Simultaneous quantification of tumor uptake for targeted and nontargeted liposomes and their encapsulated contents by ICPMS.

Simultaneous quantification of tumor uptake for targeted and nontargeted liposomes and their encapsulated contents by ICPMS.
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DOI:
10.1021/ac301852y
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发表时间:
2012-09-04
影响因子:
7.4
通讯作者:
Tsourkas A
Tsourkas A
中科院分区:
化学1区
文献类型:
--
作者:
Cheng Z;Al Zaki A;Hui JZ;Tsourkas A

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脂质体正在被广泛地开发用于生物医学应用,包括药物和基因输送。然而,靶向脂质体在癌症治疗中的应用是一个非常复杂的多步骤过程。静脉给药时的不良脂质体生物分布和血液循环中的膜不稳定可能导致只有很小一部分货物到达肿瘤。因此,需要开发新的定量策略来跟踪脂质体递送系统,以提高治疗指数并降低全身毒性。在这里,我们开发了一种简单的、非辐射的方法来同时定量靶向和非靶向对照脂质体及其包裹的内容物对肿瘤的摄取。具体地说,将四种不同的螯合稀土金属分别包裹或表面结合到肿瘤靶向和非靶向脂质体上。然后将这两种脂质体同时注射到荷瘤小鼠体内,通过电感耦合等离子体质谱(ICP-MS)定量测定它们的肿瘤递送,以便进行直接比较。肿瘤对脂质体本身及其包裹的内容物的摄取与单独注射的靶向和非靶向脂质体制剂一致。
Liposomes are intensively being developed for biomedical applications including drug and gene delivery. However, targeted liposomal delivery in cancer treatment is a very complicated multi-step process. Unfavorable liposome biodistribution upon intravenous administration and membrane destabilization in blood circulation could result in only a very small fraction of cargo reaching the tumors. It would therefore be desirable to develop new quantitative strategies to track liposomal delivery systems to improve the therapeutic index and decrease systemic toxicity. Here, we developed a simple and non-radiative method to quantify the tumor uptake of targeted and non-targeted control liposomes as well as their encapsulated contents simultaneously. Specifically, four different chelated lanthanide metals were encapsulated or surface-conjugated onto tumor-targeted and non-targeted liposomes, respectively. The two liposome formulations were then injected into tumor-bearing mice simultaneously and their tumor delivery was determined quantitatively via inductively coupled plasma-mass spectroscopy (ICP-MS), allowing for direct comparisons. Tumor uptake of the liposomes themselves and their encapsulated contents were consistent with targeted and non-targeted liposome formulations that were injected individually.
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