Myoung-Hwan Park

Nanoparticles for detection and diagnosis

Nanoparticle based platforms for identification of chemical and biological agents offer substantial benefits to biomedical and environmental science. These platforms benefit from the availability of a wide variety of core materials as well as the unique physical and chemical properties of these nanoscale materials. This review surveys some of the emerging approaches in the field of nanoparticle based detection systems, highlighting the nanoparticle based screening methods for metal ions, proteins, nucleic acids, and biologically relevant small molecules.

Enhanced Isolation and Release of Circulating Tumor Cells Using Nanoparticle Binding and Ligand Exchange in a Microfluidic Chip

The detection of rare circulating tumor cells (CTCs) in the blood of cancer patients has the potential to be a powerful and noninvasive method for examining metastasis, evaluating prognosis, assessing tumor sensitivity to drugs, and monitoring therapeutic outcomes. In this study, we have developed an efficient strategy to isolate CTCs from the blood of breast cancer patients using a microfluidic immune-affinity approach. Additionally, to gain further access to these rare cells for downstream characterization, our strategy allows for easy detachment of the captured CTCs from the substrate without compromising cell viability or the ability to employ next generation RNA sequencing for the identification of specific breast cancer genes. To achieve this, a chemical ligand-exchange reaction was engineered to release cells attached to a gold nanoparticle coating bound to the surface of a herringbone microfluidic chip (NP-HBCTC-Chip). Compared to the use of the unmodified HBCTC-Chip, our approach provides several advantages, including enhanced capture efficiency and recovery of isolated CTCs.

Controlled and Sustained Release of Drugs from Dendrimer-Nanoparticle Composite Films

A dendrimer-nanoparticle hybrid scaffold based on robust dithiocarbamate formation provides a controlled drug delivery system. These composite films are nontoxic and can incorporate a variety of guests, providing sustained drug release over multiple uses. The system is highly modular: the release process can be easily tuned by altering the dendrimer generation and the size of the AuNPs, generating a versatile delivery system.

Multimonth controlled small molecule release from biodegradable thin films.

Significance Drug release from implants and coatings provides a means for local administration while minimizing systemic toxicity. Controlled release can provide a slowly eluting drug reservoir to maintain elevated therapeutic levels. Devices based on degradable polymer matrices can control drug release for multiple weeks, but longer durations typically require bulky, nondegradable devices. Using a combination of a polymer–drug conjugate and its electrostatic thin film assembly, we discovered a predictable long-term sustained release of more than 14 mo, far exceeding the duration noted in most previous reports, especially those from biodegradable matrices. Because of the substantial drug loading, nanoscale films were able to maintain significant concentrations that remained highly potent. We report a versatile, long-term drug delivery platform with broad biomedical implications. Long-term, localized delivery of small molecules from a biodegradable thin film is challenging owing to their low molecular weight and poor charge density. Accomplishing highly extended controlled release can facilitate high therapeutic levels in specific regions of the body while significantly reducing the toxicity to vital organs typically caused by systemic administration and decreasing the need for medical intervention because of its long-lasting release. Also important is the ability to achieve high drug loadings in thin film coatings to allow incorporation of significant drug amounts on implant surfaces. Here we report a sustained release formulation for small molecules based on a soluble charged polymer–drug conjugate that is immobilized into nanoscale, conformal, layer-by-layer assembled films applicable to a variety of substrate surfaces. We measured a highly predictable sustained drug release from a polymer thin film coating of 0.5–2.7 μm that continued for more than 14 mo with physiologically relevant drug concentrations, providing an important drug delivery advance. We demonstrated this effect with a potent small molecule nonsteroidal anti-inflammatory drug, diclofenac, because this drug can be used to address chronic pain, osteoarthritis, and a range of other critical medical issues.

Chemoselective Nanoporous Membranes via Chemically Directed Assembly of Nanoparticles and Dendrimers

Chemoselective nanoporous membranes: tunably porous membranes with embedded functionalities are generated using a template-free, chemically directed nanoparticle-dendrimer (NP-Den) network assembly. This approach provides a direction in the design of post-functionalizable nanoporous membranes for distinguishing both organic molecules and proteins with excellent chemo- and bioselectivity.

Chemically Directed Immobilization of Nanoparticles onto Gold Substrates for Orthogonal Assembly Using Dithiocarbamate Bond Formation

Dithiocarbamate-mediated bond formation combined with soft lithography was used for the selective immobilization of amine-functionalized silica nanoparticles on gold substrates. The available amine groups on the upper surface of the immobilized silica nanoparticles were further utilized for postdeposition of additional materials including particles, dyes, and biomolecules. The robustness of dithiocarbamate-mediated immobilization enables orthogonal assembly on surfaces via selective removal of the masking thiol ligands using iodine vapor etching followed by further functionalization.

Metal Nanoparticle Wires Formed by an Integrated Nanomolding−Chemical Assembly Process: Fabrication and Properties

We report here the use of nanomolding in capillaries (NAMIC) coupled with dithiocarbamate (DTC) chemistry to fabricate sub-50 nm quasi-1D arrays of 3.5 nm core gold nanoparticles (Au NPs) over large areas. Owing to chemical immobilization via the DTC bond, the patterned NP systems are stable in water and organic solvents, thus allowing the surface modification of the patterned Au NP arrays through thiol chemistry and further orthogonal binding of proteins. The electrical properties of these patterned Au NP wires have also been studied. Our results show that NAMIC combined with surface chemistry is a simple but powerful tool to create metal NP arrays that can potentially be applied to fabricate nanoelectronic or biosensing devices.

Nanoparticle–dendrimer hybrid nanocapsules for therapeutic delivery

BACKGROUND Nanocapsules can efficiently encapsulate therapeutic cargo for anticancer drug delivery. However, the controlled release of the payload remains a challenge for effective drug delivery. MATERIALS & METHODS We used dithiocarbamate-functionalized PAMAM dendrimer to cross-link the shell of arginine gold nanoparticles stabilized nanocapsule, and controlled the drug release from the nanocapsule. The ability of cross-linked nanocapsule to deliver hydrophobic paclitaxel to B16F10 cells was demonstrated both in vitro and in vivo. RESULTS Cross-linked nanocapsule possesses tunable stability and modular permeability, and can deliver paclitaxel with improved anticancer efficiency compared with free drug both in vitro and in vivo. CONCLUSION Dithiocarbamate chemistry provides a new tool to harness multifactorial colloidal self-assembly for controlled drug delivery for cancer therapy.

Accessibility of cylindrical channels within patterned mesoporous silica films using nanoparticle diffusion

Mesoporous silica films with well ordered nanochannels (approximately 7 nm in diameter) oriented parallel to the substrate were synthesized using supercritical carbon dioxide mediated silica deposition within templates comprised of triblock copolymers blended with strongly associating homopolymers. The films were patterned at the device level by conventional lithography and etched to yield periodic circular features approximately 20 µm in diameter. The nanoscale channels remained accessible to penetrant diffusion as shown by dye uptake experiments. The nanochannel arrays were used as miniature size exclusion columns to mediate nanoparticle diffusion.

Replenishable dendrimer-nanoparticle hybrid membranes for sustained release of therapeutics.

We report a versatile hybrid membrane for sustained release therapeutic delivery systems. Chemically-directed assembly of a hybrid membrane of nanoparticles and dendrimers was integrated with a fluidic delivery device and a refillable drug reservoir, providing continuous sustained release.