Jaejung Song

Gold nanoparticle-mediated photothermal therapy: current status and future perspective

Gold nanoparticles (AuNPs) are attractive photothermal agents for cancer therapy because they show efficient local heating upon excitation of surface plasmon oscillations. The strong absorption, efficient heat conversion, high photostability, inherent low toxicity and well-defined surface chemistry of AuNPs contribute to the growing interest in their photothermal therapy (PTT) applications. The facile tunability of gold nanostructures enables engineering of AuNPs for superior near-infrared photothermal efficacy and target selectivity, which guarantee efficient and deep tissue-penetrating PTT with mitigated concerns regarding side effects by nonspecific distributions. This article discusses the current research findings with representative near-infrared-active AuNPs, which include nanoshell, nanorod, nanocage, nanostar, nanopopcorn and nanoparticle assembly systems. AuNPs successfully demonstrate potential for use in PTT, but several hurdles to clinical applications remain, including long-term toxicity and a need for sophisticated control over biodistribution and clearance. Future research directions are discussed, especially regarding the clinical translation of AuNP photosensitizers.

Mesenchymal Stem Cells Aggregate and Deliver Gold Nanoparticles to Tumors for Photothermal Therapy

Gold nanoparticles (AuNPs) have been extensively studied for photothermal cancer therapy because AuNPs can generate heat upon near-infrared irradiation. However, improving their tumor-targeting efficiency and optimizing the nanoparticle size for maximizing the photothermal effect remain challenging. We demonstrate that mesenchymal stem cells (MSCs) can aggregate pH-sensitive gold nanoparticles (PSAuNPs) in mildly acidic endosomes, target tumors, and be used for photothermal therapy. These aggregated structures had a higher cellular retention in comparison to pH-insensitive, control AuNPs (cAuNPs), which is important for the cell-based delivery process. PSAuNP-laden MSCs (MSC-PSAuNPs) injected intravenously to tumor-bearing mice show a 37-fold higher tumor-targeting efficiency (5.6% of the injected dose) and 8.3 °C higher heat generation compared to injections of cAuNPs after irradiation, which results in a significantly enhanced anticancer effect.

Light-responsible DNA hydrogel–gold nanoparticle assembly for synergistic cancer therapy

Assembled AuNPs in a DNA hydrogel (Dgel) showed strongly coupled plasmon modes, and the Dgel vehicle can co-load anticancer drugs such as doxorubicin (Dox) as a light-controlled releasing cargo by DNA intercalations. Upon laser excitation, local heat shock generation was accompanied by the release of Dox. A highly synergistic combination of thermo- and chemotherapy was demonstrated in cellular and animal models. Our Dgel vehicle can be fragmented after the excitation-induced heat generations, which subsequently causes the dispersion of the AuNPs. Our system may be less toxic because it uses small sizes of AuNPs, and the inherently biocompatible scaffold may reduce the long-term toxicity by rapid clearance.

DNA hydrogel templated carbon nanotube and polyaniline assembly and its applications for electrochemical energy storage devices

Functional nanocomposites comprising of biomaterials and non-biomaterials are one of the main subjects of recent research due to their wide range of potential applications. Here, we demonstrate that the porous DNA hydrogel (Dgel) can be an excellent template for combining carbon nanotubes (CNTs) and polyaniline (PANI) resulting in high performance supercapacitor electrodes. These hybrid supercapacitors have been constructed by electrostatic deposition of conductive CNTs on DNA hydrogel followed by coating of PANI pseudocapacitor. Performances of supercapacitors in terms of specific capacitance, cycling stability, power density, and energy density have been systematically investigated. The specific capacitance of these DNA hydrogel based supercapacitors has reached up to 146.4 F g−1 with a power density of 23.3 kW kg−1 and an energy density of 13.0 Wh kg−1 in acidic media which is higher than commercially available products. In addition, the cytotoxicity of our supercapacitors was evaluated in vitro in cell culture media during the charge–discharge processes. In both human and mouse skin cell culture media, our devices exhibited zero cytotoxicity. Our novel biological hybrid electrodes can be a platform towards biocompatible and implantable energy storage devices for in vivo applications.

A sub 6 nanometer plasmonic gold nanoparticle for pH-responsive near-infrared photothermal cancer therapy

A small (sub 6 nm hydrodynamic size) and pH-responsive gold nanoparticle photothermal agent is reported, which can respond to changes in pH and form aggregates. The coupled plasmon mode of aggregates can be efficiently exploited for photothermal cancer therapy using longer excitation wavelength.

