Tumor vasculature-targeted (10)B delivery by an Annexin A1-binding peptide boosts effects of boron neutron capture therapy.
Tumor vasculature-targeted (10)B delivery by an Annexin A1-binding peptide boosts effects of boron neutron capture therapy.
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DOI：
10.1186/s12885-020-07760-x
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发表时间：
2021-01-15
期刊：
影响因子：
3.8
通讯作者：
Ohyama C
中科院分区：
文献类型：
--
作者：
Yoneyama T;Hatakeyama S;Sutoh Yoneyama M;Yoshiya T;Uemura T;Ishizu T;Suzuki M;Hachinohe S;Ishiyama S;Nonaka M;Fukuda MN;Ohyama C
对硼苯丙氨酸（10 BPA）是目前BNCT临床试验中使用的强效10 B药物。为了使BNCT成功，必须在几个小时内给予高剂量（500 mg/kg）的10 BPA。在这里，我们报告了快速，超低剂量给药后的肿瘤血管特异性膜联蛋白A1靶向IFLLWQR（IF 7）结合10 BPA或硼卡酸钠（10 BSH）的BNCT疗效。(1)静脉内注射到携带MBT 2膀胱肿瘤的小鼠中的任一种10 B药物的IF 7缀合物和通过即时γ射线分析分析的10 B在肿瘤和正常器官中的生物分布。(2)通过携带MBT 2膀胱肿瘤的C3 H/He小鼠和携带YTS-1肿瘤的裸鼠评估IF 7 - 10 B药物介导的BNCT的治疗效果。将任一10 B药物的IF 7 C缀合物静脉注射到携带MBT 2膀胱肿瘤的小鼠中，可促进10 B在肿瘤中的快速积聚并抑制肿瘤生长。此外，在人YTS-1膀胱癌小鼠模型中，以超低（10-20 mg/kg）剂量的IF 7 - 10 B药物介导的BNCT多次治疗显著抑制了肿瘤生长，肿瘤中Anxa 1表达增加，CD 8阳性淋巴细胞浸润增加。我们的结论是，IF 7作为一个有效的10 B通过肿瘤血管靶向肿瘤组织的运载工具，并可以作为一个相关的车辆BNCT药物。在线版本包含补充材料，可通过10.1186/s12885-020-07760-x获得。
p-Boronophenylalanine (10BPA) is a powerful 10B drug used in current clinical trials of BNCT. For BNCT to be successful, a high (500 mg/kg) dose of 10BPA must be administered over a few hours. Here, we report BNCT efficacy after rapid, ultralow-dose administration of either tumor vasculature-specific annexin A1-targeting IFLLWQR (IF7)-conjugated 10BPA or borocaptate sodium (10BSH). (1) IF7 conjugates of either 10B drugs intravenously injected into MBT2 bladder tumor-bearing mice and biodistribution of 10B in tumors and normal organs analyzed by prompt gamma-ray analysis. (2) Therapeutic effect of IF7-10B drug-mediated BNCT was assessed by either MBT2 bladder tumor bearing C3H/He mice and YTS-1 tumor bearing nude mice. Intravenous injection of IF7C conjugates of either 10B drugs into MBT2 bladder tumor-bearing mice promoted rapid 10B accumulation in tumor and suppressed tumor growth. Moreover, multiple treatments at ultralow (10–20 mg/kg) doses of IF7-10B drug-mediated BNCT significantly suppressed tumor growth in a mouse model of human YTS-1 bladder cancer, with increased Anxa1 expression in tumors and infiltration by CD8-positive lymphocytes. We conclude that IF7 serves as an efficient 10B delivery vehicle by targeting tumor tissues via the tumor vasculature and could serve as a relevant vehicle for BNCT drugs. The online version contains supplementary material available at 10.1186/s12885-020-07760-x.
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影响因子：
4.8
作者：
SCHNITZER, JE;LIU, J;OH, P
通讯作者：
OH, P
影响因子：
8.8
作者：
Nonaka M;Suzuki-Anekoji M;Nakayama J;Mabashi-Asazuma H;Jarvis DL;Yeh JC;Yamasaki K;Akama TO;Huang CT;Campos AR;Nagaoka M;Sasai T;Kimura-Takagi I;Suwa Y;Yaegashi T;Shibata TK;Sugihara K;Nishizawa-Harada C;Fukuda M;Fukuda MN
通讯作者：
Fukuda MN
影响因子：
64.8
作者：
Oh, P;Li, Y;Schnitzer, JE
通讯作者：
Schnitzer, JE
影响因子：
1.8
作者：
Chen, Fei;Xiao, Yichun;Jiang, Mengjun
通讯作者：
Jiang, Mengjun
DOI：
10.1007/s10967-015-4533-3
发表时间：
2016-06-01
影响因子：
1.6
作者：
Gu, Xiaobo;Jiang, Mengjun;Lin, Xiufeng
通讯作者：
Lin, Xiufeng