Nanodiamonds Mediate Oral Delivery of Proteins for Stem Cell Activation and Intestinal Remodeling in Drosophila
Nanodiamonds Mediate Oral Delivery of Proteins for Stem Cell Activation and Intestinal Remodeling in Drosophila
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纳米金刚石介导果蝇干细胞激活和肠道重塑的蛋白质口服递送
DOI：
10.1021/acsami.7b04788
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发表时间：
2017
影响因子：
9.5
通讯作者：
Song Haiyun
中科院分区：
文献类型：
--
作者：
Hu Xingjie;Li Xiaojiao;Yin Min;Li Ping;Huang Ping;Wang Lihua;Jiang Yiguo;Wang Hui;Chen Nan;Fan Chunhai;Song Haiyun
将外源性生物大分子引入生命系统是基因组编辑、癌症免疫治疗和干细胞重编程等领域的重要研究方向。虽然目前的策略通常依赖于核酸转染，但功能蛋白的直接递送具有增强的特异性，增加的安全性，以及快速和时间调节是非常可取的。然而，完整和生物活性蛋白的细胞内递送，特别是在体内，仍然很少被探索。在这项研究中，我们开发了一种基于纳米金刚石（NDs）的蛋白质递送系统，该系统在培养细胞和果蝇体内具有高吸附、高效率和有效的全功能蛋白质的胞质释放。通过活细胞成像，我们观察到一种新的现象，即大量内化的nds -蛋白复合物拒绝与早期内核体融合，从而逃避了溶酶体中的蛋白质降解。更重要的是，我们证明了膳食NDs-RNase诱导肠细胞凋亡，刺激肠干细胞再生分裂，增加果蝇肠道干细胞和前体细胞的数量。由于干细胞在体内不易被外源性药物获取，nds介导的蛋白质口服递送为调节肠道重塑的干细胞微环境提供了一种新的途径，这对结直肠癌治疗和再生医学具有重要意义。
Introduction of exogenous biomacromolecules into living systems is of great interest in genome editing, cancer immunotherapy, and stem cell reprogramming. Whereas current strategies generally depend on nucleic acids transfection, direct delivery of functional proteins that provides enhanced specificity, increased safety, and fast and temporal regulation is highly desirable. Nevertheless, intracellular delivery of intact and bioactive proteins, especially in vivo, remains poorly explored. In this study, we developed a nanodiamonds (NDs)-based protein delivery system in cultured cells and inDrosophilathat showed high adsorption, high efficiency, and effective cytosolic release of fully functional proteins. Through live-cell imaging, we observed a novel phenomenon wherein a substantial amount of internalized NDs–protein complex rejected fusion with the early endosome, thereby evading protein degradation in the lysosome. More significantly, we demonstrated that dietary NDs–RNase induced apoptosis in enterocytes, stimulating regenerative divisions in intestinal stem cells and increasing the number of stem cells and precursor cells inDrosophilaintestine. As stem cells are poorly accessible by exogenous agents in vivo, NDs-mediated oral delivery of proteins provides a new approach to modulate the stem cell microenvironment for intestinal remodeling, which has important implications for colorectal cancer therapy and regenerative medicine.