Kang Dae Lee

Attenuation of the in vivo toxicity of biomaterials by polydopamine surface modification

AIMS Polydopamine coating is emerging as a useful method of surface functionalization due to the ability of this compound to form a nanometer-scale organic thin film on virtually any material surface to which proteins, peptides, oligonucleotides, metal ions or synthetic polymers are able to be attached. The unique properties of polydopamine make this technique suitable for nanomedicine. To facilitate the use of polydopamine, evaluation of toxicity is of great importance. In this article, we investigated the in vivo toxicity of polydopamine. RESULTS We found that the polydopamine functions as a biocompatible layer, attenuating adverse biological responses caused by intrinsic properties of the coated material. One-step polydopamine coating greatly reduced the inflammatory response to poly-L-lactic acid surfaces and the immunological responses of blood on quantum dots were also reduced. CONCLUSION Our results indicate that polydopamine provides a versatile platform that can reduce the in vivo toxicity of biomaterials that contact tissue or blood.

Catechol-Grafted Poly(ethylene glycol) for PEGylation on Versatile Substrates

We report on catechol-grafted poly(ethylene) glycol (PEG-g-catechol) for the preparation of nonfouling surfaces on versatile substrates including adhesion-resistant PTFE. PEG-g-catechol was prepared by the step-growth polymerization of PEO to which dopamine, a mussel-derived adhesive molecule, was conjugated. The immersion of substrates into an aqueous solution of PEG-g-catechol resulted in robust PEGylation on versatile surfaces of noble metals, oxides, and synthetic polymers. Surface PEGylation was unambiguously confirmed by various surface analytical tools such as ellipsometry, goniometry, infrared spectroscopy, and X-ray photoelectron spectroscopy. Contrary to existing PEG derivatives that are difficult-to-modify synthetic polymer surfaces, PEG-g-catechol can be considered to be a new class of PEGs for the facile surface PEGylation of various types of surfaces.

Target Delivery and Cell Imaging Using Hyaluronic Acid-Functionalized Graphene Quantum Dots

This work demonstrates the way to achieve efficient and target specific delivery of a graphene quantum dot (GQD) using hyaluronic acid (HA) (GQD-HA) as a targeting agent. HA has been anchored to a GQD that accepts the fascinating adhesive properties of the catechol moiety, dopamine hydrochloride, conjugated to HA, which was confirmed by X-ray photoelectron spectroscopy. Transmission electron microscopy revealed a particle size of ∼20 nm, and the fluorescence spectra revealed significant fluorescence intensity even after the anchoring of HA. The prepared GQD-HA was applied to CD44 receptor overexpressed tumor-bearing balb/c female mice, and the in vivo biodistribution investigation demonstrated more bright fluorescence from the tumor tissue. In vitro cellular imaging, via a confocal laser scanning microscope, exhibited strong fluorescence from CD44 overexpressed A549 cells. Both in vivo and in vitro results showed the effectiveness of using HA as targeting molecule. The loading and release kinetics of the hydrophobic drug doxorubicin from a GQD under mildly acidic conditions showed that a GQD can be considered as a novel drug carrier, while the nontoxic behavior from the MTT assay strongly supports the identification of GQD-HA as a biocompatible material.

Development of Disulfide Core-Crosslinked Pluronic Nanoparticles as an Effective Anticancer-Drug-Delivery System

Thiolated Pluronic (Plu-SH) nanoparticles are developed as potential articulate, target-specific anticancer-drug carriers for intracellular drug release triggered by the difference in redox potential in tumor cells. The cores of the micelles are formed by the disulfide bonds of the functionalized Pluronic F127, when dissolved in an aqueous solution. The nanoparticles are 95.6 ± 18.6 nm in size, and 235.6 ± 63.7 nm after encapsulation of the hydrophobic drug molecules. The drug-loaded micelles show effective stability in blood-plasma conditions and the kinetics of micelle stability and drug release are shown. Paclitaxel-loaded micelles display approximately 39% cell viability in A549 cells.

Functionalized biocompatible WO3 nanoparticles for triggered and targeted in vitro and in vivo photothermal therapy.

We report on dopamine-conjugated hyaluronic acid (HA-D), a mussel-inspired facile capping material that can modify tungsten oxide (WO3) nanoparticles to be both biocompatible and targetable, allowing precise delivery (WO3-HA) to a tumor site. Near-infrared (NIR) irradiated WO3-HA showed a rapid and substantial rise in photothermal heat to complete in vitro thermolysis of malignant MDAMB and A549 cancer cellsbut was found to be relatively less sensitive to normal MDCK cells. A long-term in vivo investigation of ~10 nm HA thickness on WO3 (WO3-HA) nanoparticles demonstrated efficient photo-thermal conversion with time-dependent tumor target accumulation. This long-termin vivo survival study ofWO3-HA showed promising biocompatibility, with a complete recovery from malignant tumor. Due to the importance of keeping simplicity in the design of therapeutic nanoparticles, we therefore expect that this facile scheme (HA-D) would contribute to the biocompatible development of versatile metallic nanoparticles for photothermal applications.

