Despite the prediction by molecular dynamics simulations [23–25] that drug molecules may attach to both the exterior and interior of dendrimers, the direct evidence from experiments is still lacking due to difficulties in visualizing

intramolecular structures of dendrimers. Scanning tunneling microscopy (STM), due to its high spatial resolution, offers a promising solution to this challenge [26]. The highest spatial resolution is typically reported for conductive and semiconductive systems, reaching the submolecular level [27]. Using metal ion coordination [28, 29], Inhibitors,research,lifescience,medical we extended the high-resolution capability of STM to dendrimers in this investigation, resolving individual indomethacin molecules at the dendrimer exterior. In the case of telodendrimer Inhibitors,research,lifescience,medical micelles, dynamic light scattering (DLS) allows the average diameter and distribution to be determined in the solution phase [16, 17]. Individual Z-VAD-FMK 187389-52-2 micelles may be visualized using cryotransmission electron microscopy (cryo-TEM) upon freezing of the samples. The use of cryo-TEM is complicated, as the micelles are no longer in their natural environment [30]. A much Inhibitors,research,lifescience,medical simpler technique, atomic force microscopy (AFM), could offer some remedy to this pursuit. AFM offers high spatial resolution and versatility

of imaging in various media, including micelle formation media and selleck Ixazomib physiological buffers [31–33]. In this study, we have tested the feasibility and demonstrated the proof-of-concept of using scanning probe microscopy to image PTX-loaded thiol Inhibitors,research,lifescience,medical modified telodendrimer micelles, HS-PEG5k-CA8 (“5k”, represents the molecular weight of PEG, and “8” indicates the number of CA subunits in the telodendrimer), in aqueous media where micelles form. The results are very encouraging: individual micelles are clearly visualized, from which we can extract the size and geometry of micelles in correlation with the conditions

of assembly. The difference between native and drug carrying micelles is clearly visible under AFM, from which the drug carrying capacity can be estimated. In addition, the knowledge of the geometry and size Inhibitors,research,lifescience,medical of individual micelles facilitates our understanding of their efficacy and further optimization. 2. Materials and Methods 2.1. Materials Paclitaxel was purchased from AK scientific Inc. 4th generation hydroxyl-terminated poly(amidoamine) Brefeldin_A dendrimers, G4 PAMAM-OH (98% purity, 10% by weight in methanol), and 1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-3-indoleacetic acid, commonly known as indomethacin (≥99.0%), were purchased from Sigma-Aldrich and used without further purification. 1-adamantanethiol (AD, 95% purity) and n-octanethiol (C8, 98% purity) were purchased from Sigma-Aldrich and used as received. 200 proof ethanol (99.99% purity) was purchased from Gold Shield Chemical Co. K2PtCl4 (min. 42.4% Pt, Alfa Aesar) was used as received. Ultrapure water (≥8MΩ·cm) was obtained using a Millipore Milli-Q filtration system.