High-Resolution Imaging of Polyethylene Glycol Coated Dendrimers via Combined Atomic Force and Scanning Tunneling Microscopy

Abstract

Dendrimers have shown great promise as drug delivery vehicles in recent years because they can be synthesized with designed size and functionalities for optimal transportation, targeting, and biocompatibility. One of the most well-known termini used for biocompatibility is polyethylene glycol (PEG), whose performance is affected by its actual conformation. However, the conformation of individual PEG bound to soft materials such as dendrimers has not been directly observed. Using atomic force microscopy (AFM) and scanning tunneling microscopy (STM), this work characterizes the structure adopted by PEGylated dendrimers with the highest resolution reported to date. AFM imaging enables visualization of the individual dendrimers, as well as the differentiation and characterization of the dendrimer core and PEG shell. STM provides direct imaging of the PEG extensions with high-resolution. Collectively, this investigation provides important insight into the structure of coated dendrimers, which is crucial for the design and development of better drug delivery vehicles.

Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection

“…The similar interaction between dendrimer and conjugated moieties has been discussed in other papers. (Riechers et al, 2015; Yang and da Rocha, 2014) Such a relatively compact structure may effectively protect the integrity of peptides from enzymatic degradation before delivery to immune cells or draining lymph nodes,(Etrych et al, 2011; Kurtoglu et al, 2010) which is one of major challenges for peptide vaccines to elicit/amplify immune responses. (Irvine et al, 2015; Oyewumi et al, 2010) Similar compact structures are observed in partially PEGylated PAMAM dendrimers.…”

“…(Irvine et al, 2015; Oyewumi et al, 2010) Similar compact structures are observed in partially PEGylated PAMAM dendrimers. (Riechers et al, 2015; Yang and da Rocha, 2014) Mixing Pep4 with dendrimer also seems to disrupt the aggregation of Pep4 (HD=9.6 nm) as indicated by the decrease in hydrodynamic diameter (HD=4.1 nm) and narrower size distribution (PDI changes from 0.225 to 0.159). However, non-covalent bonding in physical mixture is much weaker and susceptible to dissociation caused by physiological fluid.…”

“…The size and charge of the G4OH+Pep4 were observed to be similar to that of the conjugate, with a size much smaller than that observed for bare Pep4, indicating the formation of dendrimer/Pep4 complexes that serve well as controls to the conjugate. The positive charge of nanocarrier systems is known to enhance or facilitate cellular uptake via nonspecific adsorptive endocytosis and/or receptor-mediated endocytosis,(Albanese et al, 2012; Albertazzi et al, 2010; Kitchens et al, 2008; Nakanishi et al, 1999; Riechers et al, 2015; Win and Feng, 2005) and we thus believe the positive charge may also facilitate internalization of the G4OH-Pep4 nanovaccine and G4OH+Pep4 mixture into antigen-presenting cells (APCs).…”

Deciphering the Structure and Chemical Composition of Drug Nanocarriers: From Bulk Approaches to Individual Nanoparticle Characterization

“…For instance, the structure of poly(amidoamine) dendrimers has been imaged using platinum and copper metal ion tagging allowing a spatial resolution down to 0.2 nm. [89][90][91][92] In contrast to STM, AFM is suitable to characterize both conductive and insulating materials. The tip probes the local tip-surface interactions to map the sample topography and its physicochemical properties.…”

“…For instance, the structure of poly(amidoamine) dendrimers has been imaged using platinum and copper metal ion tagging allowing a spatial resolution down to 0.2 nm. [ 89–92 ]…”