Impact of molecular weight on lymphatic drainage of a biopolymer-based imaging agent.
Impact of molecular weight on lymphatic drainage of a biopolymer-based imaging agent.
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DOI：
10.3390/pharmaceutics4020276
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发表时间：
2012-05-23
期刊：
影响因子：
5.4
通讯作者：
Forrest, Laird
中科院分区：
文献类型：
--
作者：
Bagby, Taryn R;Cai, Shuang;Forrest, Laird
需要新的淋巴成像技术来更好地评估免疫功能和癌症进展和治疗。淋巴吸收主要取决于颗粒大小（10-100 nm）和电荷。可以优化用于成像和药物递送的载体的尺寸，以最大化淋巴吸收，将化疗定位于淋巴转移，并使治疗沉积可视化。为此，在雌性BALB/c小鼠的后足垫或前臂皮下注射一系列六种不同分子量的透明质酸（HA）近红外染料（HA-IR 820）缀合物（约100 μ g）。5-200 nm）。使用全身荧光成像对小鼠进行两周成像。HA-IR 820荧光在引流毛细淋巴管中以及在腘和髂或腋淋巴结中清晰可见。74-kDa HA-IR 820具有最大的淋巴结曲线下面积。与先前的报道相反，与没有肿瘤的小鼠相比，携带肢体肿瘤的小鼠在腘淋巴结中表现出三倍长的74-kDa HA-IR 820保留。HA缀合物动力学和处置可以通过改变其分子量来具体定制。HA缀合物的特异性淋巴吸收和增加的淋巴结保留表明作为用于淋巴内药物递送和成像的天然生物聚合物的开发的显著潜力。
New lymphatic imaging technologies are needed to better assess immune function and cancer progression and treatment. Lymphatic uptake depends mainly on particle size (10-100 nm) and charge. The size of carriers for imaging and drug delivery can be optimized to maximize lymphatic uptake, localize chemotherapy to lymphatic metastases, and enable visualization of treatment deposition. Toward this end, female BALB/c mice were injected subcutaneously in the hind footpad or forearm with a series of six different molecular weight hyaluronan (HA) near-infrared dye (HA-IR820) conjugates (ca. 5-200 nm). Mice were imaged using whole body fluorescent imaging over two weeks. HA-IR820 fluorescence was clearly visualized in the draining lymphatic capillaries, and in the popliteal and iliac or axillary lymph nodes. The 74-kDa HA-IR820 had the largest lymph node area-under-the-curve. In contrast to prior reports, mice bearing limb tumors exhibited three-fold longer retention of 74-kDa HA-IR820 in the popliteal node compared to mice without tumors. HA conjugate kinetics and disposition can be specifically tailored by altering their molecular weight. The specific lymphatic uptake and increased nodal retention of HA conjugates indicate significant potential for development as a natural biopolymer for intralymphatic drug delivery and imaging.