Institute of Pharmaceutical Technology, Biocenter Niederursel, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany; Wilhelimnenspital, Institute of Nuclear Medicine, Montleartstr. 37, 1160 Wien, Austria.
Department of Diagnostic Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
J Control Release. 2015 Sep 28;214:76-84. doi: 10.1016/j.jconrel.2015.07.017. Epub 2015 Jul 17.
Highly aggressive cancer types such as pancreatic cancer possess a mortality rate of up to 80% within the first 6months after diagnosis. To reduce this high mortality rate, more sensitive diagnostic tools allowing an early stage medical imaging of even very small tumours are needed. For this purpose, magnetic, biodegradable nanoparticles prepared using recombinant human serum albumin (rHSA) and incorporated iron oxide (maghemite, γ-Fe2O3) nanoparticles were developed. Galectin-1 has been chosen as target receptor as this protein is upregulated in pancreatic cancer and its precursor lesions but not in healthy pancreatic tissue nor in pancreatitis. Tissue plasminogen activator derived peptides (t-PA-ligands), that have a high affinity to galectin-1 have been chosen as target moieties and were covalently attached onto the nanoparticle surface. Improved targeting and imaging properties were shown in mice using single photon emission computed tomography-computer tomography (SPECT-CT), a handheld gamma camera, and magnetic resonance imaging (MRI).
高度侵袭性的癌症类型，如胰腺癌，在诊断后的头 6 个月内死亡率高达 80%。为了降低这种高死亡率，需要更敏感的诊断工具，以便在早期进行医学成像，即使是非常小的肿瘤。为此，使用重组人血清白蛋白（rHSA）和氧化铁（磁赤铁矿，γ-Fe2O3）纳米颗粒制备了磁性、可生物降解的纳米颗粒。选择半乳糖凝集素-1 作为靶受体，因为这种蛋白质在胰腺癌及其前体病变中上调，但在健康的胰腺组织和胰腺炎中不表达。组织纤溶酶原激活物衍生肽（t-PA 配体）与半乳糖凝集素-1 具有高亲和力，被选为靶部分，并共价连接到纳米颗粒表面。使用单光子发射计算机断层扫描-计算机断层扫描（SPECT-CT）、手持式伽马相机和磁共振成像（MRI）在小鼠中显示出了改进的靶向和成像特性。
