Molecular Ballet: Investigating the Complex Interaction between Self-Assembling Dendrimers and Human Serum Albumin via Computational and Experimental Methods.

Dendrimers, intricate macromolecules with highly branched nanostructures, offer unique attributes including precise control over size, shape, and functionality, making them promising candidates for a wide range of biomedical applications. The exploration of their interaction with biological environments, particularly human serum albumin (HSA), holds significant importance for biomedical utilization. In this study, the interaction between HSA and a recently developed self-assembling amphiphilic dendrimer (AD) was investigated using various experimental techniques. Fluorescence spectroscopy and isothermal titration calorimetry revealed moderate interactions between the protein and the AD nanomicelles (NMs), primarily attributed to favorable enthalpic contributions arising from electrostatic interactions and hydrogen bonding. Structural analysis indicated minimal changes in HSA upon complexation with the AD NMs, which was further supported by computational simulations demonstrating stable interactions at the atomistic level. These findings provide valuable insights into the binding mechanisms and thermodynamic parameters governing HSA/AD NM interactions, thereby contributing to the understanding of their potential biomedical applications.

Some things old, new and borrowed: Delivery of dabrafenib and vemurafenib to melanoma cells via self-assembled nanomicelles based on an amphiphilic dendrimer.

Two clinically approved anticancer drugs targeting BRAF in melanoma patients - dabrafenib (DAB) and vemurafenib (VEM) - have been successfully encapsulated into nanomicelles formed upon self-assembly of an amphiphilic dendrimer AD based on two C18 aliphatic chains and a G2 PAMAM head. The process resulted in the formation of well-defined (∼10 nm) core-shell nanomicelles (NMs) with excellent encapsulation efficiency (∼70% for DAB and ∼60% for VEM) and good drug loading capacity (∼27% and ∼24% for DAB and VEM, respectively). Dynamic light scattering (DLS), transmission electron microscopy (TEM), small-angle x-ray scattering (SAXS), nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC), and molecular simulation (MS) experiments were used, respectively, to determine the size and structure of the empty and drug-loaded nanomicelles (DLNMs), along with the interactions between the NMs and their cargoes. The in vitro release data revealed profiles governed by Fickian diffusion; moreover, for both anticancer molecules, an acidic environment (pH = 5.0) facilitated drug release with respect to physiological pH conditions (pH = 7.4). Finally, both DAB- and VEM-loaded NMs elicited enhanced response with respect to free drug treatments in 4 different melanoma cell lines.