Noninvasive detection of passively targeted poly(ethylene glycol) nanocarriers in tumors.
Noninvasive detection of passively targeted poly(ethylene glycol) nanocarriers in tumors.
复制标题
肿瘤中被动靶向聚乙二醇纳米载体的无创检测。
DOI：
10.1021/mp2003913
复制
发表时间：
2012
影响因子：
4.9
通讯作者：
Sinko,PatrickJ
中科院分区：
文献类型：
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作者：
Singh,Yashveer;Gao,Dayuan;Gu,Zichao;Li,Shike;Stein,Stanley;Sinko,PatrickJ
本研究使用SkinSkan荧光分光光度计和活体成像系统(IVIS)100非侵入性地研究了一系列聚乙二醇纳米载体的被动肿瘤分布潜力。制备了不同分子量(10、20、30、40和60 kDa)的荧光素偶联聚乙二醇纳米载体，并对其进行了表征。将纳米载体静脉注射给荷有4T1皮下肿瘤的雌性Balb/c小鼠。在体内测量了肿瘤和对侧皮肤(即对照部位)的被动分布(λexc，480 nm；λem，515-520 nm)。肿瘤的信号强度始终明显高于对侧。两种方法的结果趋势与肿瘤分布以分子量依赖的方式增加(10<；20<；30≪40≪60 kDa)是一致的。24 h未检测到10 kDa纳米载体，而96 h可检测到40-60 kDa纳米载体，24 h时30、40和60 kDa纳米载体在肿瘤中的被动分布分别是20 kDa纳米载体的2.1、5.3和4.1倍。在96h，60 kDa纳米载体的肿瘤分布是40 kDa纳米载体的1.5倍，因此，分子量接近或高于肾排斥极限的≥纳米载体(球状蛋白为45 kDa)的肿瘤分布显著高于肾排斥极限以下的载体(40和60 kDa)。动态光散射法测定聚乙二醇聚合物的流体动力学半径表明，流体动力学半径为≥8 nm的聚合物制备的纳米载体具有较高的肿瘤分布。体外质量平衡研究表明，纳米载体的组织分布顺序为肿瘤>；肺>；脾>；肝>；肾>；肌肉&心脏，从而验证了体内研究。目前的研究结果表明，肿瘤的非侵入性皮肤成像为初步筛选纳米载体肿瘤的分布药代动力学提供了一种可靠和快速的方法。
The present studies noninvasively investigate the passive tumor distribution potential of a series of poly(ethylene glycol) (PEG) nanocarriers using a SkinSkan spectrofluorometer and an In Vivo Imaging System (IVIS) 100. Fluorescein conjugated PEG nanocarriers of varying molecular weights (10, 20, 30, 40, and 60 kDa) were prepared and characterized. The nanocarriers were administered intravenously to female balb/c mice bearing subcutaneous 4T1 tumors. Passive distribution was measured in vivo (λexc, 480 nm; λem, 515–520 nm) from the tumor and a contralateral skin site (i.e., control site). The signal intensity from the tumor was always significantly higher than that from the contralateral site. Trends in results between the two methods were consistent with tumor distribution increasing in a molecular weight-dependent manner (10 < 20 < 30 ≪ 40 ≪ 60 kDa). The 10 kDa nanocarrier was not detected in tumors at 24 h, whereas 40–60 kDa nanocarriers were detected in tumors for up to 96 h. The 30, 40, and 60 kDa nanocarriers showed 2.1, 5.3, and 4.1 times higher passive distribution in tumors at 24 h, respectively, as compared to the 20 kDa nanocarrier. The 60 kDa nanocarrier exhibited 1.5 times higher tumor distribution than 40 kDa nanocarrier at 96 h. Thus, PEG nanocarriers (40 and 60 kDa) with molecular weights close to or above the renal exclusion limit, which for globular proteins is ≥45 kDa, showed significantly higher tumor distribution than those below it. The hydrodynamic radii of PEG polymers, measured using dynamic light scattering (DLS), showed that nanocarriers obtained from polymers with hydrodynamic radii ≥8 nm exhibited higher tumor distribution. Ex vivo mass balance studies revealed that nanocarrier tissue distribution followed the rank order tumor > lung > spleen > liver > kidney > muscle > heart, thus validating the in vivo studies. The results of the current studies suggest that noninvasive dermal imaging of tumors provides a reliable and rapid method for the initial screening of nanocarrier tumor distribution pharmacokinetics.