Self-Assembly of a Triazolylferrocenyl Dendrimer in Water Yields Nontraditional Intrinsic Green Fluorescent Vesosomes for Nanotheranostic Applications

Abstract

The promising field of nanomedicine stimulates a continuous search for multifunctional nanotheranostic systems for imaging and drug delivery. Herein, we demonstrate that application of supramolecular chemistry’s concepts in dendritic assemblies can enable the formation of advanced dendrimer-based nanotheranostic devices. A dendrimer bearing 81 triazolylferrocenyl terminal groups adopts a more compact shell-like structure in polar solvents with the ferrocenyl peripheral groups backfolding toward the hydrophobic dendrimer interior, while exposing the more polar triazole moieties as the dendritic shell. Akin to lipids, the compact dendritic structure self-assembles into uniform nanovesicles that in turn self-assemble into larger vesosomes in water. The vesosomes emit green nontraditional intrinsic fluorescence (NTIL), which is an emerging property as there are no classical fluorophores in the dendritic macromolecular structure. This work confirms the hypothesis that the NTIL emission is greatly enhanced by rigidification of the supramolecular assemblies containing heteroatomic subluminophores (HASLs) and by the presence of electron rich functional groups on the periphery of dendrimers. This work is the first one detecting NTIL in ferrocenyl-terminated dendrimers. Moreover, the vesosomes are stable in biological medium, are uptaken by cells, and show cytotoxic activity against cancer cells. Accordingly, the self-organization of these dendrimers into tertiary structures promotes the emergence of new properties enabling the same component, in this case, ferrocenyl group, to function as both antitumoral drug and fluorophore.

Water‐Soluble Well‐Defined Bifunctional Ferrocenyl Dendrimer with Anti‐Cancer Activity

“…Our group has reported a series of folate derivatives containing ferrocenyl groups and it was found that the folate bearing a triazole group conjugated to the ferrocenyl unit was the most active compound against cancer cells, being the lowest IC 50 value obtained against MCF‐7 cells (21.7 μM) [11] . Moreover, the cytotoxicity of self‐assembled structures of a dendrimer bearing eighty one triazolylferrocenyl groups with nontraditional intrinsic fluorescence was also evaluated [13] . These assemblies were able to penetrate the intracellular medium of MCF‐7 cells, changing cells′ morphology, and exhibiting IC 50 of 124 μM of Fc groups or 1.5 μM of dendrimer after 48 h of treatment.…”

“…Conjugation of ferrocenyl units to dendrimers have resulted in redox‐active macromolecular systems with interesting properties to many fields of science [12] . Recently, we have reported that a hydrophobic dendrimer bearing 81 triazolylferrocenyl termini self‐assembled into large vesosomes in aqueous medium [13] . These vesosomes emit green nontraditional intrinsic fluorescence (NTIL) and present activity against cancer cells [13] …”

“…Recently, we have reported that a hydrophobic dendrimer bearing 81 triazolylferrocenyl termini self‐assembled into large vesosomes in aqueous medium [13] . These vesosomes emit green nontraditional intrinsic fluorescence (NTIL) and present activity against cancer cells [13] …”

“…[12] Recently, we have reported that a hydrophobic dendrimer bearing 81 triazolylferrocenyl termini self-assembled into large vesosomes in aqueous medium. [13] These vesosomes emit green nontraditional intrinsic fluorescence (NTIL) and present activity against cancer cells. [13] Herein we demonstrate the synthesis and characterization of a 1!3 branched polyamide well-defined bifunctional dendrimer bearing 18 triazolylferrocenyl and 18 carboxylic acid termini.…”

Fabrication of CaCO3-Coated Vesicles by Biomineralization and Their Application as Carriers of Drug Delivery Systems

“…DDS is a system that delivers the drugs “in a minimum amount”, “at the right time”, and “to the right place”. Polymer micelles [ 5 , 6 ], dendrimers [ 7 , 8 , 9 ], hydrogels [ 10 , 11 , 12 , 13 ], and mesoporous nanoparticles [ 14 , 15 , 16 ] have been reported as DDS carriers. In addition, vesicles have been used for DDS carriers.…”