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Dahwun KIM,Su Yeon LIM,Siyan LYU,Oui Bo WHANG,Chae Eun PARK,Byung Deok KIM,Ji Hoon JEONG 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
Regenerative medicine and tissue engineering have been developed by human mesenchymal stem cells (hMSCs) with self-renewal and multipotency. However, the in vivo differentiation of hMSCs to an undesirable cell type decreases clinical efficacy. There is a clinical need to develop a method to prevent the unwanted differentiation and to resolve clinical unmet needs. Genetic engineering may direct hMSCS to appropriate differentiation with improved clinical efficacy. One of the major challenges for genetic modification is an inefficient and unsafe gene delivery system. This research synthesized bioinspired calcium phosphate (CaP)-based nanoparticles stabilized with a catechol-derivatized hyaluronic acid (dopa-HA) conjugate as a non-viral gene carrier for gene transfection to hMSCs for inducing differentiation in a desired cell type. Since bone marrow-derived hMSCS express CD44 receptors on their cell surface, and HA is a specific ligand for CD44, dopa-HA/CaP achieved higher intracellular uptake in hMSCs than branched polyethylenimine (bPEI, MW 25 kDa) with no cytotoxic effects. Dopa-HA/CaP nanoparticles formed a stable complex with a plasmid DNA encoding bone morphogenetic protein 2 (BMP-2 pDNA) and microRNA 148b (miRNA-148b). In addition, they were successfully accumulated in hMSCs and induced osteogenesis via increasing level of BMP-2, bone-forming growth factor, and suppression of Noggin, an antagonist for BMP-regulated osteogenic differentiation.
Chemoattractant releasing microneedles for enhanced DNA vaccination
Nak Won Kim,Su Yeon Lim,Dahwun Kim,Siyan Lyu,Ouibo Whang,Chaeeun Park,Byung Deok Kim,이민상,정지훈 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.117 No.-
Transcutaneous delivery of a DNA vaccine using microneedle (MN) has attracted much attention sincethere are a variety of immune cells underneath the skin. However, the clinical use of DNA vaccine is limiteddue to its poor cellular uptake of naked plasmid DNA (pDNA) and suboptimal presentation of an antigenby antigen presenting cells (APC). Herein, we designed a MN system for delivering polyplex-basedDNA vaccine and recruiting APCs by a chemoattractant N-formyl-methionyl-leucyl-phenylalanine peptide(fMLP)-releasing microspheres (fMLP-MS) using MN coated with pH-responsive polyelectrolyte multilayerassembly (PMA). The PMA can be rapidly disrupted upon the application of MN to the skin, leadingto the release of polyplex and fMLP-MS. The polyplex would be taken up by the epidermal cells and residentAPCs to express and secrete the antigen (amyloid beta monomer, Ab1-42) encoded in the DNA vaccine. fMLP released from fMLP-MS could recruit APCs to the site of MN administration by chemotacticeffects. The MN-based vaccination system was able to induce robust antigen-specific antibodyproduction.
SuYeon LIM,Dahwun KIM,SiYan LYU,OuiBo HWANG,ByungDeok KIM,ChaeEun PARK,Ji hoon JEONG 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
Microneedle (MN) has been desired as a therapeutic device which allow cutaneous administration of various drugs with easily and painlessly. Herein, nano-micelle generating dissolvable MN was designed by a biocompatible amphiphilic tri-block copolymer. When fabricating with doxorubicin (DOX) in the MN, the hydrophobic anticancer drug can be dissolved in an aqueous medium by entrapped in nano-micelles generated by dissolution of the MN. The intratumoral administration of the DOX-encapsulated MN can significantly inhibit the growth of melanoma in a mouse skin cancer model. Furthermore, owing to its small size (< 50 ㎚), the nano-micelle can efficiently migrate to the sentinel lymph nodes, killing the metastatic skin cancer cells. Therefore, the use of locally application of MN can be considered as a promising therapeutic device for the inhibition of metastatic melanoma.
Hoon Jeong JI,Min Sang LEE,Su Yeon LIM,Dahwun KIM,SiYan LYU,Oui bo WHANG,Chaeeun PARK,Byung Deok KIM 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
Recently, the potential toxicity of nanomaterials has attracted a great number of attention, because materials in nano-scale dimensions frequently display substantially dissimilar properties compared to manufactured materials with the same composition and may have unpredicted adverse effects on cells and tissues. A wide range of inorganic or organic nanoparticles with diameters of a few hundred nanometers have been reported to cause oxidative injury, inflammatory responses, cellular cytotoxicity, or genotoxicity. A major mechanism responsible for these adverse effects is thought to relate oxidative stress, which is often the result of excess intracellular reactive oxygen species (ROS). In this study, we developed an antioxidative transfection system minimizing cellular oxidative stress for enhanced transfection.