LAT1-Targeting Thermoresponsive Fluorescent Polymer Probes for Cancer Cell Imaging.
LAT1-Targeting Thermoresponsive Fluorescent Polymer Probes for Cancer Cell Imaging.
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DOI：
10.3390/ijms19061646
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发表时间：
2018-06-01
影响因子：
5.6
通讯作者：
Kanazawa H
中科院分区：
文献类型：
--
作者：
Matsuura M;Ohshima M;Hiruta Y;Nishimura T;Nagase K;Kanazawa H
l型氨基酸转运蛋白1 （LAT1）在癌细胞中的表达高于正常细胞。因此，LAT1靶向探针将是一种很有前途的癌细胞成像工具。本研究合成了基于聚（n -异丙基丙烯酰胺-co- n， n -二甲基丙烯酰胺）（P(NIPAAm-co-DMAAm)）的LAT1靶向热响应性荧光聚合物探针，并对其对LAT1的亲和力进行了评价。合成的聚合物探针与HeLa细胞上的LAT1相互作用，并研究了LAT1摄取底物之一l-[3H]-亮氨酸的抑制作用。l-酪氨酸偶联P（NIPAAm-co-DMAAm）抑制l-[3H]-亮氨酸的摄取，而P（NIPAAm-co-DMAAm）和l-苯丙氨酸偶联P（NIPAAm-co-DMAAm）则无此作用。结果表明，l-酪氨酸共轭聚合物对LAT1具有较高的亲和力。用荧光素-5-马来酰亚胺修饰末端聚合物基团，制备了荧光聚合物探针。在聚合物转变温度以上，观察到聚合物探针的细胞摄取，因为聚合物变得疏水，这增强了与细胞膜的相互作用。利用流式细胞术对荧光探针进行定量分析，发现l-酪氨酸偶联的P(NIPAAm-co-DMAAm)-FL比P(NIPAAm-co-DMAAm)-FL更早显示出更高的荧光强度。结果表明LAT1亲和位点促进了细胞摄取。所开发的靶向lat1的热响应性荧光聚合物探针有望用于癌细胞成像。
L-type amino acid transporter 1 (LAT1) is more highly expressed in cancer cells compared with normal cells. LAT1 targeting probes would therefore be a promising tool for cancer cell imaging. In this study, LAT1-targeting thermoresponsive fluorescent polymer probes based on poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P(NIPAAm-co-DMAAm)) were synthesized and their affinity for LAT1 was evaluated. The synthesized polymer probes interacted with LAT1 on HeLa cells, and inhibition of l-[3H]-leucine, one of the substrates for LAT1 uptake, was investigated. l-Tyrosine-conjugated P(NIPAAm-co-DMAAm) inhibited the uptake of l-[3H]-leucine, while P(NIPAAm-co-DMAAm) and l-phenylalanine-conjugated P(NIPAAm-co-DMAAm) did not. This result indicated that l-tyrosine-conjugated polymer has a high affinity for LAT1. The fluorescent polymer probes were prepared by modification of a terminal polymer group with fluorescein-5-maleimide (FL). Above the polymer transition temperature, cellular uptake of the polymer probes was observed because the polymers became hydrophobic, which enhanced the interaction with the cell membrane. Furthermore, quantitative analysis of the fluorescent probe using flow cytometry indicated that l-tyrosine-conjugated P(NIPAAm-co-DMAAm)-FL shows higher fluorescence intensity earlier than P(NIPAAm-co-DMAAm)-FL. The result suggested that cellular uptake was promoted by the LAT1 affinity site. The developed LAT1-targeting thermoresponsive fluorescent polymer probes are expected to be useful for cancer cell imaging.
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影响因子：
3.5
作者：
Khunweeraphong N;Nagamori S;Wiriyasermkul P;Nishinaka Y;Wongthai P;Ohgaki R;Tanaka H;Tominaga H;Sakurai H;Kanai Y
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8.8
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作者：
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通讯作者：
Mori, Masatomo
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影响因子：
5.8
作者：
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4.7
作者：
Akizawa, Hiromichi;Imajima, Mitsuo;Arano, Yasushi
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