Article(id=1198624474955346551, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1198624466902287155, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2022-1089, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1664812800000, receivedDateStr=2022-10-04, revisedDate=1675699200000, revisedDateStr=2023-02-07, acceptedDate=null, acceptedDateStr=null, onlineDate=1763703944195, onlineDateStr=2025-11-21, pubDate=1681228800000, pubDateStr=2023-04-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1763703944195, onlineIssueDateStr=2025-11-21, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1763703944195, creator=13701087609, updateTime=1763703944195, updator=13701087609, issue=Issue{id=1198624466902287155, tenantId=1146029695717560320, journalId=1189982191388893191, year='2023', volume='58', issue='4', pageStart='1', pageEnd='1092', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1763703942275, creator=13701087609, updateTime=1763704125380, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1198625234971619912, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1198624466902287155, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1198625234971619913, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1198624466902287155, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=852, endPage=855, ext={EN=ArticleExt(id=1198624475370582686, articleId=1198624474955346551, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Advance on anti-tumor theranostics and biosafety of bismuth-based nanomedicine, columnId=null, journalTitle=Acta Pharmaceutica Sinica, columnName=null, runingTitle=null, highlight=null, articleAbstract=

Nanomedicine is one of the most promising fields in biomedicine. Inorganic nanomaterials stand out among many nanomaterials due to their excellent physicochemical properties, stable chemical properties and high biocompatibility. As an inorganic nanomaterial, bismuth-based nanomaterials have the advantages of adjustable band gap, low toxicity, easy functionalization, large X-ray attenuation coefficient, high photothermal conversion efficiency and long cycle half-life, so they have good promising application in cancer diagnosis and treatment. This review summarizes the recent research progress of bismuth-based nanomaterials in tumor diagnosis, treatment and biosafety, which provides a theoretical basis for the design and exploitation of a new generation of bismuth-based nanomedicine systems.

, correspAuthors=Lei-jiao LI, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2023 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Ying-jie WANG, Ping GAO, Meng SUN, Lei-jiao LI), CN=ArticleExt(id=1198624475882287825, articleId=1198624474955346551, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=铋基纳米药物系统的抗肿瘤诊疗及生物安全性研究进展, columnId=1198624468278018876, journalTitle=药学学报, columnName=专题报道: 纳米药物药代动力学研究, runingTitle=null, highlight=null, articleAbstract=

纳米生物医学是生物医药领域中最具有应用前景的方向之一, 无机纳米材料由于其优良的物理、化学特性、稳定的化学性质以及高生物相容性, 在众多的纳米材料中脱颖而出。作为一种低成本的无机纳米材料, 铋基纳米材料由于具有带隙可调、低毒性、易于功能化、较大X射线衰减系数、较高光热转换效率和长循环半衰期等优势, 在癌症诊断和治疗方面具有种种潜在的用途和广阔的应用前景。本文综述了铋基纳米材料在肿瘤诊断、治疗和生物安全性方面的最新研究进展, 为新一代铋基纳米药物系统的设计和开发提供理论依据和开发思路。

, correspAuthors=李磊姣, authorNote=null, correspAuthorsNote=
*李磊姣,Tel: 13620781946, E-mail:
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铋基纳米药物系统的抗肿瘤诊疗及生物安全性研究进展
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王英杰 , 高平 , 孙萌 , 李磊姣 *
药学学报 | 专题报道: 纳米药物药代动力学研究 2023,58(4): 852-855
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药学学报 | 专题报道: 纳米药物药代动力学研究 2023, 58(4): 852-855
铋基纳米药物系统的抗肿瘤诊疗及生物安全性研究进展
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王英杰, 高平, 孙萌, 李磊姣*
作者信息
  • 长春理工大学化学与环境工程学院, 吉林 长春 130022

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*李磊姣,Tel: 13620781946, E-mail:
Advance on anti-tumor theranostics and biosafety of bismuth-based nanomedicine
Ying-jie WANG, Ping GAO, Meng SUN, Lei-jiao LI*
Affiliations
  • School of Chemistry and Environmental Engineering, Changchun University of Science and Technology, Changchun 130022, China
出版时间: 2023-04-12 doi: 10.16438/j.0513-4870.2022-1089
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纳米生物医学是生物医药领域中最具有应用前景的方向之一, 无机纳米材料由于其优良的物理、化学特性、稳定的化学性质以及高生物相容性, 在众多的纳米材料中脱颖而出。作为一种低成本的无机纳米材料, 铋基纳米材料由于具有带隙可调、低毒性、易于功能化、较大X射线衰减系数、较高光热转换效率和长循环半衰期等优势, 在癌症诊断和治疗方面具有种种潜在的用途和广阔的应用前景。本文综述了铋基纳米材料在肿瘤诊断、治疗和生物安全性方面的最新研究进展, 为新一代铋基纳米药物系统的设计和开发提供理论依据和开发思路。

