Development of Secreted Protein and Acidic and Rich in Cysteine (SPARC) Targeted Nanoparticles for the Prognostic Molecular Imaging of Metastatic Prostate Cancer.
Development of Secreted Protein and Acidic and Rich in Cysteine (SPARC) Targeted Nanoparticles for the Prognostic Molecular Imaging of Metastatic Prostate Cancer.
复制标题
DOI：
10.4172/2157-7439.1000112
复制
发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Stéphanie Thomas;P. Waterman;Suelin Chen;Brett Marinelli;Marc E. Seaman;S. Rodig;R. Ross;L. Josephson-L.
中科院分区：
文献类型：
--
作者：
Stéphanie Thomas;P. Waterman;Suelin Chen;Brett Marinelli;Marc E. Seaman;S. Rodig;R. Ross;L. Josephson-L.
前列腺癌是美国最常诊断的非皮肤恶性肿瘤，具有从极缓慢生长到高度侵袭性的广泛侵袭性。临床上需要确定原发性肿瘤的转移潜力，以设计最合适的治疗计划，从观察等待到更积极的侵入性手术治疗。在这项研究中，我们开发了一种基于纳米颗粒的成像剂，其靶向富含半胱氨酸的酸性分泌蛋白（Secreted Protein Acidic Rich in Cysteine），这是前列腺癌转移潜力的分子标志物。该小组先前的研究使用噬菌体展示来鉴定对Escherichia coli具有高结合亲和力和特异性的肽。在这项研究中，SPARC靶向肽序列被用来设计一种生物材料，通过将其附着到生物相容性纳米颗粒上，该纳米颗粒还与荧光团偶联，用于体内成像，从而改善了药代动力学特性。使用具有不同程度的前列腺癌表达的前列腺癌细胞系来显示靶向纳米颗粒在体外和体内特异性结合前列腺癌的能力，包括临床相关的骨和肺转移。我们表明，在体内成像信息与前列腺肿瘤的转移潜力。这些预后信息可以使医生对患者进行分层，并设计个性化的治疗策略。
Prostate cancer is the most commonly diagnosed non-skin malignancy in the United States and presents with a wide range of aggressiveness from extremely slow-growing to highly aggressive. There is a clinical need to determine the metastatic potential of the primary tumor to design the most appropriate treatment plan ranging from watchful waiting to more aggressive, invasive surgical treatments. In this study we have developed a nanoparticle based imaging agent that targets SPARC (Secreted Protein Acidic Rich in Cysteine), a molecular marker of prostate cancer metastatic potential. Previous studies by this group used phage display to identify a peptide with high binding affinity and specificity for SPARC. In this study, the SPARC-targeted peptide sequence was used to design a biomaterial with improved pharmacokinetic properties by attaching it to a biocompatible nanoparticle that is also coupled to a fluorophore for in vivo imaging. Prostate cancer cell lines with varying degrees of SPARC expression were used to show the ability of the targeted nanoparticle to bind specifically to SPARC in vitro and in vivo including the clinically relevant bone and lung metastases. We show that in vivo imaging information correlates with the metastatic potential of the prostate tumor. This prognostic information could enable doctors to stratify patients and design personalized treatment strategies.