Photothermal conversion upon near-infrared irradiation of fluorescent carbon nanoparticles formed from carbonized polydopamine

Fluorescence and photothermal conversion mediated by near-infrared radiation (NIR) is reported for carbonized polydopamine nanoparticles. Carbonized polydopamine demonstrated excitation-dependent fluorescence emission, together with NIR-responsive photothermal conversion properties. The concentration-dependent photothermal heating from carbonized fluorescent carbon nanoparticles-polydopamine (FNP-pDA) induces hyperthermal killing of both cancer cell lines and bacteria in vitro. Although most of the dopamine moieties of polydopamine become dehydrated upon carbonization, the remaining dopamine-hydroxyl groups can confer adhesive properties. These fluorescent coatings are compatible with many substrates, and the surface passivation of FNP-pDA with polyethylene glycol improves quantum yield and extends fluorescence lifetimes. The novel infrared-responsive photothermal and fluorescent carbon nanoparticles reported here show promise for a range of potential biomedical and research applications.

Chlorin e6 conjugated silica nanoparticles for targeted and effective photodynamic therapy

Photodynamic therapy (PDT) using photosensitizer drug has become an important therapeutic modality. However, the stability and targeted delivery of photosensitizer remain a critical challenge for efficient PDT treatment. In the present study, we developed chlorin e6 (Ce6)-conjugated and folic acid (FA)-decorated silica nanoparticles (silica-Ce6-FA) for targeted delivery of photosensitizer to the cancer cells. The synthesized NPs exhibited excellent stability and biocompatibility with MDA-MB-231 cells. The formulated particles were efficiently taken up by folate receptor-positive MDA-MB-231 cells, which were confirmed by comparative analysis with folate receptor-negative HepG2 cells. The folate receptor-targeted silica-Ce6-FA was highly accumulated inside the MDA-MB-231 cells than free Ce6. The obtained NPs produced singlet oxygen efficiently under 670-nm laser exposure. The cell-killing effect of silica-Ce6-FA was higher when compared with free Ce6 under PDT treatment. The PDT-induced mitochondrial damage and apoptotic cell death were detected in silica-Ce6-FA-treated cells.

Design of Surface-Coatable NIR-Responsive Fluorescent Nanoparticles with PEI Passivation for Bacterial Detection and Killing

The ability to quickly detect and kill bacteria is crucial in the realm of antibiotic resistance. In this study, we synthesized a detection probe consisting of polyethylenimine (PEI)-passivated polydopamine-based fluorescent carbon (FDA:PEI) nanoparticles, generating a cationic adhesive material for bacterial detection that is surface-coatable, photothermal, and antibacterial. The cationic FDA:PEI nanoparticles effectively bound to the anionic bacterial cell wall, resulting in a dramatic quenching effect visible in fluorescence spectra and confocal images. In this fluorescence on/off system, FDA:PEI nanoparticles showed similar bacterial detection abilities between aqueous- and solid-phase assays. Scanning electron microscopy clearly showed the attachment of FDA:PEI nanoparticles to the surface of bacteria, both in solution and as a coating on the surface of a polypropylene film. In addition to detection, this versatile material was found to have an antibacterial potential, via near-infrared irradiation to induce a heat release, killing bacteria by thermolysis. Thus, by exploiting the cationic and catechol moieties on the surface of polydopamine carbon dots, we developed a novel bacterial-detection platform that can be used in a broad range of conditions.

Multimodal tumor-homing chitosan oligosaccharide-coated biocompatible palladium nanoparticles for photo-based imaging and therapy

Palladium, a near-infrared plasmonic material has been recognized for its use in photothermal therapy as an alternative to gold nanomaterials. However, its potential application has not been explored well in biomedical applications. In the present study, palladium nanoparticles were synthesized and the surface of the particles was successfully modified with chitosan oligosaccharide (COS), which improved the biocompatibility of the particles. More importantly, the particles were functionalized with RGD peptide, which improves particle accumulation in MDA-MB-231 breast cancer cells and results in enhanced photothermal therapeutic effects under an 808-nm laser. The RGD peptide-linked, COS-coated palladium nanoparticles (Pd@COS-RGD) have good biocompatibility, water dispersity, and colloidal and physiological stability. They destroy the tumor effectively under 808-nm laser illumination at 2 W cm−2 power density. Further, Pd@COS-RGD gives good amplitude of photoacoustic signals, which facilitates the imaging of tumor tissues using a non-invasive photoacoustic tomography system. Finally, the fabricated Pd@COS-RGD acts as an ideal nanotheranostic agent for enhanced imaging and therapy of tumors using a non-invasive near-infrared laser.

Magnetic hydroxyapatite: a promising multifunctional platform for nanomedicine application

In this review, specific attention is paid to the development of nanostructured magnetic hydroxyapatite (MHAp) and its potential application in controlled drug/gene delivery, tissue engineering, magnetic hyperthermia treatment, and the development of contrast agents for magnetic resonance imaging. Both magnetite and hydroxyapatite materials have excellent prospects in nanomedicine with multifunctional therapeutic approaches. To date, many research articles have focused on biomedical applications of nanomaterials because of which it is very difficult to focus on any particular type of nanomaterial. This study is possibly the first effort to emphasize on the comprehensive assessment of MHAp nanostructures for biomedical applications supported with very recent experimental studies. From basic concepts to the real-life applications, the relevant characteristics of magnetic biomaterials are patented which are briefly discussed. The potential therapeutic and diagnostic ability of MHAp-nanostructured materials make them an ideal platform for future nanomedicine. We hope that this advanced review will provide a better understanding of MHAp and its important features to utilize it as a promising material for multifunctional biomedical applications.