期刊
BIOACTIVE MATERIALS
卷 9, 期 -, 页码 120-133出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.07.021
关键词
Self-assembly; Organelle-mimicking; Nuclear delivery; Dynamic cascade process; Cancer therapy
资金
- National Science Fund for Distinguished Young Scholars [31825012]
- National Natural Science Foundation of China [21875116, 31961143004, 81921004, 31900952, 51973090]
- Tianjin Science Fund for Distinguished Young Scholars [17JCJQJC44900]
- Guangdong Basic and Applied Basic Research Foundation [2018A030313446, 2019A1515011706, 2019A1515110638]
- China Postdoctoral Science Foundation [BX20190149, 2019M662972]
Organelles are responsible for the storage and transport of substances in living systems. Researchers have developed a biomimetic delivery strategy inspired by natural cargo delivery by organelles, which can improve the efficiency of cancer therapy.
Organelles are responsible for the efficient storage and transport of substances in living systems. A myriad of extracellular vesicles (EVs) acts as a bridge to exchange signaling molecules in cell-cell communication, and the highly dynamic tubulins and actins contribute to efficient intracellular substance transport. The inexhaustible cues of natural cargo delivery by organelles inspire researchers to explore the construction of biomimetic architectures for smart delivery carriers. Herein, we report a 10-hydroxycamptothecin (HCPT)-peptide conjugate HpYss that simulates the artificial EV-to-filament transformation process for precise liver cancer therapy. Under the sequential stimulus of extracellular alkaline phosphatase (ALP) and intracellular glutathione (GSH), HpYss proceeds via tandem self-assembly with a morphological transformation from nanoparticles to nanofibers. The experimental phase diagram elucidates the influence of ALP and GSH contents on the self-assembled nanostructures. In addition, the dynamic transformation of organelle-mimetic architectures that are formed by HpYss in HepG2 cells enables the efficient delivery of the anticancer drug HCPT to the nucleus, and the size-shape change from extracellular nanoparticles (50-100 nm) to intracellular nanofibers (4-9 nm) is verified to be of key importance for nuclear delivery. Nuclear targeting of HpYss amplifies apoptosis, thus significantly enhancing the inhibitory effect of HCPT (>10-fold) to HepG2 cells. Benefitting from the spatiotemporally controlled nanostructures, HpYss exhibited deep penetration, enhanced accumulation, and long-term retention in multicellular spheroid and xenograft models, potently abolishing liver tumor growth and preventing lung metastasis. We envision that our organelle-mimicking delivery strategy provides a novel paradigm for designing nanomedicine to cancer therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据