On the encapsulation and assembly of anticancer drugs in a cooperative fashion† †Electronic supplementary information (ESI) available: The preparation and characterization of 1 with additional experimental and computational details. See DOI: 10.1039/c9sc01380f

Autor: Wang, Weikun, Wang, Han, Zhiquan, Lei, Xie, Han, Cui, Honggang, Badjić, Jovica D.
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Chemical Science
ISSN: 2041-6539
2041-6520
Popis: In this study, we report the remarkable recognition and assembly characteristics of D3h symmetric basket 16– containing two adjoining and nonpolar cavities with six biocompatible GABA residues at their northern and southern termini.
In this study, we report the remarkable recognition and assembly characteristics of D3h symmetric basket 16– containing two adjoining and nonpolar cavities with six biocompatible GABA residues at their northern and southern termini. From the results of experimental (1H NMR, fluorescence and UV-Vis spectroscopies) and computational (MM-MC/OPLS3e) investigations, we deduced that hexaanionic 16– captured two molecules of anticancer drug doxorubicin 2+ in water and accommodated them in its two deep cavities. The formation of stable 16–⊂222+ (Ka = 3 × 1012 M–2) was accompanied by the exceptional homotopic cooperativity (α = 4K2/K1 = 112) in which K1 = 3.2 ± 0.8 × 105 M–1 and K2 = 9 ± 1 × 106 M–1. Furthermore, bolaamphiphilic 16–⊂222+ assembled into spherical nanoparticles (DLS, cryo-TEM and TEM) possessing 41% drug loading. The preorganization of abiotic receptor 16– and its complementarity to 2+ have been proposed to play a part in the positive cooperativity in which ten favorable noncovalent contacts (i.e. hydrogen bonds, salt bridges, C–H···π and π–π contacts) are formed between doxorubicin and the dual-cavity host. In the case of topotecan 3+, however, the absence of multiple and favorable basket⊂drug interactions resulted in the predominant formation of a binary 16– ⊂ 3+ complex (K1 = 2.12 ± 0.01 × 104 M–1) and the negative homotopic allostery (α ≪ 1). To summarize, our study lays out a roadmap for creating a family of novel, accessible and multivalent hosts capable of complexing anticancer agents in a cooperative manner. As basket⊂drug complexes organize into highly loaded nanoparticles, the reported soft material is amenable to the bottom-up construction of stimuli-responsive nanomedicine capable of effective scavenging and/or delivery of drugs.
Databáze: OpenAIRE
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