Amphiphilic p-Sulfonatocalix[4]arene as “Drug Chaperone” for Escorting Anticancer Drugs

Abstract

Supramolecularly constructing multifunctional platform for drug delivery is a challenging task. In this work, we propose a novel supramolecular strategy “drug chaperone”, in which macrocyclic amphiphiles directly coassemble with cationic drugs into a multifunctional platform and its surface is further decorated with targeting ligands through host–guest recognition. The coassembling and hierarchical decoration processes were monitored by optical transmittance measurements, and the size and morphology of amphiphilic coassemblies were identified by dynamic light scattering and high-resolution transmission electron microscopy. In cell experiments to validate the drug chaperone strategy, the anticancer activities of free drugs were pronouncedly improved by coassembling with amphiphilic chaperone and further functionalization with targeting ligand.

Encapsulation of Temozolomide in a Calixarene Nanocapsule Improves Its Stability and Enhances Its Therapeutic Efficacy against Glioblastoma

“…There are several other approaches that could be taken to further enhance the antitumor efficacy of the TMZ@Calix complex. For example, coassembly of amphiphilic p-sulphonatocalix [4]arenes into multifunctional drug carriers that can be functionalized by decorating them with tumor targeting ligands have been explored in recent years, and this approach could also be used to deliver TMZ (41,42). The TMZ@Calix complex could also be functionalized with a potent MGMT inhibitor to further enhance its efficacy against MGMT-expressing TMZ-resistant tumors (43).…”

Orthogonal self-assembly of an organoplatinum(II) metallacycle and cucurbit[8]uril that delivers curcumin to cancer cells

“…Various nanocarriers including nanostructures (28)(29)(30)(31), conjugates (32)(33)(34), hydrogels (35), carbon nanomaterials (36), and so on have been developed to overcome this problem. Likewise, the solubility, stability, and bioavailability of anticancer drugs have been significantly improved in physiological environments via host-guest complexations (37)(38)(39)(40). Lippard and coworkers (41) reported a hexanuclear Pt(II) cage as a drug delivery vehicle to deliver a Pt(II) prodrug to cancer cells.…”

Host-Guest Chemistry in Supramolecular Theranostics

“…Liu et al . used an amphiphilic p -sulfonatocalixarene as a “drug chaperone” to coassemble with cationic drugs (mitoxantrone∙HCl and irinotecan∙HCl) into a multifunctional platform driven by multivalent charge interactions (Figure 8a) 143. The loaded drugs were protected by the amphiphilic drug chaperone premature degradation upon formation of nanostructures.…”

“…(a) Functionalization protocol of the “drug chaperone” strategy and chemical structures of anticancer drugs, SC4AH and targeting ligands. Reproduced with permission from 143, copyright 2015 Nature Publishing Group. (b) Molecular structure of the building blocks and schematic illustration of the construction of a supramolecular binary vesicle via complexation of calix[4]arene (C4AS) with MVC 12 .…”