Biodistribution and delivery efficiency of unmodified tumor-derived exosomes.
Biodistribution and delivery efficiency of unmodified tumor-derived exosomes.
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DOI：
10.1016/j.jconrel.2014.12.013
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发表时间：
2015-02-10
期刊：
影响因子：
--
通讯作者：
Anchordoquy TJ
中科院分区：
文献类型：
--
作者：
Smyth T;Kullberg M;Malik N;Smith-Jones P;Graner MW;Anchordoquy TJ
外泌体作为药物递送载体的用途已经获得了相当大的兴趣。为了确定外泌体是否可以有效地用于药物递送，必须更好地了解它们的体内命运。通过与脂质体制剂的比较，在过去的三十年里，脂质体制剂已经被广泛研究，我们能够对未修饰的肿瘤来源的外泌体在体内的命运做出一些全面的结论。我们观察到静脉内注射的外泌体、PC：Chol脂质体和用外泌体的脂质提取物配制的脂质体的相当的快速清除和最小的肿瘤蓄积，表明外泌体的独特蛋白质和脂质组成不会明显影响外泌体的清除率和生物分布。这种快速清除沿着未修饰的外来体的最小肿瘤蓄积限制了它们作为抗癌药物递送载体的用途;然而，当瘤内递送时，外来体保持与肿瘤组织缔合的程度显著大于PC：Chol脂质体。此外，利用具有受损的适应性或先天免疫系统的小鼠的实验揭示了先天免疫系统沿着补体蛋白C5对外泌体的清除速率的重要性。
The use of exosomes as a drug delivery vehicle has gained considerable interest. To establish if exosomes could be utilized effectively for drug delivery, a better understanding of their in vivo fate must be established. Through comparisons to liposomal formulations, which have been studied extensively for the last thirty years, we were able to make some comprehensive conclusions about the fate of unmodified tumor-derived exosomes in vivo. We observed a comparable rapid clearance and minimal tumor accumulation of intravenously-injected exosomes, PC:Chol liposomes, and liposomes formulated with the lipid extract of exosomes, suggesting the unique protein and lipid composition of exosomes does not appreciably impact exosomes’ rate of clearance and biodistribution. This rapid clearance along with minimal tumor accumulation of unmodified exosomes limits their use as an anti-cancer drug delivery vehicle; however, when delivered intratumorally, exosomes remained associated with tumor tissue to a significantly greater extent than PC:Chol liposomes. Furthermore, experiments utilizing mice with impaired adaptive or innate immune systems, revealed the significance of the innate immune system along with the complement protein C5 on exosomes’ rate of clearance.
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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.
影响因子：
21.3
作者：
Hergenreider, Eduard;Heydt, Susanne;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
3.9
作者：
Bradley, AJ;Devine, DV;Brooks, DE
通讯作者：
Brooks, DE
DOI：
10.1016/0005-2736(91)90268-d
发表时间：
1991-01-09
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ALLEN, TM;AUSTIN, GA;LEE, KC
通讯作者：
LEE, KC
DOI：
10.1073/pnas.85.18.6949
发表时间：
1988-09-01
影响因子：
11.1
作者：
GABIZON, A;PAPAHADJOPOULOS, D
通讯作者：
PAPAHADJOPOULOS, D