title: Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas.
abstract: 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.
authors: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
authors: Congxin
authors: C
authors: Dai
authors: Feng
authors: F
authors: Cai
authors: Kuo Chu
authors: KC
authors: Hwang
authors: Yongmao
authors: Y
authors: Zhou
authors: Zizhu
authors: Z
authors: Zhang
authors: Xiaohai
authors: X
authors: Liu
authors: Sihai
authors: S
authors: Ma
authors: Yakun
authors: Y
authors: Yang
authors: Yong
authors: Y
authors: Yao
authors: Ming
authors: M
authors: Feng
authors: Xinjie
authors: X
authors: Bao
authors: Guilin
authors: G
authors: Li
authors: Junji
authors: J
authors: Wei
authors: Yonghui
authors: Y
authors: Jiao
authors: Zhenqing
authors: Z
authors: Wei
authors: Wenbin
authors: W
authors: Ma
authors: Renzhi
authors: R
authors: Wang
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D017209:Apoptosis / Q000528:radiation effects; D001895:Boron / Q000008:administration & dosage*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D002244:Carbon; D002470:Cell Survival / Q000528:radiation effects; D016503:Drug Delivery Systems; D058975:Folate Receptor 1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007554:Isotopes / Q000008:administration & dosage; D053758:Nanoparticles; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D007554:Isotopes; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D002244:Carbon; D001895:Boron