Yunok Oh

Doxorubicin-loaded fucoidan capped gold nanoparticles for drug delivery and photoacoustic imaging.

Polymer nanoparticles are emerging as a useful tool for a wide variety of biomedical and therapeutic applications. The present study demonstrates the multifunctional doxorubicin-loaded fucoidan capped gold nanoparticles (DOX-Fu AuNPs) for drug delivery and photoacoustic imaging (PAI). Biocompatible AuNPs were synthesized using a naturally occurring fucoidan (Fu) as a capping and reducing agent. The Fu AuNPs synthesis was determined using UV-visible spectrum, and it was further characterized using high resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis. The release of DOX from DOX-Fu AuNPs was greater in acidic pH (4.5) than in neutral pH (7.4). The in vitro cytotoxic effect of fucoidan, Fu AuNPs, DOX, and DOX-Fu AuNPs inhibited the proliferation of human breast cancer cells with an inhibitory concentration of 35μg/mL, 30μg/mL, 15μg/mL, and 5μg/mL at 24h. DOX-Fu AuNPs induced both early and late apoptosis in a concentration-dependent manner compared with untreated control cells. The ability of DOX-Fu AuNPs as a contrast agent for in vitro breast cancer imaging with PAI has been evaluated. These results suggest that the multifunctional DOX-Fu AuNPs for drug delivery and PAI can soon provide considerable contribution to human health.

In vitro study on apoptotic cell death by effective magnetic hyperthermia with chitosan-coated MnFe₂O₄.

Magnetic nanoparticles (MNPs) have been widely investigated as a hyperthermic agent for cancer treatment. In this study, thermally responsive Chitosan-coated MnFe2O4 (Chitosan-MnFe2O4) nanoparticles were developed to conduct localized magnetic hyperthermia for cancer treatment. Hydrophobic MnFe2O4 nanoparticles were synthesized via thermal decomposition and modified with 2,3-dimercaptosuccinic acid (DMSA) for further conjugation of chitosan. Chitosan-MnFe2O4 nanoparticles exhibited high magnetization and excellent biocompatibility along with low cell cytotoxicity. During magnetic hyperthermia treatment (MHT) with Chitosan-MnFe2O4 on MDA-MB 231 cancer cells, the targeted therapeutic temperature was achieved by directly controlling the strength of the external AC magnetic fields. In vitro Chitosan-MnFe2O4-assisted MHT at 42 °C led to drastic and irreversible changes in cell morphology and eventual cellular death in association with the induction of apoptosis through heat dissipation from the excited magnetic nanoparticles. Therefore, the Chitosan-MnFe2O4 nanoparticles with high biocompatibility and thermal capability can be an effective nano-mediated agent for MHT on cancer.

Multifunctional biocompatible chitosan-polypyrrole nanocomposites as novel agents for photoacoustic imaging-guided photothermal ablation of cancer

Cancer nanotechnology is emerging as one of the promising strategies combining photothermal therapy (PTT) and photoacoustic imaging (PAI) for the treatment of breast cancer and it has received considerable attention in the recent years because it is minimally invasive, prevents damage to non-targeted regions, permits fast recovery, and involves breast cancer imaging. The present study demonstrates multifunctional biocompatible chitosan-polypyrrole nanocomposites (CS-PPy NCs) as novel agents for photoacoustic imaging-guided photothermal ablation of cancer because of their biocompatibility, conductivity, stability, and strong near-infrared (NIR) absorbance. The CS-PPy NCs are spherical in shape and range 26–94 nm in size with a mean value of 50.54 ± 2.56 nm. The in vitro results demonstrated good biocompatibility of CS-PPy NCs, which can be used in PTT for cancer cells under 808-nm NIR laser irradiation. Tumor-bearing mice fully recovered after treatment with CS-PPy NCs and NIR 808-nm laser irradiation compared to the corresponding control groups. Our research highlights the promising potential of using CS-PPy NCs for photoacoustic imaging-guided photothermal ablation of cancer in preclinical animals, which should be verified in future clinical trials.

Intravascular ultrasonic-photoacoustic (IVUP) endoscope with 2.2-mm diameter catheter for medical imaging.

