Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
Acta Biomater. 2018 May;72:256-265. doi: 10.1016/j.actbio.2018.03.035. Epub 2018 Mar 26.
Precise diagnosis of lymph node metastasis to guide lymphadenectomy is highly important for gastric cancer therapy in clinics. Though surgical dissection of regional metastatic lymph nodes remains the only way for gastric cancer therapy, the extended dissection may cause unavoidable postoperative risk of complications. It is still lack of effective method enabling the accurate removal of metastatic gastric cancer cells in lymph nodes with minimum injuries to normal tissue. Herein, we report a new fluorescent copper sulfide (CuS) nanoparticle (RGD-CuS-Cy5.5) enabling both non-invasive multimodality imaging and targeting photothermal therapy (PTT) of metastatic gastric cancer cells in lymph nodes. We demonstrate that RGD-CuS-Cy5.5 can easily drain into sentinel lymph nodes (SLN) after injection into primary tumors, and selectively enter into metastatic gastric MNK45 tumor cells via αβ integrin-mediated endocytosis. The resulting strong near-infrared (NIR) fluorescence and computed tomography (CT) contrast in metastatic SLN compared to normal SLN can precisely differentiate SLN metastasis of gastric cancers. Guided by the imaging, localized PTT with RGD-CuS-Cy5.5 is conducted upon irradiation with an 808 nm laser, resulting in complete removal of metastatic gastric tumor cells in SLN without obvious toxicity. Moreover, RGD-CuS-Cy5.5 can also allow for the rapid and non-invasive self-monitoring of PTT efficacy against metastatic SLNs in living mice. This study highlights the potential of using RGD-CuS-Cy5.5 for imaging-guided and targeting PTT of SLN metastasis in vivo, which may be applicable for the metastatic gastric cancer therapy in clinics.
RGD-CuS-Cy5.5 nanoparticles possess NIR fluorescence and CT signals for in vivo bimodality imaging of lymph node metastasis. Strong photothermal property under irradiation at 808 nm for efficient PTT. Easy drain into sentinel lymph nodes and selective enter metastatic gastric cancer cells via αβ integrin-mediated endocytosis. Rapid and non-invasive monitoring of therapeutic efficacy against lymph node metastasis.
准确诊断淋巴结转移以指导淋巴结清扫术对胃癌的临床治疗非常重要。虽然区域转移性淋巴结的外科解剖仍然是胃癌治疗的唯一方法，但广泛的解剖可能会导致不可避免的术后并发症风险。目前仍然缺乏一种有效的方法，能够在对正常组织最小损伤的情况下，准确地去除淋巴结中的转移性胃癌细胞。在此，我们报告了一种新的荧光硫化铜（CuS）纳米颗粒（RGD-CuS-Cy5.5），它能够实现转移性胃癌细胞的非侵入性多模态成像和靶向光热治疗（PTT）。我们证明，RGD-CuS-Cy5.5 可以在注射到原发肿瘤后轻松进入前哨淋巴结（SLN），并通过 αβ 整合素介导的内吞作用选择性进入转移性胃癌 MNK45 肿瘤细胞。与正常 SLN 相比，转移性 SLN 中产生的强烈近红外（NIR）荧光和计算机断层扫描（CT）对比，可以准确地区分胃癌的 SLN 转移。在 808nm 激光照射下，通过 RGD-CuS-Cy5.5 进行成像引导的局部 PTT，可完全去除 SLN 中的转移性胃癌肿瘤细胞，且无明显毒性。此外，RGD-CuS-Cy5.5 还可以允许对活体小鼠中的转移性 SLN 进行快速、非侵入性的 PTT 疗效的自我监测。本研究强调了使用 RGD-CuS-Cy5.5 进行体内 SLN 转移的成像引导和靶向 PTT 的潜力，这可能适用于临床中的转移性胃癌治疗。
