Reversible Control over the Valency of a Nanoparticle-Based Supramolecular System

The reversible “catch-and-release” of small molecules from the surface of monolayer-protected gold nanoparticles is described. The valency of the system (i.e., the number of molecules bound to the surface) can be controlled through the addition and removal of metal ions from the monolayer. Both the change in valency and the release rate of the molecules are strongly pH-dependent. The release rate can be regulated by altering the ratio of metal ions in the monolayer

Controlling Supramolecular Complex Formation on the Surface of a Monolayer-Protected Gold Nanoparticle in Water

A combination of hydrophobic and electrostatic interactions drives the self-assembly of a large number of small molecules on the surface of a monolayer-protected gold nanoparticle. The hydrophobic interactions originate from the insertion of an aromatic unit in the hydrophobic part of the monolayer. This is evidenced by a shift in the emission wavelength of the fluorogenic probe upon binding. Up to around 35 small molecules can be simultaneously bound to the monolayer surface at micromolar concentrations in water. It is shown that an understanding of the supramolecular interactions that drive complex formation on the monolayer surface provides unprecedented control over the supramolecular chemistry occurring on the surface. By taking advantage of the different kinds of noncovalent interactions present in different probes, it is possibile to displace one type of surface-bound molecule from a heteromeric surface selectively. Finally, it is also possible to catch and release one type of surface-bound molecule selectively

A Polymer Prodrug Strategy to Switch from Intravenous to Subcutaneous Cancer Therapy for Irritant/Vesicant Drugs

Chemotherapy is almost exclusively administered via the intravenous (IV) route, which has serious limitations (e.g., patient discomfort, long hospital stays, need for trained staff, high cost, catheter failures, infections). Therefore, the development of effective and less costly chemotherapy that is more comfortable for the patient would revolutionize cancer therapy. While subcutaneous (SC) administration has the potential to meet these criteria, it is extremely restrictive as it cannot be applied to most anticancer drugs, such as irritant or vesicant ones, for local toxicity reasons. Herein, we report a facile, general, and scalable approach for the SC administration of anticancer drugs through the design of well-defined hydrophilic polymer prodrugs. This was applied to the anticancer drug paclitaxel (Ptx) as a worst-case scenario due to its high hydrophobicity and vesicant properties (two factors promoting necrosis at the injection site). After a preliminary screening of well-established polymers used in nanomedicine, polyacrylamide (PAAm) was chosen as a hydrophilic polymer owing to its greater physicochemical, pharmacokinetic, and tumor accumulation properties. A small library of Ptx-based polymer prodrugs was designed by adjusting the nature of the linker (ester, diglycolate, and carbonate) and then evaluated in terms of rheological/viscosity properties in aqueous solutions, drug release kinetics in PBS and in murine plasma, cytotoxicity on two different cancer cell lines, acute local and systemic toxicity, pharmacokinetics and biodistribution, and finally their anticancer efficacy. We demonstrated that Ptx-PAAm polymer prodrugs could be safely injected subcutaneously without inducing local toxicity while outperforming Taxol, the commercial formulation of Ptx, thus opening the door to the safe transposition from IV to SC chemotherapy

Stable π‑Extended Thio[7]helicene-Based Diradical with Predominant Through-Space Spin–Spin Coupling

In this work, a novel π-extended thio[7]helicene scaffold was synthesized, where the α-position of the thiophene unit could be functionalized with bulky phenoxy radicals after considerable synthetic attempts. This open-shell helical diradical, ET7H-R, possesses high stability in the air, nontrivial π conjugation, persistent chirality, and a high diradical character (y0 of 0.998). The key feature is a predominant through-space spin–spin coupling (TSC) between two radicals at the helical terminals. Variable-temperature continuous-wave electron spin resonance (cw-ESR) and superconducting quantum interference device (SQUID) magnetometry in the solid state reveal a singlet ground state with a nearly degenerate triplet state of ET7H-R. These results highlight the significance of a stable helical diradicaloid as a promising platform for investigating intramolecular TSCs