Cancer-Microenvironment-Sensitive Activatable Quantum Dot Probe in the Second Near-Infrared Window

Recent technological advances have expanded fluorescence (FL) imaging into the second near-infrared region (NIR-II; wavelength = 1000-1700 nm), providing high spatial resolution through deep tissues. However, bright and compact fluorophores are rare in this region, and sophisticated control over NIR-II probes has not been fully achieved yet. Herein, we report an enzyme-activatable NIR-II probe that exhibits FL upon matrix metalloprotease activity in tumor microenvironment. Bright and stable PbS/CdS/ZnS core/shell/shell quantum dots (QDs) were synthesized as a model NIR-II fluorophore, and activatable modulators were attached to exploit photoexcited electron transfer (PET) quenching. The quasi type-II QD band alignment allowed rapid and effective FL modulations with the compact surface ligand modulator that contains methylene blue PET quencher. The modulator was optimized to afford full enzyme accessibility and high activation signal surge upon the enzyme activity. Using a colon cancer mouse model, the probe demonstrated selective FL activation at tumor sites with 3-fold signal enhancement in 10 min. Optical phantom experiments confirmed the advantages of the NIR-II probe over conventional dyes in the first near-infrared region.

Super-resolution visible photoactivated atomic force microscopy

Imaging the intrinsic optical absorption properties of nanomaterials with optical microscopy (OM) is hindered by the optical diffraction limit and intrinsically poor sensitivity. Thus, expensive and destructive electron microscopy (EM) has been commonly used to examine the morphologies of nanostructures. Further, while nanoscale fluorescence OM has become crucial for investigating the morphologies and functions of intracellular specimens, this modality is not suitable for imaging optical absorption and requires the use of possibly undesirable exogenous fluorescent molecules for biological samples. Here we demonstrate super-resolution visible photoactivated atomic force microscopy (pAFM), which can sense intrinsic optical absorption with ~8 nm resolution. Thus, the resolution can be improved down to ~8 nm. This system can detect not only the first harmonic response, but also the higher harmonic response using the nonlinear effect. The thermoelastic effects induced by pulsed laser irradiation allow us to obtain visible pAFM images of single gold nanospheres, various nanowires, and biological cells, all with nanoscale resolution. Unlike expensive EM, the visible pAFM system can be simply implemented by adding an optical excitation sub-system to a commercial atomic force microscope.

DNA templated synthesis of branched gold nanostructures with highly efficient near-infrared photothermal therapeutic effects

Herein, we show that DNA nanostructures have great potential as templates for the synthesis of shape-controlled metal nanostructures. In specific, branch-shaped gold nanostructures, which show broad absorption in near the infrared region and have high efficacy in photothermal cancer cell treatment, have been successfully synthesized by using X-shaped and Y-shaped DNA as templates.

A RNA producing DNA hydrogel as a platform for a high performance RNA interference system

RNA interference (RNAi) is a mechanism in which small interfering RNA (siRNA) silences a target gene. Herein, we describe a DNA hydrogel capable of producing siRNA and interfering with protein expression. This RNAi-exhibiting gel (termed I-gel for interfering gel) consists of a plasmid carrying the gene transcribing siRNA against the target mRNA as part of the gel scaffold. The RNAi efficiency of the I-gel has been confirmed by green fluorescent protein (GFP) expression assay and RNA production quantification. The plasmid stability in the I-gel results in an 8-times higher transcription efficiency than that of the free plasmid. We further applied the I-gel to live cells and confirmed its effect in interfering with the GFP expression. The I-gel shows higher RNAi effect than plasmids in free form or complexed with Lipofectamine. This nanoscale hydrogel, which is able to produce RNA in a cell, provides a platform technology for efficient RNAi system.Interfering RNA have a range of therapeutic and research based applications, issues with delivery have made systems that make siRNA in situ of interest. Here, the author report on the creation of a DNA hydrogel with improved stability and transcription efficiency over plasmid DNA.

Electrostatic interaction driven gold nanoparticle assembly on three-dimensional triangular pyramid DNA nanostructures

Here we show that well-defined three dimensional DNA nanostructures can be synthesized from branched DNAs via hybridization and enzymatic ligation. The fabricated triangular pyramid DNA has been employed as a template for assembly of AuNPs. The electrostatic attraction between DNA structures and AuNPs has shown nonspecific assembly behavior and allowed the plasmonic absorption peaks of the assembled nanocomposites to be tuned from visible to near infrared by simple control of the mixing ratio.