A diaCEST MRI approach for monitoring liposomal accumulation in tumors.
A diaCEST MRI approach for monitoring liposomal accumulation in tumors.
复制标题
DOI：
10.1016/j.jconrel.2014.02.005
复制
发表时间：
2014-04-28
期刊：
影响因子：
--
通讯作者：
McMahon MT
中科院分区：
文献类型：
--
作者：
Chan KW;Yu T;Qiao Y;Liu Q;Yang M;Patel H;Liu G;Kinzler KW;Vogelstein B;Bulte JW;van Zijl PC;Hanes J;Zhou S;McMahon MT
基于纳米载体的化学疗法允许将治疗剂优先递送至肿瘤，并且已发现其改善癌症治疗的功效。然而，在追踪纳米载体和评估其在患者中的药理学命运方面的困难限制了对那些可能最受益于纳米治疗的患者的明智选择。为了能够在体内监测纳米载体，我们开发了MRI可追踪的抗磁性化学交换饱和转移（diaCEST）脂质体。diaCEST脂质体基于脂质体多柔比星（即DOXIL®）的临床制剂，并装载有巴比妥酸（BA），一种小的有机生物相容性diaCEST造影剂。BA与脂质比为25%的优化diaCEST脂质体制剂在体外B1=4.7 µT时显示出30%的对比度增强。对比度是稳定的，约80%的初始CEST信号在体外持续超过8小时。我们使用diaCEST脂质体监测对肿瘤坏死因子α（TNF-α）的反应，TNF-α是一种临床试验中的药物，可增加血管通透性和肿瘤对纳米载体的摄取。对携带CT 26肿瘤的小鼠全身给予diaCEST脂质体后，我们发现在B1=4.7 µT时BA频率（5 ppm）下的平均diaCEST对比度为0.4%，而如果同时给予TNF-α，对比度增加至1.5%。这种新方法提供了一种非放射性、非金属、生物相容性、半定量和临床可转化的方法来评估隐形脂质体在体内的肿瘤靶向，这可能使个性化纳米医学成为可能。
Nanocarrier-based chemotherapy allows preferential delivery of therapeutics to tumors and has been found to improve the efficacy of cancer treatment. However, difficulties in tracking nanocarriers and evaluating their pharmacological fate in patients have limited judicious selection of patients to those who might most benefit from nanotherapeutics. To enable the monitoring of nanocarriers in vivo, we developed MRI-traceable diamagnetic Chemical Exchange Saturation Transfer (diaCEST) liposomes. The diaCEST liposomes were based on the clinical formulation of liposomal doxorubicin (i.e. DOXIL®) and were loaded with barbituric acid (BA), a small, organic, biocompatible diaCEST contrast agent. The optimized diaCEST liposomal formulation with a BA-to-lipid ratio of 25% exhibited 30% contrast enhancement at B1=4.7 µT in vitro. The contrast was stable, with ~ 80% of the initial CEST signal sustained over 8 hrs in vitro. We used the diaCEST liposomes to monitor the response to tumor necrosis factoralpha (TNF-α), an agent in clinical trials that increases vascular permeability and uptake of nanocarriers into tumors. After systemic administration of diaCEST liposomes to mice bearing CT26 tumors, we found an average diaCEST contrast at the BA frequency (5 ppm) of 0.4% at B1=4.7 µT while if TNF-α was co-administered the contrast increased to 1.5%. This novel approach provides a non-radioactive, non-metallic, biocompatible, semi-quantitative and clinically translatable approach to evaluate the tumor targeting of stealth liposomes in vivo, which may enable personalized nanomedicine.
登录
查看更多内容
影响因子：
6.4
作者：
Brouckaert, P;Takahashi, N;Ten Hagen, TLM
通讯作者：
Ten Hagen, TLM
影响因子：
3.3
作者：
Jones, Craig K.;Polders, Daniel;Hua, Jun;Zhu, He;Hoogduin, Hans J.;Zhou, Jinyuan;Luijten, Peter;van Zijl, Peter C. M.
通讯作者：
van Zijl, Peter C. M.
DOI：
10.1016/0005-2736(91)90246-5
发表时间：
1991-07-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ALLEN, TM;HANSEN, C;YAUYOUNG, A
通讯作者：
YAUYOUNG, A
影响因子：
5.7
作者：
Jones, Craig K.;Huang, Alan;Xu, Jiadi;Edden, Richard A. E.;Schaer, Michael;Hua, Jun;Oskolkov, Nikita;Zaca, Domenico;Zhou, Jinyuan;McMahon, Michael T.;Pillai, Jay J.;van Zijl, Peter C. M.
通讯作者：
van Zijl, Peter C. M.
影响因子：
19.7
作者：
KABALKA, G;BUONOCORE, E;HUANG, L
通讯作者：
HUANG, L