Han Xiangjun, Taratula Oleh, St Lorenz Anna, Moses Abraham S, Albarqi Hassan A, Jahangiri Younes, Wu Qirun, Xu Ke, Taratula Olena, Farsad Khashayar
Department of Radiology, First Hospital of China Medical University Shenyang Liaoning 110001 P. R. China
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University Portland Oregon 97201 USA
RSC Adv. 2021 Sep 15;11(47):29486-29497. doi: 10.1039/d1ra05658a. eCollection 2021 Sep 1.
Peri-necrotic tumor regions have been found to be a source of cancer stem cells (CSC), important in tumor recurrence. Necrotic and peri-necrotic tumor zones have poor vascular supply, limiting effective exposure to systemically administered therapeutics. Therefore, there is a critical need to develop agents that can effectively target these relatively protected tumor areas. We have developed a multi-property nanoplatform with necrosis avidity, fluorescence imaging and X-ray tracking capabilities to evaluate its feasibility for therapeutic drug delivery. The developed nanoparticle consists of three elements: poly(ethylene glycol)--poly(ε-caprolactone) as the biodegradable carrier; hypericin as a natural compound with fluorescence and necrosis avidity; and gold nanoparticles for X-ray tracking. This reproducible nanoparticle has a hydrodynamic size of 103.9 ± 1.7 nm with a uniform spherical morphology (polydispersity index = 0.12). The nanoparticle shows safety with systemic administration and a stable 30 day profile. Intravenous nanoparticle injection into a subcutaneous tumor-bearing mouse and intra-arterial nanoparticle injection into rabbits bearing VX2 orthotopic liver tumors resulted in fluorescence and X-ray attenuation within the tumors. In addition, and histological analysis confirmed the accumulation of hypericin and gold in areas of necrosis and peri-necrosis. This nanoplatform, therefore, has the potential to enhance putative therapeutic drug delivery to necrotic and peri-necrotic areas, and may also have an application for monitoring early response to anti-tumor therapies.
已发现肿瘤坏死周边区域是癌症干细胞（CSC）的来源，对肿瘤复发至关重要。坏死及坏死周边肿瘤区域的血管供应较差，限制了全身给药治疗的有效作用。因此，迫切需要开发能够有效靶向这些相对受保护肿瘤区域的药物。我们开发了一种具有坏死亲和性、荧光成像和X射线追踪能力的多功能纳米平台，以评估其用于治疗性药物递送的可行性。所开发的纳米颗粒由三部分组成：聚（乙二醇）-聚（ε-己内酯）作为可生物降解载体；金丝桃素作为具有荧光和坏死亲和性的天然化合物；以及用于X射线追踪的金纳米颗粒。这种可重复制备的纳米颗粒的流体动力学尺寸为103.9±1.7nm，具有均匀的球形形态（多分散指数=0.12）。该纳米颗粒经全身给药显示出安全性，且具有30天的稳定状态。将纳米颗粒静脉注射到皮下荷瘤小鼠体内，以及将纳米颗粒动脉内注射到荷VX2原位肝肿瘤的兔体内，均导致肿瘤内出现荧光和X射线衰减。此外，组织学分析证实金丝桃素和金在坏死及坏死周边区域蓄积。因此，这种纳米平台有潜力增强向坏死及坏死周边区域的假定治疗性药物递送，并且可能也可用于监测抗肿瘤治疗的早期反应。
