Experimental and Computational Investigation of Clustering Behavior of Cyclodextrin-Perfluorocarbon Inclusion Complexes as Effective Histotripsy Agents.
Experimental and Computational Investigation of Clustering Behavior of Cyclodextrin-Perfluorocarbon Inclusion Complexes as Effective Histotripsy Agents.
复制标题
环糊精-全氟化碳包合物作为有效组织解剖剂的聚类行为的实验和计算研究。
DOI：
10.1021/acs.molpharmaceut.2c00268
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发表时间：
2022
影响因子：
4.9
通讯作者：
YukselDurmaz,Yasemin
中科院分区：
文献类型：
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作者：
Kaymaz,Betül;Mustafa,Waleed;Hall,Sarah;Vlaisavljevich,Eli;Sensoy,Ozge;YukselDurmaz,Yasemin
最近开发的纳米锥（NC）是由环糊精（CD）和全氟化碳（PFC）组成的包合复合物，由于稳定的包合复合、PFC定量、简单的合成和加工，在纳米颗粒介导的组织破坏（NMH）应用中显示出有希望的结果。FDA批准的βCD及其修饰形式（如低度甲基化βCD）先前已被证明是能够容纳PFC分子的结构的主要例子。然而，在PFC分子存在下，具有各种空腔大小的不同CD的复合物形成潜力及其随后的聚集，需要探索。在本研究中，一些天然CD及其各自的衍生物暴露于全氟戊烷（PFP）和全氟己烷（PFH）的络合和聚集的潜力进行了研究，在湿实验室。还进行了计算研究，以说明由于CD复合物中PFC的光密度较低而导致PFC定量面临的局限性，并发现NMH应用的最佳候选者。所有结果表明，只有βCD和γCD（HMγCD除外）衍生物与PFCs形成包合物，只有LMβCD、βCD和γCD形成纳米锥簇（NCC），这些NCC沉淀并可收集使用。此外，数据共同表明，βCD和PFC具有最好的络合作用，这是由于稳定的络合物形成、易于生产和产物回收，特别是PFH作为更合适的候选物，这是由于其高沸点，这允许在合成期间的可加工性。虽然模拟表明存在高度稳定的包合物，如HPβCD，但由于CD在水中的高溶解度，导致沉淀的簇形成受到阻碍，即使在采用一般实验室回收方法后，也会产生无形的产量。最后，组织破坏空化实验成功地显示出在所鉴定的最佳NCC候选者中降低的空化阈值，支持它们在NMH中的使用。
Recently developed nanocones (NCs), which are inclusion complexes that are made up of cyclodextrins (CDs) and perfluorocarbons (PFCs), have shown promising results in nanoparticle-mediated histotripsy (NMH) applications due to stable inclusion complexation, PFC quantification, simple synthesis, and processing. FDA-approved βCD and its modified versions such as low-degree methylated βCD have been previously demonstrated as prime examples of structures capable of accommodating PFC molecules. However, the complex formation potential of different CDs with various cavity sizes in the presence of PFC molecules, and their consequent aggregation, needs to be explored. In the present study, the complexation and aggregation potential of some natural CDs and their respective derivatives either exposed to perfluoropentane (PFP) or perfluorohexane (PFH) were studied in the wet lab. Computational studies were also performed to account for the limitations faced in PFC quantification because of the low optical density of PFCs within the CD complex and to discover the best candidate for NMH applications. All results revealed that only βCD and γCD (except HMγCD) derivatives form an inclusion complex with PFCs and only LMβCD, βCD, and γCD form nanocone clusters (NCCs), which precipitate and can be collected for use. Furthermore, the data collectively show that βCD and PFCs have the best complexation due to stable complex formation, ease of production, and product recovery, especially with PFH as a more suitable candidate due to its high boiling point, which allows workability during synthesis. Although simulations suggest that highly stable inclusion complexes exist, such as HPβCD, the cluster formation resulting in precipitation is hindered due to the high solubility of CDs in water, resulting in intangible yields to work with even after employing general laboratory recovery methods. Conclusively, histotripsy cavitation experiments successfully showed a decreased cavitation threshold among optimal NCC candidates that were identified, supporting their use in NMH.