Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
State Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
Int J Nanomedicine. 2021 Feb 26;16:1575-1586. doi: 10.2147/IJN.S293067. eCollection 2021.
Exosomes are a type of membrane vesicles secreted by living cells. Recent studies suggest exosome-like nanovesicles (ELNVs) from fruits and vegetables are involved in tissue renewal process and functional regulation against inflammatory diseases or cancers. However, there are few reports on ELNVs derived from medicinal plants.
ELNVs derived from (Lour.) Merr. (ACNVs) were isolated and characterized. Cytotoxicity, antiproliferative and apoptosis-inducing capacity of ACNVs against hepatoma carcinoma cell were assessed. The endocytosis mechanism of ACNVs was evaluated on Hep G2 cells in the presence of different endocytosis inhibitors. In vivo distribution of ACNVs was detected in healthy and tumor-bearing mice after scavenger receptors (SRs) blockade. PEG engineering of ACNVs was achieved through optimizing the pharmacokinetic profiles. In vivo antitumor activity and toxicity were evaluated in Hep G2 cell xenograft model.
ACNVs were isolated and purified using a differential centrifugation method accompanied by sucrose gradient ultracentrifugation. The optimized ACNVs had an average size of about 119 nm and showed a typical cup-shaped nanostructure containing lipids, proteins, and RNAs. ACNVs were found to possess specific antitumor cell proliferation activity associated with an apoptosis-inducing pathway. ACNVs could be internalized into tumor cells mainly via phagocytosis, but they were quickly cleared once entering the blood. Blocking the SRs or PEGylation decoration prolonged the blood circulation time and increased the accumulation of ACNVs in tumor sites. In vivo antitumor results showed that PEGylated ACNVs could significantly inhibit tumor growth without side effects.
This study provides a promising functional nano platform derived from edible that can be used in antitumor therapy with negligible side effects.
外泌体是活细胞分泌的一种膜囊泡。最近的研究表明，来自水果和蔬菜的外泌体样纳米囊泡（ELNVs）参与组织更新过程，并对炎症性疾病或癌症的功能调节具有重要作用。然而，关于药用植物来源的 ELNVs 的报道较少。
从（Lour.）Merr.（ACNVs）中分离和表征了 ELNVs。评估了 ACNVs 对肝癌细胞的细胞毒性、抗增殖和诱导凋亡能力。在存在不同内吞作用抑制剂的情况下，在 Hep G2 细胞上评估了 ACNVs 的内吞作用机制。在健康和荷瘤小鼠中，通过清除受体（SRs）阻断后检测 ACNVs 的体内分布。通过优化药代动力学特征，实现了 ACNVs 的聚乙二醇（PEG）工程化。在 Hep G2 细胞异种移植模型中评估了体内抗肿瘤活性和毒性。
使用差速离心法和蔗糖梯度超速离心法分离和纯化了 ACNVs。优化后的 ACNVs 平均粒径约为 119nm，呈现出典型的杯状纳米结构，包含脂质、蛋白质和 RNA。研究发现 ACNVs 具有特定的抗肿瘤细胞增殖活性，与诱导细胞凋亡的途径有关。ACNVs 可以通过吞噬作用进入肿瘤细胞，但一旦进入血液，它们很快被清除。阻断 SRs 或 PEG 化修饰可延长血液循环时间并增加 ACNVs 在肿瘤部位的积累。体内抗肿瘤结果表明，PEG 化 ACNVs 可显著抑制肿瘤生长，且无副作用。
本研究提供了一种有前途的功能性纳米平台，该平台来源于可食用的，可用于抗肿瘤治疗，副作用极小。
