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硼中子俘获治疗增强的硼酸酯酯聚合物胶束：合成、稳定性和肿瘤抑制研究。

Boron Neutron Capture Therapy Enhanced by Boronate Ester Polymer Micelles: Synthesis, Stability, and Tumor Inhibition Studies.

机构信息

Department of Material Science and Engineering, National Tsing Hua University, Hsinchu City 300, Taiwan.

出版信息

Biomacromolecules. 2024 Jul 8;25(7):4215-4232. doi: 10.1021/acs.biomac.4c00298. Epub 2024 Jun 6.

DOI:10.1021/acs.biomac.4c00298
PMID:38845149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11238341/
Abstract

Boron neutron capture therapy (BNCT) targets invasive, radioresistant cancers but requires a selective and high B-10 loading boron drug. This manuscript investigates boron-rich poly(ethylene glycol)--(poly(4-vinylphenyl boronate ester)) polymer micelles synthesized via atom transfer radical polymerization for their potential application in BNCT. Transmission electron microscopy (TEM) revealed spherical micelles with a uniform size of 43 ± 10 nm, ideal for drug delivery. Additionally, probe sonication proved effective in maintaining the micelles' size and morphology postlyophilization and reconstitution. In vitro studies with B16-F10 melanoma cells demonstrated a 38-fold increase in boron accumulation compared to the borophenylalanine drug for BNCT. In vivo studies in a B16-F10 tumor-bearing mouse model confirmed enhanced tumor selectivity and accumulation, with a tumor-to-blood (T/B) ratio of 2.5, surpassing BPA's T/B ratio of 1.8. As a result, mice treated with these micelles experienced a significant delay in tumor growth, highlighting their potential for BNCT and warranting further research.

摘要

硼中子俘获治疗（BNCT）针对侵袭性、抗辐射性癌症，但需要一种选择性高且硼-10 负载量高的硼药物。本文研究了通过原子转移自由基聚合合成的富含硼的聚乙二醇-（聚（4-乙烯基苯硼酸酯））聚合物胶束，以探讨其在 BNCT 中的潜在应用。透射电子显微镜（TEM）显示出具有 43±10nm 均匀尺寸的球形胶束，非常适合药物输送。此外，探针超声处理在冷冻干燥和再形成后有效地维持了胶束的尺寸和形态。用 B16-F10 黑色素瘤细胞进行的体外研究表明，与硼苯丙氨酸药物相比，硼积累增加了 38 倍，可用于 BNCT。在 B16-F10 荷瘤小鼠模型中的体内研究证实了增强的肿瘤选择性和积累，肿瘤与血液（T/B）的比率为 2.5，超过了 BPA 的 T/B 比率 1.8。因此，用这些胶束治疗的小鼠肿瘤生长明显延迟，突出了它们在 BNCT 中的潜力，值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2064/11238341/5873792196cb/bm4c00298_0013.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2064/11238341/8d07f67883c1/bm4c00298_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2064/11238341/446ddce296ad/bm4c00298_0009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2064/11238341/5873792196cb/bm4c00298_0013.jpg

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