Intravascular ultrasound (IVUS) imaging is extremely important for detection and characterization of high-risk atherosclerotic plaques as well as gastrointestinal diseases. Recently, intravascular photoacoustic (IVPA) imaging has been used to differentiate the composition of biological tissues with high optical contrast and ultrasonic resolution. The combination of these imaging techniques could provide morphological information and molecular screening to characterize abnormal tissues, which would help physicians to ensure vital therapeutic value and prognostic significance for patients before commencing therapy. In this study, integration of a high-frequency IVUS imaging catheter (45MHz, single-element, unfocused, 0.7mm in diameter) with a multi-mode optical fiber (0.6mm in core diameter, 0.22 NA), an integrated intravascular ultrasonic-photoacoustic (IVUP) imaging catheter, was developed to provide spatial and functional information on light distribution in a turbid sample. Simultaneously, IVUS imaging was co-registered to IVPA imaging to construct 3D volumetric sample images. In a phantom study, a polyvinyl alcohol (PVA) tissue-mimicking arterial vessel phantom with indocyanine green (ICG) and methylene blue (MB) inclusion was used to demonstrate the feasibility of mapping the biological dyes, which are used in cardiovascular and cancer diagnostics. For the ex vivo study, an excised sample of pig intestine with ICG was utilized to target the biomarkers present in the gastrointestinal tumors or the atherosclerotic plaques with the proposed hybrid technique. The results indicated that IVUP endoscope with the 2.2-mm diameter catheter could be a useful tool for medical imaging.

Synthesis of amine-polyglycidol functionalised Fe3O4@SiO2 nanocomposites for magnetic hyperthermia, pH-responsive drug delivery, and bioimaging applications

The combined chemotherapy and thermal therapy is mainly considered in clinical applications in cancer therapy. However, the preparation of multifunctional nanomaterials is an attractive approach for cancer treatment. In this report, we present the synthesis of amine-polyglycidol functional shell modified-silica coated-magnetic iron oxide nanocomposites (Fe3O4@SiO2@APG-F) for a FITC conjugated drug carrier system and/or hyperthermia agent in cancer therapy. The Fe3O4@SiO2@APG-F nanocomposite exhibits superparamagnetic properties with a magnetic saturation value of approximately 17.2 emu g−1. The magnetic hyperthermia experiment shows a very fast temperature increase within a short time (45 °C in 4.5 min) when applying an alternating magnetic field (AMF), which is considered to be an appropriate temperature for the localized hyperthermia treatment in cancer therapy. Further, the fluorescein isothiocyanate (FITC), a model fluoropore, was conjugated with the terminal amine groups of the Fe3O4@SiO2@APG to endow the green fluorescent behavior that may be desirable for biological imaging applications. The Fe3O4@SiO2@APG-F material shows high drug loading efficiency and the MTT assay results evidenced that the synthesised Fe3O4@SiO2@APG-F nanocomposites are biocompatible. The fluorescence microscopic images show the particles can be effectively taken up by cancer cells. Therefore, the FITC conjugated Fe3O4@SiO2@APG-F nanocomposites that possess a magnetic core covered by silica coating, organic APG functional shell, and FITC fluorophore together in a single entity could serve as a good hyperthermia agent, drug delivery carrier, and fluorescent contrast agent for bioimaging. Thus, the Fe3O4@SiO2@APG-F nanocomposite could be considered as a promising material to be used in multimodal cancer therapy.

Photothermal-triggered control of sub-cellular drug accumulation using doxorubicin-loaded single-walled carbon nanotubes for the effective killing of human breast cancer cells

Single-walled carbon nanotubes (SWNTs) are often the subject of investigation as effective photothermal therapy (PTT) agents owing to their unique strong optical absorption. Doxorubicin (DOX)-loaded SWNTs (SWNTs-DOX) can be used as an efficient therapeutic agent for combined near infrared (NIR) cancer photothermal and chemotherapy. However, SWNTs-DOX-mediated induction of cancer cell death has not been fully investigated, particularly the reaction of DOX inside cancer cells by PTT. In this study, we examined how the SWNTs-DOX promoted effective MDA-MB-231 cell death compared to DOX and PTT alone. We successfully synthesized the SWNTs-DOX. The SWNTs-DOX exhibited a slow DOX release, which was accelerated by NIR irradiation. Furthermore, DOX released from the SWNTs-DOX accumulated inside the cells at high concentration and effectively localized into the MDA-MB-231 cell nucleus. A combination of SWNTs-DOX and PTT promoted an effective MDA-MB-231 cell death by mitochondrial disruption and ROS generation. Thus, SWNTs-DOX can be utilized as an excellent anticancer agent for early breast cancer treatment.

pH and NIR-light-responsive magnetic iron oxide nanoparticles for mitochondria-mediated apoptotic cell death induced by chemo-photothermal therapy

