Experimental and Computational Characterization of the Interaction between Gold Nanoparticles and Polyamidoamine Dendrimers.

Dendrimers provide a means to control the synthesis of gold nanoparticles and stabilize their suspensions. However, design of improved dendrimers for this application is hindered by a lack of understanding how the dendrimers and synthesis conditions determine nanoparticle morphology and suspension stability. In the present work, we evaluate the effect of polyamidoamine (PAMAM) dendrimers terminated with different functional groups (-OH or -NH3+) and different synthesis conditions on the morphology of the resulting gold nanoparticles and their stability in solution. We leverage molecular dynamics (MD) simulations to identify the atomic interactions that underlie adsorption of PAMAM dendrimers to gold surface and how the thermodynamics of this adsorption depends on the terminal functional groups of the dendrimers. We find that gold nanoparticles formed with hydroxyl-terminated PAMAM (PAMAM-OH) rapidly aggregate, whereas those formed with PAMAM-NH3+ are stable in solution for months of storage. Synthesis under ultrasound sonication is shown to be more rapid than that under agitation, with sonication producing smaller nanoparticles. Free-energy calculations in MD simulations show that all dendrimers have a high affinity for the gold surface, although PAMAM-OH and its oxidized aldehyde form (PAMAM-CHO) have a greater affinity for the nanoparticle surface than PAMAM-NH3+. Although adsorption of PAMAM-OH and PAMAM-CHO has both favorable entropy and enthalpy, adsorption of PAMAM-NH3+ is driven by a strong enthalpic component subject to an unfavorable entropic component.

Mechanistic Studies on the Self-Assembly of PLGA Patchy Particles and Their Potential Applications in Biomedical Imaging.

Currently, several challenges prevent poly(lactic-co-glycolic acid) (PLGA) particles from reaching clinical settings. Among these is a lack of understanding of the molecular mechanisms involved in the formation of these particles. We have been studying in depth the formation of patchy polymeric particles. These particles are made of PLGA and lipid-polymer functional groups. They have unique patch-core-shell structural features: hollow or solid hydrophobic cores and a patchy surface. Previously, we identified the shear stress as the most important parameter in a patchy particle's formation. Here, we investigated in detail the role of shear stress in the patchy particle's internal and external structure using an integrative experimental and computational approach. By cross-sectioning the multipatch particles, we found lipid-based structures embedded in the entire PLGA matrix, which represents a unique finding in the PLGA field. By developing novel computational fluid dynamics and molecular dynamics simulations, we found that the shear stress determines the internal structure of the patchy particles. Equally important, we discovered that these particles emit a photoacoustic (PA) signal in the optical clinical imaging window. Our results show that particles with multiple patches emit a higher PA signal than single-patch particles. This phenomenon most likely is due to the fact that multipatchy particles absorb more heat than single-patchy particles as shown by differential scanning calorimetry analysis. Furthermore, we demonstrated the use of patchy polymeric particles as photoacoustic molecular probes both in vitro and in vivo studies. The fundamental studies described here will help us to design more effective PLGA carriers for a number of medical applications as well as to accelerate their medical translation.

PAMAM G4 dendrimers as inhibitors of the iron storage properties of human L-chain ferritin.

Cationic dendrimers, such as PAMAM, are known to be positively charged at neutral pH allowing their unspecific interaction with proteins and other cellular components. Especially, ferritin, which has an important role in iron homeostasis, presents a negative electrostatic potential at the 3-fold channel. This channel is important in the functionality of ferritin because it allows the iron entry into its inner cavity. In this way, the interaction between the protonated terminal amines of the dendrimer and the negatively charged 3-fold channels of ferritin is expected. Experimental measurements demonstrated that PAMAM G4 inhibits the iron storage properties of L-chain human ferritin (L-Ftn). Molecular dynamics simulations have been used to analyze the specific interaction between PAMAM G4 and L-Ftn. Results show that PAMAM G4 effectively interacts with the 3-fold channels of L-Ftn, suggesting that this interaction is responsible for the inhibition of the iron storage properties of L-Ftn.