Sung Young Park

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.

Recyclable and stable silver deposited magnetic nanoparticles with poly (vinyl pyrrolidone)-catechol coated iron oxide for antimicrobial activity.

This paper introduces a facile method to make highly stable and recyclable antimicrobial magnetic nanoparticles (NPs). Initially, magnetic iron oxide nanoparticles (IONPs) were coated with poly (vinyl pyrrolidone) conjugated catechol (PVP-CCDP). Afterward, silver nanoparticles (Ag(0)) were deposited onto PVP-CCDP coated IONPs using remain catechol. The prepared nanoparticles showed long term (~4 weeks) colloidal stability and redispersibility, respectively, against external magnetic field and over a broad range of pH (4-12). The NPs were characterized by UV-vis, SEM, XPS, and XRD measurements. TEM and DLS analyses showed that the mean particle size of PVP-CCDP coated IONPs/Ag(0) were about 72 nm. The recyclable magnetic NPs possessed a high antibacterial effect against the model microbes Staphylococcus aureus and Escherichia coli and could be separated easily using magnet following antibacterial test for repeated uses and maintained 100% antibacterial efficiency during three cycles. In MTT assay, the magnetic nanoparticles possessed no measureable cytotoxicity to live cells.

Target delivery of β-cyclodextrin/paclitaxel complexed fluorescent carbon nanoparticles: externally NIR light and internally pH sensitive-mediated release of paclitaxel with bio-imaging

The development of cooperative drug delivery systems that can detect and target the disease site, with rapid trigger controlled drug release (internally and externally), is widely expected to change the landscape of future drug carriers. In this study a drug delivery system was developed for the cancer-targeted release of chemotherapeutic agents inside living cells. This system is an environment sensitive (pH), and external photothermally remote controlled, cooperative image-guided drug delivery matrix. Partially carbonized fluorescence hyaluronic acid (HA-FCN) was conjugated with boronic acid (BA) to promote the formation of boronate ester with diol groups of β-cyclodextrin (CD) [HA-FCN-CD]. The pH influence mediated release of paclitaxel (PTX) from the CD cavity of HA-FCN-CD was utilized for targeted cancer bioimaging. This active-target delivery system (HA-FCN-CD-PTX) was found to show optical absorption properties similar to those of the near infrared (NIR) light sensitive carbonized material. This system exploits acidity for triggered drug release and rapid generation of mild photothermal heat to trigger burst release of PTX. Cooperative guided bioimaging that employs both internal pH responsive and external NIR controlled drug carriers is a promising method for chemotherapeutic release that can be adjusted according to physiological needs.

In Vitro and In Vivo Tumor Targeted Photothermal Cancer Therapy Using Functionalized Graphene Nanoparticles

Despite the tremendous progress that photothermal therapy (PTT) has recently achieved, it still has a long way to go to gain the effective targeted photothermal ablation of tumor cells. Driven by this need, we describe a new class of targeted photothermal therapeutic agents for cancer cells with pH responsive bioimaging using near-infrared dye (NIR) IR825, conjugated poly(ethylene glycol)-g-poly(dimethylaminoethyl methacrylate) (PEG-g-PDMA, PgP), and hyaluronic acid (HA) anchored reduced graphene oxide (rGO) hybrid nanoparticles. The obtained rGO nanoparticles (PgP/HA-rGO) showed pH-dependent fluorescence emission and excellent near-infrared (NIR) irradiation of cancer cells targeted in vitro to provide cytotoxicity. Using intravenously administered PTT agents, the time-dependent in vivo tumor target accumulation was exactly defined, presenting eminent photothermal conversion at 4 and 8 h post-injection, which was demonstrated from the ex vivo biodistribution of tumors. These tumor environment responsive hybrid nanoparticles generated photothermal heat, which caused dominant suppression of tumor growth. The histopathological studies obtained by H&E staining demonstrated complete healing from malignant tumor. In an area of limited successes in cancer therapy, our translation will pave the road to design stimulus environment responsive targeted PTT agents for the safe eradication of devastating cancer.

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.

Photoresponsive Fluorescent Reduced Graphene Oxide by Spiropyran Conjugated Hyaluronic Acid for in Vivo Imaging and Target Delivery

This present article demonstrates the strategy to prepare photoresponsive reduced graphene oxide with mussel inspired adhesive material dopamine (DN) and photochromic dye spiropyran (SP) conjugated to the backbone of the targeting ligand hyaluronic acid (HA; HA-SP). Graphene oxide (GO) was reduced by prepared HA-SP accepting the advantages of catechol chemistry under mildly alkaline condition enabling to achieve functionalized graphene (rGO/HA-SP) as fluorescent nanoparticles. Due to containing HA, rGO/HA-SP can bind to the CD44 cell receptors. The prepared rGO/HA-SP is able to retain its photochromic features and can be converted to merocyanine (MC) form upon irradiation with UV light (wavelength: 365 nm) displaying purple color. Photochromic behavior of rGO/HA-SP was monitored by UV-vis and fluorescence spectroscopy. In vitro fluorescence behavior, examined by confocal laser scanning microscope (CLSM), of rGO/HA-SP in cancerous A549 cell lines assured that efficient delivery of rGO/HA-SP was gained due to HA as targeting ligand. In this work, we have shown that in vivo fluorescence image of spiropyran is possible by administrating MC form solution of rGO/HA-SP using Balb/C mice as in vivo modal. Accumulation of rGO/HA-SP in tumor tissue from biodistribution analysis strongly supports the specific delivery of prepared graphene to the target destination. The well tuned drug release manner from the surface of rGO/HA-SP strongly recommends the developed material not only as fluorescent probe for diagnosis but also as a drug carrier in drug delivery system.

Iron Oxide@PEDOT-Based Recyclable Photothermal Nanoparticles with Poly(vinylpyrrolidone) Sulfobetaines for Rapid and Effective Antibacterial Activity.

Growing microbial resistance that renders antibiotic treatment vulnerable has emerged, attracting a great deal of interest in the need to develop alternative antimicrobial treatments. To contribute to this effort, we report magnetic iron oxide (Fe3O4) nanoparticles (NPs) coated with catechol-conjugated poly(vinylpyrrolidone) sulfobetaines (C-PVPS). This negatively charged Fe3O4@C-PVPS is subsequently encapsulated by poly(3,4-ethylenedioxythiophene) (PEDOT) following a layer-by-layer (LBL) self-assembly method. The obtained Fe3O4@C-PVPS:PEDOT nanoparticles appear to be novel NIR-irradiated photothermal agents that can achieve effective bacterial killing and are reusable after isolation of the used particles using external magnetic fields. The recyclable Fe3O4@C-PVPS:PEDOT NPs exhibit a high efficiency in converting photothermal heat for rapid antibacterial effects against Staphylococcus aureus and Escherichia coli. In this study, antibacterial tests for repeated uses maintained almost 100% antibacterial efficiency during three cycles and provided rapid and effective killing of 99% Gram-positive and -negative bacteria within 5 min of near-infrared (NIR) light exposure. The core-shell nanoparticles (Fe3O4@C-PVPS:PEDOT) exhibit the required stability, and their paramagnetic nature means that they rapidly convert photothermal heat sufficient for use as NIR-irradiated antibacterial photothermal sterilizing agents.