Zhang Xiaoying, Tang Wenjing, Wen Haoyu, Wu Ercan, Ding Tianhao, Gu Jie, Lv Zhongwei, Zhan Changyou
Department of Nuclear Medicine, The Affiliated Shanghai Tenth People's Hospital of Nanjing Medical University, Shanghai 200072, China.
Center of Medical Research and Innovation, Shanghai Pudong Hospital & Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 201399, China.
Pharmaceutics. 2022 Apr 15;14(4):868. doi: 10.3390/pharmaceutics14040868.
Lung metastasis of colorectal cancer is common in the clinic; however, precise targeting for the diagnosis and therapy purposes of those lung metastases remains challenging. Herein, cholera toxin subunit b (CTB) protein was chemically conjugated on the surface of PEGylated liposomes (CTB-sLip). Both human-derived colorectal cancer cell lines, HCT116 and HT-29, demonstrated high binding affinity and cellular uptake with CTB-sLip. In vivo, CTB-sLip exhibited elevated targeting capability to the lung metastasis of colorectal cancer in the model nude mice in comparison to PEGylated liposomes (sLip) without CTB modification. CTB conjugation induced ignorable effects on the interaction between liposomes and plasma proteins but significantly enhanced the uptake of liposomes by numerous blood cells and splenic cells, leading to relatively rapid blood clearance in BALB/c mice. Even though repeated injections of CTB-sLip induced the production of anti-CTB antibodies, our results suggested CTB-sLip as promising nanocarriers for the diagnosis of lung metastasis of colorectal cancer.
结直肠癌的肺转移在临床上很常见；然而，针对这些肺转移进行精确的诊断和治疗靶向仍然具有挑战性。在此，霍乱毒素亚基b（CTB）蛋白被化学偶联到聚乙二醇化脂质体（CTB-sLip）表面。人源结直肠癌细胞系HCT116和HT-29都表现出与CTB-sLip的高结合亲和力和细胞摄取。在体内，与未修饰CTB的聚乙二醇化脂质体（sLip）相比，CTB-sLip在裸鼠模型中对结直肠癌肺转移表现出更高的靶向能力。CTB偶联对脂质体与血浆蛋白之间的相互作用产生的影响可忽略不计，但显著增强了众多血细胞和脾细胞对脂质体的摄取，导致BALB/c小鼠体内血液清除相对较快。尽管重复注射CTB-sLip会诱导抗CTB抗体的产生，但我们的结果表明CTB-sLip是用于结直肠癌肺转移诊断的有前景的纳米载体。
