Novel stable dendrimersome formulation for safe bioimaging applications

Abstract

a Dendrimersomes are nanosized vesicles constituted by amphiphilic Janus dendrimers (JDs), which have been recently proposed as innovative nanocarriers for biomedical applications. Recently, we have demonstrated that dendrimersomes self-assembled from (3,5)12G1-PE-BMPA-G2-(OH) 8 dendrimers can be successfully loaded with hydrophilic and amphiphilic imaging contrast agents. Here, we present two newly synthesized low generation isomeric JDs: JDG0G1(3,5) and JDG0G1(3,4). Though less branched than the above-cited dendrimers, they retain the ability to form self-assembled, almost monodisperse vesicular nanoparticles. This contribution reports on the characterization of such nanovesicles loaded with the clinically approved MRI probe Gadoteridol and the comparison with the related nanoparticles assembled from more branched dendrimers. Special emphasis was given to the in vitro stability test of the systems in biologically relevant media, complemented by preliminary in vivo data about blood circulation lifetime collected from healthy mice. The results point to very promising safety and stability profiles of the nanovesicles, in particular for those made of JDG0G1(3,5), whose spontaneous self-organization in water gives rise to a homogeneous suspension. Importantly, the blood lifetimes of these systems are comparable to those of standard liposomes. By virtue of the reported results, the herein presented nanovesicles augur well for future use in a variety of biomedical applications.

Multifunctional triazolylferrocenyl Janus dendron: Nanoparticle stabilizer, smart drug carrier and supramolecular nanoreactor

“…Amphiphilic Janus dendrimers and dendrons feature various well‐defined and complex self‐assembled structures such as micelles, vesicles, cubosomes, discs, tubular vesicles, helical ribbons and bilayered vesicles called dendrimersomes, and their potential applications for drug delivery . Redox‐responsive Fc‐containing macromolecules have recently gained considerable attention due to their potential in controllable delivery and release in physiological environments, where redox reactions are widely and constantly present .…”

“…Janus dendrimers (JDs) are newly emerging types of dendrimers and are normally constructed of two different dendrons with varying size and functionality to obtain a single amphiphilic or heterofunctional macromolecule . Their asymmetric structures lead to new and efficient characteristic properties for the formation of complex self‐assembled materials that are presently inconceivable for homogeneous or symmetric dendrimers, and many applications have been investigated, especially in the fields of materials and biology, such as thermal actuators, ionic liquids, catalysis, light harvesting systems, bioimaging, optoelectronics and drug delivery …”

Dendrimersomes Exhibit Lamellar-to-Sponge Phase Transitions

“…23–31 Changes in the permeability of DMSs can also be assessed relaxometrically. 32,33 DMS heterogeneity in our preparations, in terms of both structure and size, required fluorescently labeled JDs to characterize the lamellar-to-sponge transition using fluorescence polarization, FRAP, and permeability experiments rather than spectroscopic techniques which rely on sample homogeneity. Using these techniques along with cryo-TEM, we demonstrate that the lamellar-to-sponge transition occurs not only for dumbbell-like DMSs of mixed JD composition but also for single-component DMSs made of R H only or R F only.…”

GdDOTAGA(C18)2: an efficient amphiphilic Gd(iii) chelate for the preparation of self-assembled high relaxivity MRI nanoprobes

“…1,2 The versatility of nanosystems allows tuneable surface modification and loading with different chemicals (drugs, imaging agents, targeting vectors) with the aim of fine-optimizing the biological properties of the nanocarriers, while simultaneously enabling them to perform diagnostically and/or therapeutically important functions. 3,4 Lipid-containing nanoparticles (LNPs), 5 like micelles, liposomes, and solid lipid nanoparticles, or other similar nanosystems (such as the recently developed dendrimersomes) [6][7][8] are based on supramolecular aggregates obtained by spontaneous assembling in aqueous solution of phospholipids alone or in mixture with other amphiphilic molecules. Such objects have been frequently used as nanocarriers for drug delivery and imaging applications due to their great chemical versatility that allows the loading of hydrophobic, amphiphilic, and hydrophilic substances, and surface decoration with targeting vectors, blood lifetime modulators, and diagnostic agents.…”