Renal Clearable Ru-based Coordination Polymer Nanodots for Photoacoustic Imaging Guided Cancer Therapy.

Rationale: Despite the promises of applying theranostic nanoagents for imaging-guided cancer therapy, the chronic retention of these nanoagents may cause safety concerns that hinder their future clinical applications. The metabolizable nanoagents with rapid renal excretion to avoid long-term toxicity is a possible solution for this issue. Method: Herein, we synthesize ultra-small metal-organic coordination polymer nanodots based on ruthenium ion (Ru3+) / phenanthroline (Phen) (Ru-Phen CPNs) with superior near-infrared (NIR) absorption. The size, photothermal conversion, cytotoxicity, photoacoustic imaging, in vivo & in vitro cancer treatment efficiency and biosafety are tested. Results: The size of the ultra-small Ru-Phen CPNs is 6.5 nm. The photothermal conversion efficiency is measured to be ~ 60.69 %, much higher than that of previously reported photothermal agents. The Ru-Phen CPNs could be employed for photoacoustic (PA, 808 nm) imaging-guided photothermal therapy (PTT, 808 nm, 0.5 W/cm2) with great performance. Notably, the intrinsic PA signals (808 nm) of Ru-Phen CPNs are observed in kidneys of treated mice, illustrating efficient renal clearance of those ultra-small CPNs. Moreover, the clearance of CPNs is further confirmed by detecting Ru levels in urine and feces. Conclusion: Our work presents a new type of ultra-small Ru-based CPNs with a record high photothermal conversion efficiency, efficient tumor retention after systemic administration, and rapid renal excretion to avoid long-term toxicity, promising for imaging-guided photothermal therapy.

Graphene Oxide Selectively Enhances Thermostability of Trypsin.

In the past few years, graphene and its derivative, graphene oxide (GO), have been extensively studied for their applications in biotechnology. In our previous work, we reported certain PEGylated GOs (GO-PEGs) can selectively promote trypsin activity and enhance its thermostability. To further explore this, here we synthesized a series of GO-PEGs with varying PEGylation degrees. Enzymatic activity assay shows that both GO and GO-PEGs can protect trypsin, but not chymotrypsin, from thermal denaturation at high temperature. Surprisingly, the lower the PEGylation degree, the better the protection, and GO as well as the GO-PEG with the lowest PEGylation degree show the highest protection efficiency (∼70% retained activity at 70 °C). Fluorescence spectroscopy analysis shows that GO/GO-PEGs have strong interactions with trypsin. Molecular Dynamics (MD) simulation results reveal that trypsin is adsorbed onto the surface of GO through its cationic residues and hydrophilic residues. Different from chymotrypsin adsorbed on GO, the active site of trypsin is covered by GO. MD simulation at high temperature shows that, through such interaction with GO, trypsin's active site is therefore stabilized and protected by GO. Our work not only illustrates the promising potential of GO/GO-PEGs as efficient, selective modulators for trypsin, but also provides the interaction mechanism of GO with specific proteins at the nano-bio interface.

Computational simulation of drug delivery at molecular level.

The field of drug delivery is advancing rapidly. By controlling the precise level and/or location of a given drug in the body, side effects are reduced, doses are lowered, and new therapies are possible. Nonetheless, substantial challenges remain for delivering specific drugs into specific cells. Computational methods to predict the binding and dynamics between drug molecule and its carrier are increasingly desirable to minimize the investment in drug design and development. Significant progress in computational simulation is making it possible to understand the mechanism of drug delivery. This review summarizes the computational methods and progress of four categories of drug delivery systems: dendrimers, polymer micelle, liposome and carbon nanotubes. Computational simulations are particularly valuable in designing better drug carriers and addressing issues that are difficult to be explored by laboratory experiments, such as diffusion, dynamics, etc.

Efficiency of various lattices from hard ball to soft ball: theoretical study of thermodynamic properties of dendrimer liquid crystal from atomistic simulation.

Self-assembled supramolecular organic liquid crystal structures at nanoscale have potential applications in molecular electronics, photonics, and porous nanomaterials. Most of these structures are formed by aggregation of soft spherical supramolecules, which have soft coronas and overlap each other in the packing process. Our main focus here is to study the possible packing mechanisms via molecular dynamics simulations at the atomistic level. We consider the relative stability of various lattices packed by the soft dendrimer balls, first synthesized and characterized by Percec et al. (J. Am. Chem. Soc. 1997, 119, 1539) with different packing methods. The dendrons, which form the soft dendrimer balls, have the character of a hard aromatic region from the point of the cone to the edge with C(12) alkane "hair". After the dendrons pack into a sphere, the core of the sphere has the hard aromatic groups, while the surface is covered with the C(12) alkane "hair". In our studies, we propose three ways to organize the hair on the balls, Smooth/Valentino balls, Sticky/Einstein balls, and Asymmetric/Punk balls, which lead to three different packing mechanisms, Slippery, Sticky, and Anisotropic, respectively. We carry out a series of molecular dynamics (MD) studies on three plausible crystal structures (A15, FCC, and BCC) as a function of density and analyze the MD based on the vibrational density of state (DoS) method to extract the enthalpy, entropy, and free energies of these systems. We find that anisotropic packed A15 is favored over FCC, BCC lattices. Our predicted X-ray intensities of the best structures are in excellent agreement with experiment. "Anisotropic ball packing" proposed here plays an intermediate role between the enthalpy-favored "disk packing" and entropy-favored "isotropic ball packing", which explains the phase transitions at different temperatures. Free energies of various lattices at different densities are essentially the same, indicating that the preferred lattice is not determined during the packing process. Both enthalpy and entropy decrease as the density increases. Free energy change with volume shows two stable phases: the condensed phase and the isolated micelle phase. The interactions between the soft dendrimer balls are found to be lattice dependent when described by a two-body potential because the soft ball self-adjusts its shape and interaction in different lattices. The shape of the free energy potential is similar to that of the "square shoulder potential". A model explaining the packing efficiency of ideal soft balls in various lattices is proposed in terms of geometrical consideration.