Side-by-side comparison of dendritic-linear hybrids and their hyperbranched analogs as micellar carriers of chemotherapeutics

Abstract

Amphiphilic block copolymers are successfully synthesized possessing a hydrophobic dendritic component based on the bis‐MPA monomer and a hydrophilic linear polyethylene glycol (PEG) component. The hybrids were either conjured in small scale using robust click reactions between perfect dendrons and linear PEG or multigram polycondensation of hyperbranched blocks from PEG. In all cases, the amphiphiles were assembled to micelles, were found nontoxic and successfully loaded with the chemotherapeutic doxorubicin.

Supramolecular anticancer drug delivery systems based on linear–dendritic copolymers

“…94 Also a reduced cell viability of 55% has been determined for DOX-PEG-(G4)-(Bz) 8 (Compound 13) containing 10 µg ml −1 DOX, in comparison with 73% cell viability obtained at the same concentration of free DOX, showing that DOX-loaded micelles delivered the therapeutic effect with high efficacy. 129 In summary, DOX encapsulated PEG-block-bis-MPA polyesters (G4)-(Bz) 8 showed some advantages, such as nontoxicity of the linear-dendritic carrier and the higher cytotoxic effect against MDA-MB-231 cancer cells in comparison with free DOX. However, higher molecular weights of PEG are necessary to provide sufficient stealth or steric repulsion during DOX loading and to avoid aggregation.…”

“…32 Using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC)-based click chemistry and "dendrone-first" method, Hed et al synthesized a set of dendritic linear hybrid materials composed of linear PEG and dendritic aliphatic bis-MPA polyesters (G4). 129 To achieve amphiphilic structures, the bis-MPA layer also introduced hydrophobicity, using benzylidene-protected bis-MPA anhydride. Finally, the convergent coupling was carried out between monofunctional PEG5k-acetylene and azide functional dendrons azide-[G4]-(Bz) 8 by CuAAC click chemistry (Fig.…”

“…Pharmacokinetics studies and in vivo tests can help this system develop for cancer therapy. 129 By flow cytometry profiles it has been proved that the DOXloaded PEO5K-PAMAM (D3)-diazonaphthoquinone (DNQ) micelles (Compound 14) could quickly enter into HeLa cells in a time-independent manner compared with free DOX (Fig. 24).…”

Synthesis and tunable thermoresponsive solution morphologies of 2,2‐bis‐methylolpropionic acid dendron–azobenzene–poly(N‐isopropyl acrylamide) copolymers

“…Nano‐assemblies of stimuli‐responsive amphiphilic polymers have attracted attention for applications in biomedicine, sensors and nanoreactors owing to their ability to undergo change in morphology or disassembly in response to stimuli . Since the morphological transformation also alters the encapsulation and release behaviour of an assembly, this property is particularly important for drug delivery applications where it can be exploited to achieve controlled release of an encapsulated drug in the environment of cancer cells that show higher temperature and lower pH compared to healthy cells . Amphiphilic block copolymers containing one or more moieties responsive to various stimuli such as pH, temperature, light, CO 2 and reducing environment have been extensively studied in this direction .…”

Effect of the Branching Pattern of Hydrophobic Dendrons on the Core Structure of Linear‐Dendritic Copolymer Micelles

“…Amphiphilic linear‐dendritic copolymers have emerged as promising candidates for controlled generation of supramolecular aggregates in solution . These assemblies are interesting for various applications including drug delivery . This interest stems from the fact that these anisotropic polymers combine useful features from the constituent blocks – the perfectly branched structure and encapsulation ability of dendrons, and chain entanglement of linear polymers.…”