Issue 22, 2022

Aqueous synthesis and self-assembly of bioactive and thermo-responsive HA-b-ELP bioconjugates

Abstract

The design of synthetic (bio)macromolecules that combine biocompatibility, self-assembly and bioactivity properties at the molecular level is an intense field of research for biomedical applications such as (nano)medicine. In this contribution, we have designed and synthesized a library of bioactive and thermo-responsive bioconjugates from elastin-like polypeptides (ELPs) and hyaluronic acid (HA) in order to access bioactive self-assembled nanoparticles. These were prepared by a simple synthetic and purification strategy, compatible with the requirements for biological applications and industrial scale-up. A series of 9 HA-b-ELP bioconjugates with different compositions and block lengths was synthesized under aqueous conditions by strain-promoted azide–alkyne cycloaddition (SPAAC), avoiding the use of catalysts, co-reactants and organic solvents, and isolated by a simple centrifugation step. An extensive physico-chemical study was then performed on the whole library of bioconjugates in an attempt to establish structure–property relationships. In particular, the determination of the critical conditions for thermally driven self-assembly was carried out upon temperature (CMT) and concentration (CMC) gradients, leading to a phase diagram for each of these bioconjugates. These parameters and the size of nanoparticles were found to depend on the chemical composition of the bioconjugates, namely on the respective size of individual blocks. Understanding the mechanism underlying this dependency is a real asset for designing more effective experiments: with key criteria defined (e.g. concentration, temperature, salinity, and biological target), the composition of the best candidates can be rationalized. In particular, four of the bioconjugates (HA4.6k-ELPn80 or n100 and HA24k-ELPn80 or n100) were found to self-assemble into well-defined spherical core–shell nanoparticles, with a negative surface charge due to the HA block exposed at the surface, a hydrodynamic diameter between 40 and 200 nm under physiological conditions and a good stability over time at 37 °C. We therefore propose here a versatile and simple design of smart, controllable, and bioactive nanoparticles that present different behaviors depending on the diblocks’ composition.

Graphical abstract: Aqueous synthesis and self-assembly of bioactive and thermo-responsive HA-b-ELP bioconjugates

Supplementary files

Article information

Article type
Paper
Submitted
21 7 2022
Accepted
12 9 2022
First published
13 9 2022

Biomater. Sci., 2022,10, 6365-6376

Aqueous synthesis and self-assembly of bioactive and thermo-responsive HA-b-ELP bioconjugates

M. Levêque, Y. Xiao, L. Durand, L. Massé, E. Garanger and S. Lecommandoux, Biomater. Sci., 2022, 10, 6365 DOI: 10.1039/D2BM01149B

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