铋基纳米材料  /  肿瘤  /  诊断  /  治疗  /  生物安全性

Nanomedicine is one of the most promising fields in biomedicine. Inorganic nanomaterials stand out among many nanomaterials due to their excellent physicochemical properties, stable chemical properties and high biocompatibility. As an inorganic nanomaterial, bismuth-based nanomaterials have the advantages of adjustable band gap, low toxicity, easy functionalization, large X-ray attenuation coefficient, high photothermal conversion efficiency and long cycle half-life, so they have good promising application in cancer diagnosis and treatment. This review summarizes the recent research progress of bismuth-based nanomaterials in tumor diagnosis, treatment and biosafety, which provides a theoretical basis for the design and exploitation of a new generation of bismuth-based nanomedicine systems.

bismuth-based nanomaterial  /  tumor  /  diagnosis  /  therapy  /  biosafety
王英杰, 高平, 孙萌, 李磊姣. 铋基纳米药物系统的抗肿瘤诊疗及生物安全性研究进展. 药学学报, 2023 , 58 (4) : 852 -855 . DOI: 10.16438/j.0513-4870.2022-1089
Ying-jie WANG, Ping GAO, Meng SUN, Lei-jiao LI. Advance on anti-tumor theranostics and biosafety of bismuth-based nanomedicine[J]. Acta Pharmaceutica Sinica, 2023 , 58 (4) : 852 -855 . DOI: 10.16438/j.0513-4870.2022-1089
癌症是威胁人类生命最严重的疾病之一, 由于癌症的复杂性、多样性和异质性, 给诊断和治疗手段的更新和发展造成了巨大的障碍。近年来, 纳米材料在生物医学领域发挥着越来越重要的作用, 为癌症的诊断和治疗创造了新的发展机遇[1]。基于纳米光敏剂的光学抗肿瘤疗法, 是一类新兴的治疗方法, 即在光刺激下, 会引起局部过热(ΔT大于10 ℃) 或原位生成活性物质ROS (•OH、•O2-1O2等), 进而破坏癌细胞的DNA、蛋白质和脂质, 诱导癌细胞死亡[2]
近年来, 研究人员开发了大量可以被近红外光活化的金属基纳米制剂, 这些金属基纳米制剂对近红外光吸收能力强, 可以迅速将光能转化为热能或化学能, 实现精准治疗, 在抗肿瘤领域拥有巨大的优势。作为一种低成本的无机材料, Bi具有较大的X射线衰减系数(在100 keV辐射下, Bi: 5.74、Au: 5.16、Pt: 4.99和Ta: 4.3 cm2·g-1) 和较高的原子数(Bi: 83、Au: 79、Pt: 78、Ta: 72), 对X射线有最有效的吸收, 使其成为敏化放疗、光声成像制剂、光热成像、计算机X射线体层成像造影剂的理想选择。因此, 本文综述了不同类型的铋基纳米材料在抗肿瘤领域的应用情况, 并关注了铋基纳米材料在体内的分布和清除途径, 最后对该领域在未来面临的机遇和挑战进行了分析和讨论。图 1为铋基纳米材料在肿瘤诊疗方面的应用。
受到小尺寸纳米颗粒比大尺寸纳米颗粒具有更高X射线衰减效应的启发, Ai等[3]制备了一种直径约为2~3 nm的超小Bi2S3纳米点, 其计算机X射线体层成像能力明显高于临床使用的碘化剂。
由于二维纳米材料的载流子迁移和热量扩散都被限制在二维平面内, 它们展现出许多特殊的性质。Song等[4]通过调控乙二胺四乙酸的投入量, 实现了Bi2Te3纳米板的制备。乙二胺四乙酸和Bi3+的摩尔比为1∶1时, 产物为不规则的六方结构, 乙二胺四乙酸和Bi3+的摩尔比为4∶1时, 产物为均质的六方结构纳米板, 研究表明不规则的六方纳米板在肝脏内完成代谢和解毒; 而均质的六方结构纳米板由于尺寸小, 优先在肾脏内累积, 并被分解为金属离子以Te2-、Bi2+、Bi3+的形式随尿液排出体外。
Cheng等[5]制备了AgBiS2纳米颗粒, 近红外光敏化下可产生ROS, 实现对高度恶性骨肉瘤的光热/光动力学联合治疗。Chen等[6]研究制备了一种由小纳米颗粒组成的空心AgBiS2纳米球, 可以在细胞内产生1O2和•OH, 同步完成肿瘤的光热成像/光声成像和光热/光动力学治疗。
