Department of Pharmaceutical Chemistry, University of Kansas, 2095 Constant Ave, Lawrence, KS 66047, USA.
Pharmaceutics. 2012 May 23;4(2):276-95. doi: 10.3390/pharmaceutics4020276.
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.
需要新的淋巴成像技术来更好地评估免疫功能和癌症的进展和治疗。淋巴摄取主要取决于颗粒大小（10-100nm）和电荷。成像和药物输送载体的大小可以进行优化，以最大限度地提高淋巴摄取，将化疗定位到淋巴转移部位，并使治疗沉积可视化。为此，雌性 BALB/c 小鼠在足底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-IR820）缀合物（约 5-200nm）。在两周内使用全身荧光成像对小鼠进行成像。在引流的淋巴管毛细血管以及腘窝和髂或腋窝淋巴结中清楚地观察到 HA-IR820 的荧光。74kDa 的 HA-IR820 具有最大的淋巴结 AUC。与之前的报道相反，与没有肿瘤的小鼠相比，携带肢体肿瘤的小鼠在腘窝淋巴结中保留了 74kDa 的 HA-IR820 长达三倍。通过改变其分子量，可以专门调整 HA 缀合物的动力学和分布。HA 缀合物的特异性淋巴摄取和增加的淋巴结保留表明其作为用于淋巴管内药物输送和成像的天然生物聚合物具有重要的开发潜力。
