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Treatment of Cancer with Dissolving Microneedles Array Using Immunomodulators and Antigens
Oui Bo WHANG,Su Yeon LIM,Da Whun KIM,Siyan LYN,Byung Deok KIM,Chae Eun PARK,Ji Hoon JEONG 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
A Microneedle (MN) is a micron-sized needle that can penetrate directly through the epidermal layer to the skin tissue without pain. As a therapeutic agent, MNs are widely used in transdermal drug delivery system (TDDS) because they are convenient, reduce side effect, and painless. Many kinds of MNs have been applied for deliver anti-cancer drug, gene or protein. In recent years, Dissolving MNs (DMNs) are studied for targeting cancer cells. Using dissolving MNs not only improves the drug bioavailability, but also reduces the first-pass effect on the liver. Imidazoquinoline is used for anti-allergic and anti-viral immune-modulator in a way to regulate immune response. In this study, we report pluronic-based DMNs which could form nano sized micelles with the hydrophobic molecule. Here, resiquimod (R848) and ovalbumin (OVA) were encapsulated in the DMNs to treat cancer. Treatment with DMNs containing adjuvant (R848) and antigen (OVA) to the skin of EG7-OVA tumor-injected mice, induced a significant level of antigen-specific humoral and cellular immunity, resulting in significant anti-cancer activity.
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.
Siyan LYU,Su Yeon LIM,Byung Deok KIM,Da Whun KIM,Chae Eun PARK,Oui Bo WHANG,Ji Hoon JEONG 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
Among the various material, poly (lactic-co-glycolic acid) (PLGA) is mainly used in the formation of sustained release microspheres due to its biodegradability, compatibility, and safety. In this study, we confirmed the treatment ability of AMD, a diease which is caused by vascular endothelial growth factor (VEGF) signaling system, by using the PLGA sustained release of microspheres. The anti-VEGF drug, Rivoceranib was encapsulated through o/w single emulsion and solvent evaporation method with polymeric excipients PLGA. In vivo study, the treatment of microspheres of PLGA/rivoceranib significantly inhibits the occurrence and spread of new blood vessels in the macular degeneration model. These results suggest that the treatment of sustained release microsphere with rivoceranib can be one strategy to treat the wet AMD through drug repositioning.
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.
Enhanced Systemic siRNA Delivery Using Reducible Bile Acid-modified PEI for Cancer Therapy
Chae eun PARK,Su yeon LIM,Da hwun KIM,Siyan LYU,Byung deok KIM,Oui bo WHANG,Ji hoon JEONG 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
Small interfering RNA (siRNA) contributes to RNA interference(RNAi) by inhibiting target gene expression in a sequence-specific manner. siRNA delivery system have become increasingly popular for cancer therapy. In this study, we used a low molecular weight polyethylenimine (PEI, 1.8 kDa) conjugated with deoxycholic acid (DA). A DA-PEI conjugate was further modified with 4-fluorothiophenol (4-FTP) (4-FTP-DA-PEI) to enhance systemic siRNA delivery. The thiophenol group would be involved with disulfide bonds between the polymer chains and siRNA modified with free thiols (thiol-siRNA) to form and π-π interactions between the pendent aromatic groups and coprostane ring of the bile acid. The stabilized TP-DA-PEI conjugate with thiol-siRNA achieved developed intracellular uptake, serum stability, and transfection efficiency. Furthermore, it shows high accumulation of TP-DA-PEI/thiol-siRNA polyplexes and significant tumor growth inhibition effect in tumor-bearing mice after systemic administration.