Tumor Exosomes Reprogrammed by Low pH Are Efficient Targeting Vehicles for Smart Drug Delivery and Personalized Therapy against their Homologous Tumor.
Tumor Exosomes Reprogrammed by Low pH Are Efficient Targeting Vehicles for Smart Drug Delivery and Personalized Therapy against their Homologous Tumor.
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低pH值重编程的肿瘤外泌体是针对同源肿瘤的智能药物输送和个性化治疗的有效靶向载体
DOI：
10.1002/advs.202002787
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Ma G
中科院分区：
文献类型：
--
作者：
Gong C;Zhang X;Shi M;Li F;Wang S;Wang Y;Wang Y;Wei W;Ma G
作为膜结合的细胞外囊泡，外泌体具有针对特定细胞类型的靶向能力，并且细胞环境强烈影响其含量和摄取效率。受这些自然属性的启发，我们评估了各种细胞应激条件对肿瘤迭代外泌体摄取效率的影响，发现低pH处理可提高摄取效率并保留细胞类型特异性。脂质组学分析和分子动力学模拟揭示了基于甘油脂质自聚集的机制增强同源摄取。此外，这些低pH重编程的外泌体被开发成智能药物递送平台，其能够特异性地靶向肿瘤细胞，并通过近红外辐射触发的活性氧簇爆发来响应外泌体破裂而选择性地释放多种化学药物。该平台具有安全和增强的抗肿瘤作用，通过多个模型小鼠实验证明。这些结果开辟了一条新的途径来重新编程外泌体，以实现智能药物递送和针对其同源肿瘤的潜在个性化治疗。通过低pH条件处理的肿瘤外泌体可以增强其摄取效率，并基于基于甘油脂质自聚集的机制保留其亲本细胞的细胞类型特异性。它们被开发为智能药物递送平台，特异性地靶向肿瘤细胞，并响应近红外辐照选择性地释放多种化学药物，以实现安全和增强的抗肿瘤效果。
As membrane‐bound extracellular vesicles, exosomes have targeting ability for specific cell types, and the cellular environment strongly impacts their content and uptake efficiency. Inspired by these natural properties, the impacts of various cellular stress conditions on the uptake efficiency of tumor iterated exosomes are evaluated, and low‐pH treatment caused increased uptake efficiency and retained cell‐type specificity is found. Lipidomics analyses and molecular dynamics simulations reveal a glycerolipid self‐aggregation‐based mechanism for the enhanced homologous uptake. Furthermore, these low‐pH reprogrammed exosomes are developed into a smart drug delivery platform, which is capable of specifically targeting tumor cells and selectively releasing diverse chemodrugs in response to the exosome rupture by the near‐infrared irradiance‐triggered burst of reactive oxygen species. This platform exerts safe and enhanced antitumor effects demonstrated by multiple model mice experiments. These results open a new avenue to reprogram exosomes for smart drug delivery and potentially personalized therapy against their homologous tumor. Tumor exosomes treated by low‐pH condition can enhance their uptake efficiency and retain cell‐type specificity for their parent cells based on a glycerolipid self‐aggregation‐based mechanism. They are developed as a smart drug delivery platform, specifically targeting tumor cells and selectively releasing diverse chemodrugs in response to the near‐infrared irradiance, to achieve safe and enhanced antitumor effects.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
29.4
作者：
Sun, Huiping;Su, Jinghan;Li, Yaping
通讯作者：
Li, Yaping
影响因子：
37.3
作者：
Shao C;Yang F;Miao S;Liu W;Wang C;Shu Y;Shen H
通讯作者：
Shen H
影响因子：
3.8
作者：
King HW;Michael MZ;Gleadle JM
通讯作者：
Gleadle JM