Department of Materials Science and Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
ACS Nano. 2010 Mar 23;4(3):1279-87. doi: 10.1021/nn901297q.
The early diagnosis of cancer is the critical element in successful treatment and long-term favorable patient prognoses. The high rate of mortality is mainly attributed to the tendency for late diagnoses as symptoms may not occur until the disease has metastasized, as well as the lack of effective systemic therapies. Late diagnosis is often associated with the lack of timely sensitive imaging modalities. The promise of nanotechnology is presently limited by the inability to simultaneously seek, treat, and image cancerous lesions. This study describes the design and synthesis of fluorescent calcium phosphosilicate nanocomposite particles (CPNPs) that can be systemically targeted to breast and pancreatic cancer lesions. The CPNPs are a approximately 20 nm diameter composite composed of an amorphous calcium phosphate matrix doped with silicate in which a near-infrared imaging agent, indocyanine green (ICG), is embedded. In the present studies, we describe and validate CPNP bioconjugation of human holotransferrin, anti-CD71 antibody, and short gastrin peptides via an avidin-biotin or a novel PEG-maleimide coupling strategy. The conjugation of biotinylated human holotransferrin (diferric transferrin) and biotinylated anti-CD71 antibody (anti-transferrin receptor antibody) to avidin-conjugated CPNPs (Avidin-CPNPs) permits targeting of transferrin receptors, which are highly expressed on breast cancer cells. Similarly, the conjugation of biotinylated pentagastrin to Avidin-CPNPs and decagastrin (gastrin-10) to PEG-CPNPs via PEG-maleimide coupling permits targeting of gastrin receptors, which are overexpressed in pancreatic cancer lesions. These bioconjugated CPNPs have the potential to perform as a theranostic modality, simultaneously enhancing drug delivery, targeting, and imaging of breast and pancreatic cancer tumors.
癌症的早期诊断是成功治疗和长期预后良好的关键因素。高死亡率主要归因于晚期诊断，因为症状可能直到疾病转移才会出现，以及缺乏有效的全身治疗方法。晚期诊断通常与缺乏及时敏感的成像方式有关。纳米技术的前景目前受到限制，因为无法同时寻求、治疗和成像癌症病变。本研究描述了荧光钙磷硅纳米复合材料粒子（CPNPs）的设计和合成，这些粒子可以系统地靶向乳腺癌和胰腺癌病变。CPNPs 的直径约为 20nm，由掺杂硅的无定形磷酸钙基质组成，其中嵌入了近红外成像剂吲哚菁绿（ICG）。在本研究中，我们描述并验证了 CPNP 通过生物素化的人转铁蛋白、抗 CD71 抗体和短胃泌素肽与生物素化的人转铁蛋白（二价转铁蛋白）和生物素化的抗 CD71 抗体（抗转铁蛋白受体抗体）通过亲和素-生物素或新型 PEG-马来酰亚胺偶联策略偶联。将生物素化的人转铁蛋白（二价转铁蛋白）和生物素化的抗 CD71 抗体（抗转铁蛋白受体抗体）与亲和素偶联的 CPNP（Avidin-CPNP）偶联，可靶向转铁蛋白受体，转铁蛋白受体在乳腺癌细胞中高度表达。同样，通过 PEG-马来酰亚胺偶联将生物素化的五肽胃泌素与 Avidin-CPNP 偶联，将十肽胃泌素（胃泌素-10）与 PEG-CPNP 偶联，可靶向胃泌素受体，胃泌素受体在胰腺癌病变中过度表达。这些生物偶联的 CPNP 有可能成为一种治疗诊断学模式，同时增强乳腺癌和胰腺癌肿瘤的药物输送、靶向和成像。
