Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes.
Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes.
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超声触发局部递送Bmp7 mRNA，通过工程智能外泌体诱导白色脂肪褐化。
DOI：
10.1186/s12951-021-01145-3
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发表时间：
2021-12-04
影响因子：
10.2
通讯作者：
Yuan L
中科院分区：
文献类型：
--
作者：
Guo Y;Wan Z;Zhao P;Wei M;Liu Y;Bu T;Sun W;Li Z;Yuan L
高效和局部给药对于最大限度地提高疗效和最大限度地减少毒性至关重要。在这项研究中，我们的目标是设计一种基于外切体的药物传递平台，该平台具有逃避非靶器官的吞噬作用和在靶点可控地释放药物的能力。通过多肽CP05与胞外体表面标记CD63的相互作用，合成了可交换隐身涂层CP05-TK-mpeg。通过直接孵育的方法将三氯乙烷(Ce6)负载到外切体中。利用Ce6在超声辐射下产生的活性氧(ROS)破坏硫代缩酮(TK)，可以实现对聚乙二醇单甲醚的可控去除。整个平台被称为SmartExo。通过示踪外切体对RAW264.7细胞和C57BL/6小鼠的隐身效果进行了分析。为了证实构建的SMART外切体的有效性，将骨形态发生蛋白7(Bmp7)基因通过高表达的载体导入外切体，然后进行隐形包衣，将外切体命名为SmartExo@Bmp7。通过将Bmp7mRNA靶向肥胖C57BL/6小鼠的大网膜脂肪组织(OAT)诱导褐变，证实了SmartExo@Bmp7的治疗优势。在不改变外切体基本特性的情况下，成功构建了SmartExo平台。工程外切体能有效地逃脱RAW264.7和非靶器官的吞噬作用。此外，SmartExo可以根据当地的需要，通过超声波中介去除隐形涂层。与对照外切体相比，SmartExo@Bmp7能有效地将Bmp7mRNA导入燕麦，并诱导燕麦褐变，OAT的组织学和解偶联蛋白1(Ucp1)的表达增加证明了这一点。拟议的基于SmartExo的递送平台将副作用降至最低，并使药物功效最大化，为靶向递送药物提供了一种新的安全和高效的方法。作为证据，SmartExo@Bmp7诱导了局部白色脂肪组织的褐变，这将是一种有前景的减肥治疗策略。网上版载有补充材料，可在10.1186/s12951-021-01145-3查阅。
Efficient and topical delivery of drugs is essential for maximized efficacy and minimized toxicity. In this study, we aimed to design an exosome-based drug delivery platform endowed with the ability of escaping from phagocytosis at non-target organs and controllably releasing drugs at targeted location. The swtichable stealth coat CP05-TK-mPEG was synthesized and anchored onto exosomes through the interaction between peptide CP05 and exosomal surface marker CD63. Chlorin e6 (Ce6) was loaded into exosomes by direct incubation. Controllable removal of PEG could be achieved by breaking thioketal (TK) through reactive oxygen species (ROS), which was produced by Ce6 under ultrasound irradiation. The whole platform was called SmartExo. The stealth effects were analyzed in RAW264.7 cells and C57BL/6 mice via tracing the exosomes. To confirm the efficacy of the engineered smart exosomes, Bone morphogenetic protein 7 (Bmp7) mRNA was encapsulated into exosomes by transfection of overexpressing plasmid, followed by stealth coating, with the exosomes designated as SmartExo@Bmp7. Therapeutic advantages of SmartExo@Bmp7 were proved by targeted delivering Bmp7 mRNA to omental adipose tissue (OAT) of obese C57BL/6 mice for browning induction. SmartExo platform was successfully constructed without changing the basic characteristics of exosomes. The engineered exosomes effectively escaped from the phagocytosis by RAW264.7 and non-target organs. In addition, the SmartExo could be uptaken locally on-demand by ultrasound mediated removal of the stealth coat. Compared with control exosomes, SmartExo@Bmp7 effectively delivered Bmp7 mRNA into OAT upon ultrasound irradiation, and induced OAT browning, as evidenced by the histology of OAT and increased expression of uncoupling protein 1 (Ucp1). The proposed SmartExo-based delivery platform, which minimizes side effects and maximizing drug efficacy, offers a novel safe and efficient approach for targeted drug delivery. As a proof, the SmartExo@Bmp7 induced local white adipose tissue browning, and it would be a promising strategy for anti-obesity therapy. The online version contains supplementary material available at 10.1186/s12951-021-01145-3.
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影响因子：
12.4
作者：
Bellavia D;Raimondo S;Calabrese G;Forte S;Cristaldi M;Patinella A;Memeo L;Manno M;Raccosta S;Diana P;Cirrincione G;Giavaresi G;Monteleone F;Fontana S;De Leo G;Alessandro R
通讯作者：
Alessandro R
影响因子：
3.7
作者：
Li J;Chen X;Yi J;Liu Y;Li D;Wang J;Hou D;Jiang X;Zhang J;Wang J;Zen K;Yang F;Zhang CY;Zhang Y
通讯作者：
Zhang Y
DOI：
10.1097/med.0b013e328337a81f
发表时间：
2010-04
期刊：
Current opinion in endocrinology, diabetes, and obesity
影响因子：
--
作者：
Cypess AM;Kahn CR
通讯作者：
Kahn CR
外泌体作为帕金森氏病疗法的药物。
DOI：
10.1016/j.jconrel.2015.03.033
发表时间：
2015-06-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Haney MJ;Klyachko NL;Zhao Y;Gupta R;Plotnikova EG;He Z;Patel T;Piroyan A;Sokolsky M;Kabanov AV;Batrakova EV
通讯作者：
Batrakova EV
影响因子：
8.3
作者：
Chang, CF;Lin, SZ;Wang, Y
通讯作者：
Wang, Y