Kyoung Sub Kim

A cancer-recognizable MRI contrast agents using pH-responsive polymeric micelle.

A cancer-recognizable MRI contrast agents (CR-CAs) has been developed using pH-responsive polymeric micelles. The CR-CAs with pH sensitivity were self-assembled based on well-defined amphiphilic block copolymers, consisting of methoxy poly(ethylene glycol)-b-poly(L-histidine) (PEG-p(L-His)) and methoxy poly(ethylene glycol)-b-poly(L-lactic acid)-diethylenetriaminopentaacetic acid dianhydride-gadolinium chelate (PEG-p(L-LA)-DTPA-Gd). The CR-CAs have a spherical shape with a uniform size of ~40 nm at physiological pH (pH 7.4). However, in acidic tumoral environment (pH 6.5), the CR-CAs were destabilized due to the protonation of the imidazole groups of p(L-His) blocks, causing them to break apart into positively charged water-soluble polymers. As a result, the CR-CAs exhibit highly effective T1 MR contrast enhancement in the tumor region, which enabled the detection of small tumors of ~3 mm(3 )in vivo at 1.5 T within a few minutes.

Cancer cell specific targeting of nanogels from acetylated hyaluronic acid with low molecular weight.

In order to develop a novel self-assembly as a means of cancer cell targeting, self-organized nanogels were prepared from acetylated hyaluronic acid with low molecular weight (AC-HA(LM)). Three samples were obtained (AC-HA(LM)1, 2 and 3) with degrees of acetylation, 0.8, 2.1, or 2.6 acetyl groups per unit (2 glucose rings) of HA(LM) to control their hydrophobicity. The mean diameters of AC-HA(LM)2 and 3 were less than 300 nm with unimodal size distribution, while that of AC-HA(LM)1 was above 400 nm. The critical aggregation concentrations (CAC) of the nanogels in distilled water were < 1 x 10(-1) mg/mL. The doxorubicine (DOX) loading efficiencies and loading contents of AC-HA(LM) increased as the degree of acetylation increased, in particular, the loading efficiency of AC-HA(LM)3 reached above 90%. AC-HA(LM)3 nanogels showed IC(50) at 1300 ng/mL of the DOX concentration against HeLa cells (with HA-binding receptors) similar to free DOX. For monitoring of specific interaction with a carcinoma cell line (HeLa cells with HA-binding receptors), AC-HA(LM)3 was labeled with FITC and observed with a confocal microscope. HeLa cells were strongly luminated by interactions with fluorescence-labeled AC-HA(LM)3 nanogels; however, this luminance was significantly decreased by competition inhibition of free HA. This result indicates that modified HA maintains the ability to interact with HA-binding receptors. The selective cytotoxicity and interaction of AC-HA(LM) nanogels may help reduce side effects of anti-cancer drugs in clinical use.

Multi-modal transfection agent based on monodisperse magnetic nanoparticles for stem cell gene delivery and tracking

Directing the controlled differentiation and tracking of stem cells is essential to achieve successful stem cell therapy. In this work, we describe a multi-modal (MR/optical) transfection agent (MTA) for efficient gene delivery and cell tracking of human mesenchymal stem cells (hMSCs). The MTA was synthesized through a facile two-step approach with 1) ligand exchange of a catechol-functionalized polypeptide (CFP) and 2) chemical immobilization of fluorescence labelled cationic polymer via aminolysis reaction. Cationic polymer-immobilized MTAs with size of ~40 nm exhibit greatly enhanced colloidal stability in aqueous solution. In addition, the MTAs were capable of binding DNA molecules for transfection. The MTA/pDNA complex showed relatively good transfection efficiency in hMSCs (compared to the commercial transfection agent, Lipofectamine) and good biocompatibility. MTA-treated hMSCs were successfully visualized after transplantation via MR and optical imaging system over 14 days. These studies highlight the challenges associated with the potential advantages of designing multi-modal nanostructured materials as tools for genetic materials delivery and cell-tracking in stem cell therapy.

Caffeic acid-coated multifunctional magnetic nanoparticles for the treatment and bimodal imaging of tumours.

Accurate theragnosis of tumour is essential for improving the life rate of tumour patients. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used as both diagnostic and therapeutic agents. However, their application is often limited because of a lack of water solubility, lack of cancer treatment efficacy, and ineffective targeting of tumour cells. In this report, a double ligand (caffeic acid-polyethylene glycol-folic acid; FA-PEG-CA, caffeic acid-polyethylene glycol-pheophorbide-a; PheoA-PEG-CA) coated iron oxide nanoparticle has been fabricated that overcomes the limitations of conventional SPION. Photosensitizer and tumour targeting ligands were coated on SPION using a ligand-substitution method. We confirmed the successful substitution of oleic acid ligands with FA-PEG-CA and PheoA-PEG-CA ligands by FT-IR spectroscopy. The caffeic acid coated iron oxide nanoparticles (CAMNPs) also demonstrated high water solubility in an aqueous environment and folate-mediated active tumour targeting. The water solubility of CAMNPs was evaluated by DLS measurement and TEM images. The cytotoxicity of CAMNPs increased two-fold in MDA-MB-231 cells at a laser irradiation condition. The fabricated CAMNPs retained their ability to function as both MRI diagnostic and tumour-selective therapeutic agents. These results suggest that these efficient characteristics of CAMNPs can be incorporated into applications, thus enhancing the efficacy of clinical cancer treatment.

Vitamin Bc-Bearing Hydrophilic Photosensitizer Conjugate for Photodynamic Cancer Theranostics

The accurate diagnosis and proper therapy for cancer are essential to improve the success rate of cancer treatment. Here, we demonstrated that the vitamin Bc -bearing hydrophilic photosensitizer conjugate folic acid-polyethylene glycol-pheophorbideA (FA-PEG-PheoA) has been synthesized for the intracellular diagnosis and photodynamic therapy of a tumor. The synthesized vitamin Bc -bearing hydrophilic photosensitizer conjugate has been characterized for the folic acid receptor expressing the ability to target tumor cells, which is facilitated by the chemical conjugation with folic acid. The vitamin Bc -bearing hydrophilic photosensitizer conjugate internalization mechanism was identified through a competitive inhibition test with free folic acid. We optimized the laser-sensitive, cytotoxicity changeable, vitamin Bc -bearing hydrophilic photosensitizer conjugate concentration, which is non-cytotoxic under normal conditions and specifically cytotoxic toward cancer cells (maximum 69.15%) under laser irradiation conditions used for theranostic agents. The cancer therapeutic and diagnosis effects of synthesized conjugate were confirmed in MDA-MB-231 cells and MDA-MB-231-bearing mice. As a result, the vitamin Bc -bearing hydrophilic photosensitizer conjugate exhibited a highly photodynamic therapeutic effect, which enabled the selective detection of a folic acid receptor expressing cancer using optical imaging.