Dong Choon Hyun

Engineered Nanoparticles for Drug Delivery in Cancer Therapy

In medicine, nanotechnology has sparked a rapidly growing interest as it promises to solve a number of issues associated with conventional therapeutic agents, including their poor water solubility (at least, for most anticancer drugs), lack of targeting capability, nonspecific distribution, systemic toxicity, and low therapeutic index. Over the past several decades, remarkable progress has been made in the development and application of engineered nanoparticles to treat cancer more effectively. For example, therapeutic agents have been integrated with nanoparticles engineered with optimal sizes, shapes, and surface properties to increase their solubility, prolong their circulation half-life, improve their biodistribution, and reduce their immunogenicity. Nanoparticles and their payloads have also been favorably delivered into tumors by taking advantage of the pathophysiological conditions, such as the enhanced permeability and retention effect, and the spatial variations in the pH value. Additionally, targeting ligands (e.g., small organic molecules, peptides, antibodies, and nucleic acids) have been added to the surface of nanoparticles to specifically target cancerous cells through selective binding to the receptors overexpressed on their surface. Furthermore, it has been demonstrated that multiple types of therapeutic drugs and/or diagnostic agents (e.g., contrast agents) could be delivered through the same carrier to enable combination therapy with a potential to overcome multidrug resistance, and real-time readout on the treatment efficacy. It is anticipated that precisely engineered nanoparticles will emerge as the next-generation platform for cancer therapy and many other biomedical applications.

Emerging Applications of Phase‐Change Materials (PCMs): Teaching an Old Dog New Tricks

The nebulous term phase-change material (PCM) simply refers to any substance that has a large heat of fusion and a sharp melting point. PCMs have been used for many years in commercial applications, mainly for heat management purposes. However, these fascinating materials have recently been rediscovered and applied to a broad range of technologies, such as smart drug delivery, information storage, barcoding, and detection. With the hope of kindling interest in this incredibly versatile range of materials, this Review presents an array of aspects related to the compositions, preparations, and emerging applications of PCMs.

Microscale Polymer Bottles Corked with a Phase‐Change Material for Temperature‐Controlled Release

Keep your wine chilled! Microscale polystyrene (PS) bottles are loaded with dye molecules and then corked with a phase-change material (PCM). When the temperature is raised beyond its melting point, the PCM quickly melts and triggers an instant release of the encapsulated dye. The release profiles can be manipulated by using a binary mixture of PCMs with different melting points.

A Polymeric Bowl for Multi‐Agent Delivery

This paper describes a simple system for multi-agent delivery. The system consists of a biodegradable polymer particle with a hollow interior, together with a hole on its surface that can be completely or partially sealed via thermal annealing. A hydrophobic dye, Nile-red, entrapped within the shell of hollow particles presents a sustained release behavior while methylene blue, a hydrophilic model agent, encapsulated in the hollow interior shows a fast release manner. The release profiles of the probes can be further independently controlled by encapsulating methylene blue-loaded polymer nanoparticles, instead of free dye, in the hollow particle with a small hole on its surface.

Micropatterning by controlled liquid instabilities and its applications

Robust, reproducible patterning over large areas is essential to the fabrication of miniaturized devices. When production and cost-efficiency are concerned, guided-assembly is a promising strategy for patterning that combines the advantages of both the top-down and bottom-up approaches. Most guided-assembly methods are enabled by controlling the instabilities of liquid solutions or polymer melts to be patterned. These instabilities can be observed in different ways according to the patterning strategies. This article reviews the strategies for micropatterning that are based on the manipulation of liquid instabilities, covering both physical principles and experimental demonstrations. Specifically, we discuss four types of liquid instabilities, which can be controlled for the reliable formation of micropatterns: (i) localization of the instability under an electric field, (ii) adjustment of the evaporation front line during solvent evaporation, (iii) template-directed selective dewetting, and (iv) hierarchical capillary instability for generating complex patterns. We also highlight future prospects of the instability-driven micropatterning techniques.

Protein capsules with cross-linked, semipermeable, and enzyme-degradable surface barriers for controlled release.

This paper describes a method for fabricating protein-based capsules with semipermeable and enzyme-degradable surface barriers. It involves the use of a simple fluidic device to generate water-in-oil emulsion droplets, followed by cross-linking of proteins at the water-oil interface to generate a semipermeable surface barrier. The capsules can be readily fabricated with uniform and controllable sizes and, more importantly, show selective permeability toward molecules with different molecular weights: small molecules like fluorescein sodium salt can freely diffuse through the surface barrier while macromolecules such as proteins can not. The proteins, however, can be released by digesting the surface barrier with an enzyme such as pepsin. Taken together, the capsules hold great potential for applications in controlled release, in particular, for the delivery of protein drugs.

Fabrication of monodisperse poly(ε-caprolactone) (PCL) particles using capillary force lithography (CFL)

This paper describes a new method for the fabrication of poly(e-caprolactone) (PCL) spherical particles with uniform, well-controlled diameters in the range of 100 to 900 nm. This method uses capillary force lithography (CFL) technique to pattern a thin film of PCL into an array of discrete disks, followed by their transformation into spherical beads under thermal annealing. When the diameter of the disks was fixed, the size of the resultant beads was only determined by the thickness of the PCL film. To demonstrate their use in the controlled release of a drug, an organic dye was loaded into the polymer particles. The loaded dye molecules could be released with different profiles depending on the crystalline microstructure of the polymer particles.

Poly(d,l-lactic-co-glycolic acid) (PLGA) hollow fiber with segmental switchability of its chains sensitive to NIR light for synergistic cancer therapy

This work introduces a new fibrous system for synergistic cancer therapy. The system consists of poly(d,l-lactic-co-glycolic acid) (PLGA) fibers with a core encapsulating an anticancer drug and a shell entrapping gold nanorods (AuNRs) as a photothermal agent. On exposure to NIR light, the photothermal agent generates heat to raise the local temperature of the fibers. If the temperature is above a glass transition (Tg) of the polymer, the polymer chains will be mobile, increasing free volume in size within the shell. As a result, a rapid release of the drug can be achieved. When NIR light is turned off, the release will stop with inactivity of the photothermal agent, followed by freezing the segmental motion of the polymer chains. The on-off switching of NIR light in a time-controllable manner allows a repeated and accurate release of the drug, leading to the significant enhancement of anticancer activity in combination with the hyperthermia effect arising from the photothermal agent.