Departments of Neural and Behavioral Sciences and the Microscopy Imaging Core Facility, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
Int J Nanomedicine. 2021 Mar 19;16:2297-2309. doi: 10.2147/IJN.S295740. eCollection 2021.
Accurate tumor identification and staging can be difficult. Aptamer-targeted indocyanine green (ICG)-nanoparticles can enhance near-infrared fluorescent imaging of pancreatic and prostate tumors and could improve early cancer detection. This project explored whether calcium-phosphosilicate nanoparticles, also known as NanoJackets (NJs), that were bioconjugated with a tumor-specific targeting DNA aptamer could improve the non-invasive detection of pancreatic and prostate tumors.
Using in vivo near-infrared optical imaging and ex vivo fluorescence analysis, DNA aptamer-targeted ICG-loaded NJs were compared to untargeted NJs for detection of tumors.
Nanoparticles were bioconjugated with the DNA aptamer AP1153, which binds to the CCK-B receptor (CCKBR). Aptamer bioconjugated NJs were not significantly increased in size compared with unconjugated nanoparticles. AP1153-ICG-NJ accumulation in orthotopic pancreatic tumors peaked at 18 h post-injection and the ICG signal was cleared by 36 h with no evidence on uptake by non-tumor tissues. Ex vivo tumor imaging confirmed the aptamer-targeted NJs accumulated to higher levels than untargeted NJs, were not taken up by normal pancreas, exited from the tumor vasculature, and were well-dispersed throughout pancreatic and prostate tumors despite extensive fibrosis. Specificity for AP1153-NJ binding to the CCK-B receptor on pancreatic tumor cells was confirmed by pre-treating tumor-bearing mice with the CCK receptor antagonist proglumide. Proglumide pre-treatment reduced the in vivo tumoral accumulation of AP1153-NJs to levels comparable to that of untargeted NJs.
Through specific interactions with CCK-B receptors, tumor-targeted nanoparticles containing either ICG or rhodamine WT were well distributed throughout the matrix of both pancreatic and prostate tumors. Tumor-targeted NJs carrying various imaging agents can enhance tumor detection.
准确识别和分期肿瘤可能较为困难。适体靶向吲哚菁绿（ICG）-纳米颗粒可增强胰腺和前列腺肿瘤的近红外荧光成像，从而提高早期癌症的检测率。本项目旨在探讨经生物缀合肿瘤特异性靶向 DNA 适体的磷酸钙纳米颗粒（又称 NanoJackets，NJ）是否可改善胰腺和前列腺肿瘤的非侵入性检测。
通过体内近红外光学成像和离体荧光分析，比较了靶向 DNA 适体的 ICG 负载型 NJ 与非靶向型 NJ 对肿瘤的检测效果。
纳米颗粒经 DNA 适体 AP1153 生物缀合，该适体与胆囊收缩素-B 受体（CCKBR）结合。与未缀合的纳米颗粒相比，AP1153 缀合型 NJ 的粒径无显著增大。AP1153-ICG-NJ 在荷瘤胰腺组织中的积累在注射后 18 h 达到峰值，ICG 信号在 36 h 时被清除，且无证据表明非肿瘤组织摄取。离体肿瘤成像证实，与非靶向型 NJ 相比，AP1153 靶向 NJ 积累水平更高，不会被正常胰腺组织摄取，可从肿瘤血管中排出，且可在胰腺和前列腺肿瘤中均匀分布，尽管肿瘤组织中存在广泛纤维化。用胆囊收缩素受体拮抗剂丙谷胺预处理荷瘤小鼠，证实了 AP1153-NJ 与胰腺肿瘤细胞上的 CCK-B 受体的特异性结合。丙谷胺预处理降低了 AP1153-NJ 在体内的肿瘤积累，使其与非靶向型 NJ 的水平相当。
通过与 CCK-B 受体的特异性相互作用，载有 ICG 或罗丹明 WT 的肿瘤靶向纳米颗粒均匀分布于胰腺和前列腺肿瘤的基质中。携带各种成像剂的肿瘤靶向 NJ 可增强肿瘤的检测。
