Evaluation of the stability of cucurbit[8]uril-based ternary host−guest complexation in physiological environment and the fabrication of a supramolecular theranostic nanomedicine

Journal of Nanobiotechnology

Dan Wu¹  Jiajun Ye²  Fei Kang²  Jie Shen³  Bing Bai⁴  Zuobing Chen⁴  Shaolong Qi⁵  Guocan Yu⁵  Han Wu⁵ 

[1] College of Materials Science and Engineering, Zhejiang University of Technology;Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University;Department of Pharmacy, School of Medicine, Zhejiang University City College;Department of Rehabilitation Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University;Key Laboratory of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University;

关键词: Supramolecular chemistry;    Host–guest molecular recognition;    Nanomedicine;    Drug delivery;    Chemotherapy;   

DOI  :  10.1186/s12951-021-01076-z

来源: DOAJ

【 摘 要 】

Abstract Background Supramolecular theranostics have exhibited promising potentials in disease diagnosis and therapy by taking advantages of the dynamic and reversible nature of non-covalent interactions. It is extremely important to figure out the stability of the driving forces in physiological environment for the preparation of theranostic systems. Methods The host−guest complexation between cucurbit[8]uril (CB[8]), 4,4′-bipyridinium, and napththyl guest was fully studied using various characterizations, including nuclear magnetic resonance spectroscopy, ultraviolet–visible (UV–vis) spectroscopy, isothermal titration calorimetry (ITC). The association constants of this ternary complex were determined using isothermal titration calorimetry. The stability of the non-covalent interactions and self-assemblies form from this molecular recognition was confirmed by UV–vis spectroscopy and dynamic light scattering (DLS). A supramolecular nanomedicine was constructed on the basis of this 1:1:1 ternary recognition, and its in vitro and in vivo anticancer efficacy were thoroughly evaluated. Positron emission tomography (PET) imaging was used to monitor the delivery and biodistribution of the supramolecular nanomedicine. Results Various experiments confirmed that the ternary complexation between 4,4′-bipyridinium, and napththyl derivative and CB[8] was stable in physiological environment, including phosphate buffered solution and cell culture medium. Supramolecular nanomedicine (SNM@DOX) encapsulating a neutral anticancer drug (doxrubincin, DOX) was prepared based on this molecular recognition that linked the hydrophobic poly(ε-caprolactone) chain and hydrophilic polyethylene glycol segment. The non-covalent interactions guaranteed the stability of SNM@DOX during blood circulation and promoted its tumor accumulation by taking advantage of the enhanced permeability and retention effect, thus greatly improving the anti-tumor efficacy as compared with the free drug. Conclusion Arising from the host-enhanced charge-transfer interactions, the CB[8]-based ternary recognition was stable enough in physiological environment, which was suitable for the fabrication of supramolecular nanotheranostics showing promising potentials in precise cancer diagnosis and therapy. Graphic Abstract

【 授权许可】

Unknown