已报道的铋基纳米材料采用的激发光源功率大多在0.5~2 W·cm-2内, 然而, 这一强度的激光远高于皮肤耐受阈值(350 mW·cm-2)。因此, 低辐射光源强度、短辐射时间获得高抑瘤效果, 是研究人员的追寻目标之一。Kumar等[7]制备了在功率为10 mW·cm-2的808 nm近红外光激发下, 光热/光动力学协同抗肿瘤效果良好的Cu3BiS3纳米晶。治疗两周后, 小鼠的主要器官和血液中没有Cu3BiS3纳米晶残留, 说明已全部代谢出体内。组织染色结果分析证明各器官没有明显损伤。血清生化结果表明, 除了酸脱氢酶水平略有升高外, 其余的生化指标均未发生显著异常。上述结果均说明该材料具有生物安全性。
近红外Ⅱ区(1 000~1 700 nm, NIR-Ⅱ) 与近红外Ⅰ区(700~900 nm, NIR-Ⅰ) 相比, 其波长更长, 穿透深度更深, 自荧光更小, 因此设计合成在NIR-Ⅱ区具有较强吸收能力的纳米制剂具有更为重大的意义。Du等[8]构建了一种在NIR-Ⅱ区强吸收的Cu3BiSe3纳米颗粒, 具有增敏放疗的效果, 体内和体外实验结果均表明, 使用这一多模成像引导下的协同治疗纳米平台, 可以有效地杀死癌细胞, 抑制肿瘤的转移。
近年来, 单元素纳米生物制剂由于其组成单一、代谢机制易于分析等特点, 引起了生物医药领域的高度关注。Lei等[9]制备了直径约为2.7 nm超小尺寸的铋纳米点, 该纳米点在体内、体外实验中均展现了优异的肿瘤消融效果。治疗24 h后, 纳米点在肝脏的分布减少, 而在肿瘤的分布增加。收集24 h的小鼠粪便样品, 通过透射电镜观测可见形态完整的纳米点, 说明该材料在生理环境中具有优异的稳定性, 也进一步验证了纳米点被肝脏通过胆汁经粪便排出体外的结论[10]
Wang等[11]分别考察了明胶、牛血清蛋白和人血清蛋白修饰的铋纳米球的体内毒性、成像、酸度或近红外光响应能力、载药释药能力等方面的性能。研究结果证实明胶修饰的铋纳米球各种性能最佳, 并且外壳明胶在肿瘤微环境的微酸性介质中可降解, 更容易排出体外, 降低了体内残留风险。
含铋复合纳米材料具有极大的设计空间, 功能组合性能可以得到强化。因此, 合理地设计和构筑含铋复合纳米材料, 保持各复合组分的优势和功能, 调动各组分之间的协同作用, 可以最终实现“1加1大于2”的治疗效果, 展现更广阔的应用前景和空间。
由于肿瘤微环境的缺氧性质, 降低了肿瘤细胞对X射线辐射的敏感度, 影响放疗效果[12]。因此, 结合在肿瘤部位能够原位产氧的材料, 与铋基纳米材料组装成复合纳米诊疗平台, 是行之有效的途径。纳米酶是有效改善肿瘤乏氧微环境的不二选择。Liu等[13]构建了MnO2包覆Bi的核壳结构纳米颗粒, MnO2外壳与H2O2反应释放O2和•OH, 从而缓解缺氧并进行化学动力学治疗。更有趣的是, 肿瘤部位过表达的谷胱甘肽中去质子化硫醇基团会与Bi3+配位, 形成水溶性配合物, 有助于体内降解和排出。血液样本生化分析表明, 该材料对小鼠肝肾功能无影响, 溶血率小于5%, 说明其血液相容性良好。Zhao等[14]将Fe3O4和Bi2S3结合, 借助Bi2S3释放的热能, 刺激Fe3+/Fe2+的转换, 增强酶活性, 提高原位•OH的产量, 在光热成像和光声成像辅助下完成肿瘤治疗。近年来, 构建异质结构的复合纳米材料也是研究热点之一。Wang等[15]制备了基于Bi2Se3/MoSe2/Bi2Se3的层状夹心异质结构, 异质结构有效地降低了带隙(1.17 eV), 使光热转换效率提高到59.3%。Zhao等[16-19]选择Au纳米颗粒与Bi2S3或Bi2Se3构建异质结构, 实现多种ROS的原位释放, 取得了良好的抗肿瘤治疗效果。
尽管新颖的光敏化的铋基纳米材料被不断的开发, 但对它们的认识还相当有限: ①铋基纳米材料要发挥光疗效果需使用的光源强度过高, 治疗的安全性无法保障; ②缺乏明确的生物安全标准; ③体内清除途径的影响因素不明确且药代动力学层次的探究不够深入。
然而, 挑战即是机遇, 今后关于铋基纳米材料研究工作可深入探索以下两个方面: 一是寻找降低激发光源强度的突破口, 降低光毒性, 提高生物安全性; 二是深入探索体内清除途径、药代动力学层次等, 推动其在生物医学领域的发展。相信不久的将来铋基纳米材料可以在肿瘤临床诊疗中发挥重要的作用。
作者贡献: 王英杰负责起草并撰写文章; 高平和孙萌负责总结和归纳文献; 李磊姣负责论文选题、指导、审阅文章。
利益冲突: 所有作者均声明不存在利益冲突。
  • 国家自然基金面上项目(21871246)
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2023年第58卷第4期
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doi: 10.16438/j.0513-4870.2022-1089
  • 接收时间:2022-10-04
  • 首发时间:2025-11-21
  • 出版时间:2023-04-12
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  • 收稿日期:2022-10-04
  • 修回日期:2023-02-07
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国家自然基金面上项目(21871246)
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    长春理工大学化学与环境工程学院, 吉林 长春 130022

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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