xiang Cao;Shengnan Li;S. Sun;Wentao Liu-Wenta
Tumor-associated neutrophil extracellular traps (NETs) play a critical role in promoting tumor growth and assisting tumor metastasis. Herein, a smart nanocarrier (designated as mP-NPs-DNase/PTX) based on regulating tumor-associated NETs has been developed, which consists of a paclitaxel (PTX) prodrug nanoparticle core and a poly-l-lysine (PLL) conjugated with the matrix metalloproteinase 9 (MMP-9)-cleavable Tat-peptide-coupled deoxyribonuclease I (DNase I) shell. After accumulating at the site of the tumor tissue, the nanocarrier can release DNase I in response to MMP-9 to degrade the structure of NETs. Then, the remaining moiety can uptake the tumor cells via the mediation of exposed cell penetrating peptide, and the PTX prodrug nanoparticles will lyse in response to the high intracellular concentration of reduced glutathione to release PTX to exert a cytotoxic effect of tumor cells. Through in vitro and in vivo evaluations, it has been proven that mP-NPs-DNase/PTX could serve as potential NET-regulated nanocarrier for enhanced inhibition of malignant tumor growth and distant metastasis.
