Feasibility of Using Poly[oligo(ethylene glycol) Methyl Ether Methacrylate] as Tumor-Targeted Carriers of Diagnostic Drugs
Feasibility of Using Poly[oligo(ethylene glycol) Methyl Ether Methacrylate] as Tumor-Targeted Carriers of Diagnostic Drugs
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DOI：
10.1021/acsapm.2c00312
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发表时间：
2022-06-23
影响因子：
5
通讯作者：
Mukai, Takahiro
中科院分区：
文献类型：
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作者：
Sano, Kohei;Umemoto, Koki;Mukai, Takahiro
聚[低聚（乙二醇）甲基醚甲基丙烯酸酯]（POEGMA）是一种水溶性聚合物，其中多个短乙二醇（EG）链沿着疏水甲基丙烯酸甲酯主链接枝。我们研究了POEGMA是否可以用作肿瘤诊断的药物载体。为此，我们合成了具有不同分子量（11、21和30 kDa）和EG侧链长度的POEGMA衍生物，并用放射性同位素（铟-111; In-111）或荧光染料（吲哚菁绿色; ICG）标记它们作为信号发射体。使用ICG标记的POEGMA衍生物处理的colon 26肿瘤细胞的荧光显微镜研究显示，与对照聚乙二醇（PEG）相比，POEGMA衍生物被肿瘤细胞有效地摄取，这表明参与了POEGMA特异性细胞摄取途径。将放射性标记的POEGMA衍生物静脉注射到结肠26荷瘤小鼠中，并评价其生物分布。随着POEGMA衍生物分子量的增加，循环时间延长，其在肝脏和脾脏中的积累增加。特别是，21 kDa POEGMA显示出优异的肿瘤摄取和肿瘤与正常组织的比率。因此，我们研究了EG链长度对POEGMA（21 kDa）肿瘤摄取的影响，并观察到所有POEGMA衍生物的高肿瘤摄取;然而，对于EG链长度较长的POEGMA衍生物，观察到相对较高的腹部摄取。最后，在体内荧光成像使用优化的POEGMA衍生物标记ICG清楚地可视化肿瘤组织，这表明POEGMA衍生物可能是合适的药物载体敏感的肿瘤诊断。
Poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) is a water-soluble polymer in which multiple short ethylene glycol (EG) chains are grafted along the hydrophobic methyl methacrylate backbone. We investigated whether POEGMA could be used as a drug carrier for tumor diagnosis. For this purpose, we synthesized POEGMA derivatives with different molecular weights (11, 21, and 30 kDa) and EG side chain lengths, and labeled them with radioisotopes (indium-111; In-111) or fluorescence dyes (indocyanine green; ICG) as signal emitters. Fluorescence microscopy studies using colon26 tumor cells treated with ICG-labeled POEGMA derivatives revealed that the POEGMA derivatives were efficiently taken up by tumor cells compared to the control, poly(ethylene glycol) (PEG), suggesting the involvement of a POEGMA-specific cellular uptake pathway. The radiolabeled POEGMA derivatives were intravenously injected into colon26 tumor-bearing mice, and their biodistribution was evaluated. As the molecular weight of POEGMA derivatives increased, the circulating time was prolonged, and their accumulation in the liver and spleen increased. In particular, 21 kDa POEGMA showed excellent tumor uptake and tumor-to-normal tissue ratio. Therefore, we investigated the effect of EG chain length on the tumor uptake of POEGMA (21 kDa) and observed high tumor uptake for all POEGMA derivatives; however, relatively higher abdominal uptake was observed for POEGMA derivatives with longer EG chain lengths. Finally, in vivo fluorescence imaging using optimized POEGMA derivatives labeled with ICG clearly visualized the tumor tissues, suggesting that the POEGMA derivatives could be suitable drug carriers for sensitive tumor diagnosis.