Dynamic nanosurface reconfiguration by host-guest supramolecular interactions.

The dynamic functionalization of the nanoparticle surface with biocompatible coatings is a critical step towards the development of functional nano-sized systems. While covalent approaches have been broadly exploited in the stabilization of nanoparticle colloidal systems, these strategies hinder the dynamic nanosurface chemical reconfiguration. Supramolecular strategies based on specific host-guest interactions hold promise due to their intrinsic reversibility, self-healing capabilities and modularity. Host/guest couples have recently been implemented in nanoparticle platforms for the exchange and release of effector molecules. However, the direct exchange of biocompatible hydrophilic oligomers (e.g. peptides) for the modulation of the surface charge and chemical properties of nanoparticles still remains a challenge. Here, we show the intracellular reconfiguration of nanoparticles by a host/guest mechanism with biocompatible oligomeric competitors. The surface of gold nanoparticles was functionalized with cyclodextrin hosts and the guest exchange was studied with biocompatible mono and divalent adamantyl competitors. The systematic characterization of the size and surface potential of the host/guest nanoparticles allowed the optimization of the binding and the stabilization properties of these supramolecular systems. The in cellulo host/guest-mediated direct reconfiguration of the peptide layer at the surface of nanoparticles is achieved by controlling the valence of adamantane-equipped peptides. This work demonstrates that host/guest supramolecular systems can be exploited for the direct exchange of pendants at the surface of nanoparticles and the intracellular dynamic chemical reconfiguration of biocompatible colloidal systems.

UV-responsive cyclic peptide progelator bioinks.

We describe cyclic peptide progelators which cleave in response to UV light to generate linearized peptides which then self-assemble into gel networks. Cyclic peptide progelators were synthesized, where the peptides were sterically constrained, but upon UV irradiation, predictable cleavage products were generated. Amino acid sequences and formulation conditions were altered to tune the mechanical properties of the resulting gels. Characterization of the resulting morphologies and chemistry was achieved through liquid phase and standard TEM methods, combined with matrix assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS).

Supramolecular caging for cytosolic delivery of anionic probes.

The cytosolic delivery of hydrophilic, anionic molecular probes and therapeutics is a major challenge in chemical biology and medicine. Herein, we describe the design and synthesis of peptide-cage hybrids that allow an efficient supramolecular binding, cell membrane translocation and cytosolic delivery of a number of anionic dyes, including pyranine, carboxyfluorescein and several sulfonate-containing Alexa dyes. This supramolecular caging strategy is successful in different cell lines, and the dynamic carrier mechanism has been validated by U-tube experiments. The high efficiency of the reported approach allowed intracellular pH tracking by exploiting the ratiometric excitation of the pyranine fluorescent probe.