Multimodal Golden DNA Superstructures (GDSs) for Highly Efficient Photothermal Immunotherapy.

DNA-templated metallization has emerged as an efficient strategy for creating nanoscale-metal DNA hybrid structures with a desirable conformation and function. Despite the potential of DNA-metal hybrids, their use as combinatory therapeutic agents has rarely been examined. Herein, we present a simple approach for fabricating a multipurpose DNA superstructure that serves as an efficient photoimmunotherapy agent. Specifically, we adsorb and locally concentrate Au ions onto DNA superstructures through induced local reduction, resulting in the formation of Au nanoclusters. The mechanical and optical properties of these metallic nanoclusters can be rationally controlled by their conformations and metal ions. The resulting golden DNA superstructures (GDSs) exhibit significant photothermal effects that induce cancer cell apoptosis. When sequence-specific immunostimulatory effects of DNA are combined, GDSs provide a synergistic effect to eradicate cancer and inhibit metastasis, demonstrating potential as a combinatory therapeutic agent for tumor treatment. Altogether, the DNA superstructure-templated metal casting system offers promising materials for future biomedical applications.

A microfluidic device with 3-d hydrogel villi scaffold to simulate intestinal absorption.

The absorption of drugs via oral route is a subject of a great interest in drug development process. The current in vitro method for measuring the kinetics of drug absorption relies on 2-D monolayer culture of Caco-2 cells on a porous membrane, but physiologically unrealistic environment provided by this method often results in inaccurate drug absorption kinetics. Here we report a novel microfluidic system which better mimics the physiological environment of the human small intestine. Three dimensional geometries of villi of the small intestine were reproduced via novel hydrogel microfabrication technique, and the fluid flow in the apical and basolateral sides of intestinal tract was reproduced with a two-layer microfluidic device. A wide range of flow rates was achieved by using gravity-induced flow, potentially facilitating easier high-throughput implementation. The kinetics of diffusion process through the 3-D villi scaffold in the microfluidic device was measured and mathematically modeled. When combined with intestinal cell culture model, this novel 3-D microfluidic system can serve as an in vitro platform that better mimics the in vivo environment.

Organ-on-a-chip technology and microfluidic whole-body models for pharmacokinetic drug toxicity screening.

Microscale cell culture platforms better mimic the in vivo cellular microenvironment than conventional, macroscale systems. Microscale cultures therefore elicit a more authentic response from cultured cells, enabling physiologically realistic in vitro tissue models to be constructed. The fabrication of interconnecting microchambers and microchannels allows drug absorption, distribution, metabolism and elimination to be simulated, and enables precise manipulation of fluid flow to replicate blood circulation. Complex, multi-organ interactions can be investigated using "organ-on-a-chip" toxicology screens. By reproducing the dynamics of multi-organ interaction, the dynamics of various diseases and drug activities can be studied in mechanistic detail. In this review, we summarize the current status of technologies related to pharmacokinetic-based drug toxicity testing, and the use of microtechnology for reproducing the interaction between multiple organs.