Tumor Eradication by Boron Neutron Capture Therapy with 10B‐enriched Hexagonal Boron Nitride Nanoparticles Grafted with Poly(Glycerol)
Tumor Eradication by Boron Neutron Capture Therapy with 10B‐enriched Hexagonal Boron Nitride Nanoparticles Grafted with Poly(Glycerol)
复制标题
采用聚甘油接枝的富 10B 六方氮化硼纳米颗粒进行硼中子俘获疗法根除肿瘤
DOI：
10.1002/adma.202301479
复制
发表时间：
2023
影响因子：
29.4
通讯作者：
Li Zhao
中科院分区：
文献类型：
--
作者：
Yucai Zhang;H. Kang;Huazhen Xu;Honghui Luo;Minoru Suzuki;Qing Lan;Xiao Chen;N. Komatsu;Li Zhao
硼中子俘获治疗（BNCT）已成为一种治疗顽固性肿瘤的高精度和有效性的治疗方式。有效的肿瘤BNCT的核心是具有容易制备以及有利的药代动力学和治疗特性的10 B载体。在此，报告了用聚（甘油）（h-10 BN-PG）接枝的亚10 nm 10 B富集的六方氮化硼纳米颗粒的设计和制备，以及它们通过BNCT用于癌症治疗的应用。由于它们的小颗粒尺寸和突出的隐形特性，h-10 BN-PG纳米颗粒在小鼠CT 26结肠肿瘤中有效地积累，在注射后12小时具有8.8%ID g-1或102.1 µg g-1的高肿瘤内10 B浓度。此外，h-10 BN-PG纳米颗粒渗透到肿瘤实质内部，然后被肿瘤细胞吸收。包括h-10 BN-PG纳米颗粒的单次团注和随后的一次性中子照射的BNCT导致皮下CT 26肿瘤的显著收缩。h-10 BN-PG-介导的BNCT不仅对肿瘤细胞造成直接的DNA损伤，而且在肿瘤组织中引发明显的炎症免疫反应，这有助于中子照射后持久的肿瘤抑制。因此，h-10 BN-PG纳米颗粒是通过高效的10 B积累来根除肿瘤的有希望的BNCT剂。
Boron neutron capture therapy (BNCT) has emerged as a treatment modality with high precision and efficacy of intractable tumors. At the core of effective tumor BNCT are 10B carriers with facile preparation as well as advantageous pharmacokinetic and therapeutic profiles. Herein, the design and preparation of sub‐10 nm 10B‐enriched hexagonal boron nitride nanoparticles grafted with poly(glycerol) (h‐10BN‐PG), and their application to cancer treatment by BNCT are reported. By virtue of their small particle size and outstanding stealth property, h‐10BN‐PG nanoparticles accumulate efficiently in murine CT26 colon tumors with a high intratumor 10B concentration of 8.8%ID g−1 or 102.1 µg g−1 at 12 h post‐injection. Moreover, h‐10BN‐PG nanoparticles penetrate into the inside of the tumor parenchyma and then are taken up by the tumor cells. BNCT comprising a single bolus injection of h‐10BN‐PG nanoparticles and subsequent one‐time neutron irradiation results in significant shrinkage of subcutaneous CT26 tumors. h‐10BN‐PG‐mediated BNCT not only causes direct DNA damage to the tumor cells, but also triggers pronounced inflammatory immune response in the tumor tissues, which contributes to long‐lasting tumor suppression after the neutron irradiation. Thus, the h‐10BN‐PG nanoparticles are promising BNCT agents to eradicate tumor through highly efficient 10B accumulation.