Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas  

作　　者：DAI CongXin CAI Feng HWANG Kuo Chu ZHOU YongMao ZHANG ZiZhu LIU XiaoHai MA SiHai YANG YaKun YAO Yong FENG Ming BAO XinJie LI GuiLin WEI JunJi JIAO YongHui WEI ZhenQing MA WenBin WANG RenZhi 

机构地区：[1]Department of Neurosurgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College [2]Department of Chemistry,Tsing Hua University [3]China Zhongyuan Engineering Corporation,China National Nuclear Corporation [4]China Nuclear Industry Beijing 410 Hospital of China Institute of Atomic Energy

出　　处：《Science China(Life Sciences)》2013年第2期163-173,共11页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China (81072084)

摘　　要：Invasive nonfunctional pituitary adenomas （NFPAs） are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy （BNCT） is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor （FR）-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs ceils for BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring these new applications of BNCT for tumors, especially benign tumors.Invasive nonfunctional pituitary adenomas(NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery.Currently,no medications are clinically effective in the control of NFPA.Although radiation therapy and radiosurgery are useful to prevent tumor regrowth,they are frequently withheld because of severe complications.Boron neutron capture therapy(BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue.Folate receptor(FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis.In this study,FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas.After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons,the cell viability of NFPAs was significantly decreased,while apoptotic cells were simultaneously increased.However,cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells.The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT.In conclusion,FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for BNCT.Furthermore,our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy,while exploring these new applications of BNCT for tumors,especially benign tumors.

关 键 词：nonfunctional pituitary adenomas folate receptor NANOPARTICLES boron neutron capture therapy 

分 类 号：R736.4[医药卫生—肿瘤]