Recently, various therapeutic strategies in anticancer drug development are focused to reduce adverse side effects and to enhance the therapeutic efficacy. Mostly, the iron oxide (Fe3O4) nanoparticles have widely been utilized as an efficient drug delivery system towing to their unique properties such as excellent magnetic behavior, considerably low toxicity, easy surface modification and high drug-loading efficacy. In the present study, we synthesized a multifunctional, DMSA coated, water soluble Fe3O4 nanoparticles (Fe3O4@DMSA/DOX) for an effective pH and NIR-light triggered delivery of anticancer drug (DOX) in cancer therapy. The combination of photothermal therapy combined with chemotherapy results demonstrated that the synthesized Fe3O4@DMSA/DOX is an excellent candidate for pH- and NIR-light induced phothothermal agent for an effective delivery of anticancer drug (DOX) into the target sub-cellular level into the human breast cancer (MDA-MB-231) cells. Furthermore, the Fe3O4@DMSA/DOX nanoparticles induced an excellent temperature elevation upon NIR light irradiation and controlled DOX release in vitro. The Fe3O4@DMSA/DOX nanoparticles exhibited synergistic effect when combining chemotherapy with photothermal therapy and showed an excellent cell toxicity to MDA-MB-231 cells. In addition, the combined chemo-photothermal therapy of Fe3O4@DMSA/DOX nanoparticles promoted an effective cell death by mitochondrial disruption mediated by ROS generation. Thus, the synthesized Fe3O4@DMSA/DOX nanoparticles could be utilized as potential anticancer agents for breast cancer treatment.

Anti-EGFR Antibody Conjugation of Fucoidan-Coated Gold Nanorods as Novel Photothermal Ablation Agents for Cancer Therapy

The development of novel photothermal ablation agents as cancer nanotheranostics has received a great deal of attention in recent decades. Biocompatible fucoidan (Fu) is used as the coating material for gold nanorods (AuNRs) and subsequently conjugated with monoclonal antibodies against epidermal growth factor receptor (anti-EGFR) as novel photothermal ablation agents for cancer nanotheranostics because of their excellent biocompatibility, biodegradability, nontoxicity, water solubility, photostability, ease of surface modification, strongly enhanced absorption in near-infrared (NIR) regions, target specificity, minimal invasiveness, fast recovery, and prevention of damage to normal tissues. Anti-EGFR Fu-AuNRs have an average particle size of 96.37 ± 3.73 nm. Under 808 nm NIR laser at 2 W/cm2 for 5 min, the temperature of the solution containing anti-EGFR Fu-AuNRs (30 μg/mL) increased by 52.1 °C. The anti-EGFR Fu-AuNRs exhibited high efficiency for the ablation of MDA-MB-231 cells in vitro. In vivo photothermal ablation exhibited that tumor tissues fully recovered without recurrence and finally were reconstructed with normal tissues by the 808 nm NIR laser irradiation after injection of anti-EGFR Fu-AuNRs. These results suggest that the anti-EGFR Fu-AuNRs would be novel photoablation agents for future cancer nanotheranostics.

Marine Biopolymer-Based Nanomaterials as a Novel Platform for Theranostic Applications

ABSTRACT Marine biopolymer-based nanomaterials are one of the most active research areas in recent decades for theranostic applications. Marine biopolymers are interesting biomaterials for clinical applications because of their good biocompatibility, biodegradability, inexpensiveness, abundance, stability, ease of surface modification, and nontoxic nature. New nanoparticles in development are coated with marine polymers to combine therapeutic and diagnostic (theranostic) applications because of the strongly enhanced absorption and scattering in near-infrared (NIR) regions. In this review, the use of marine biopolymer-based nanomaterials for theranostic applications is evaluated, addressing potential applications in drug delivery, photothermal therapy (PTT), photodynamic therapy (PDT), hyperthermia therapy, photoacoustic imaging (PAI), magnetic resonance imaging (MRI), and computed tomography (CT). In addition, the most recent progress in the biocompatibility of marine biopolymer-based nanomaterials in vitro and in vivo are discussed, along with a promising future scope for the treatment of major life-threatening diseases such as cancer.

Cytotoxic Induction and Photoacoustic Imaging of Breast Cancer Cells Using Astaxanthin-Reduced Gold Nanoparticles

Astaxanthin, a kind of photosynthetic pigment, was employed for gold nanoparticle formation. Nanoparticles were characterized using Ulteraviolet-Visible (UV-Vis) spectroscopy, transmission electron microscopy, and X-ray diffraction, and the possible presence of astaxanthin functional groups were analyzed by Fourier transform infrared spectroscopy (FTIR). The cytotoxic effect of synthesized nanoparticles was evaluated against MDA-MB-231 (human breast cancer cells) using a tetrazolium-based assay, and synthesized nanoparticles exhibited dose-dependent toxicity. The morphology upon cell death was differentiated through fluorescent microscopy using different stains that predicted apoptosis. The synthesized nanoparticles were applied in ultrasound-coupled photoacoustic imaging to obtain good images of treated cells. Astaxanthin-reduced gold nanoparticle has the potential to act as a promising agent in the field of photo-based diagnosis and therapy.