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육심명,변영로,정지헌 한국고분자학회 2014 Macromolecular Research Vol.22 No.8
One of the major obstacles to successful intraportal islet transplantation is the early portal vein embolizationelicited by the infused islets. Thus, reducing the size and the number of islets is an important process to alleviatethe damage of liver after intraportal islet transplantation. In our previous studies, we developed a strategy to constructgenetically modified islet cell clusters (ICCs) and demonstrated their superiority in maintaining better viabilityand functionality in vivo. In this study, signal-peptide linked exendin-4 transduced islet cell clusters (Sp-Ex-4 ICCs)were used to reverse diabetes after intraportal islet transplantation in hyperglycemic mouse model. Group of micereceiving 500 islet equivalent (IEQ) of unmodified ICCs failed to restore normoglycemia following transplantation. Although 500 IEQ of ICCs was insufficient to reverse hyperglycemia in diabetic mice, no significant acute liverdamage or life-threatening liver embolization was observed. When 1000 IEQ ICCs were infused into the portal vein,all animals died within 24 h post-surgery. In order to clarify the effect of Sp-Ex-4 gene transduction in improvingICCs functionality, 500 IEQ of Sp-Ex-4 ICCs were infused into the portal vein of diabetic mice. Following transplantation,75% of diabetic mice returned to normoglycemia and the survival fraction was 100%. In conclusion, intraportaltransplantation of Sp-Ex-4 ICCs successfully reversed diabetes in hyperglycemic mice by reducing the mass requiredfor the treatment. Therefore, intraportal transplantation of small islets (genetically engineered ICCs) can be proposedas a new strategy to overcome early graft embolization after intraportal transplantation.
정지헌,육심명,변영로 한국고분자학회 2016 Macromolecular Research Vol.24 No.11
Improvements in preventing pancreatic islet rejection are needed for successful treatment of type 1 diabetes. Our objective was to develop an optimized protocol combining modification of islets with polyethyleneglycol (PEG) chains and administration of tacrolimus (FK506, Prograf), an immunosuppressive drug for preventing rejection following transplantation. Freshly isolated islets were incubated with different concentrations (0.25, 1.00, 10.00, and 25.00%) of FITC-labeled mPEG-SCM (MW. 20 KDa) for various incubation times. 1% mPEG-SCM incubated with islets for 1 h is optimized surface coverage condition without cell toxicity. In addition, in order to optimize the concentration of tacrolimus (FK506, Prograf), different concentrations (0.1, 0.5 or 2.0 mg/kg) were injected into the diabetic mice following transplantation of PEGylated islets. The PEGylated islet survival time in mice injected daily with 0.1 mg/kg and 0.5 mg/kg of tacrolimus was significantly better than in the group without tacrolimus injection. The graft survival time in mice injected daily with 2.00 mg/kg of exhibited no prolonged survival time. Finally, immunohistochemical staining of left kidney containing PEGylated islets (injected with 0.1 mg/kg of tacrolimus) demonstrated strong staining for insulin, glucagon, and somatostatin but very weak CD20 staining was observed in the islet transplanted area. In conclusion, 1% mPEG-SCM incubated with islets for 1 h was the optimal condition for PEGylation without affecting the cell viability. A dose of tacrolimus between 0.1-0.5 mg/kg was highly effective for inhibiting immune cell activation. These results are promising for their application in developing a novel immunosuppressive protocol for successful pancreatic islet transplantation in the treatment of type 1 diabetes.
Ramesh Duwa,정지헌,육심명 한국공업화학회 2021 Journal of Industrial and Engineering Chemistry Vol.94 No.-
Ovarian cancer is the most significant cause of gynecological cancer mortality, with the majority ofwomen with advanced disease. Although surgery and chemotherapy can enhance survival rates, the 5-year survival [2TD$DIF]rates remain low at 45%. So, alternative treatment options need to be implemented toimprove therapeutic outcomes. In the ovarian cancer tumor, the presence of T cells helps to improve theprogression-free and overall survival, whereas a poor prognosis corresponds to the presence ofregulatory T cells and expression of T cells inhibitory molecules. Analyzing the important role of theseimmune systems in cancer management, immunotherapy may create a sustained response to recurringovarian cancer cells in the immune system. In addition, by boosting anti-tumor immune response,women’s prognosis with this lethal disease can be significantly influenced. Different immunotherapeuticstrategies and nanoparticle-based strategies were used as potential treatment options to challengetumor progression. This review discusses cytokine therapy, peptide vaccine, monoclonal antibody,dendritic cell-based vaccine, adoptive T cells transfer, and immune checkpoint inhibitors as well asdifferent nanoparticles such as poly (lactic-co-glycolic) acid nanoparticles, polyethyleneimine-basednanoparticles, and liposomes that offer a new paradigm in the treatment of ovarian cancer.
Polymeric and lipid-based drug delivery systems for treatment of glioblastoma multiforme
Ramesh Duwa,Fakhrossadat Emami,이수연,정지헌,육심명 한국공업화학회 2019 Journal of Industrial and Engineering Chemistry Vol.79 No.-
Glioblastoma multiforme (GBM) is the most aggressive, malignant brain tumor found in adults, and has ashort median survival time (MST). GBM is a heterogeneous group of brain tumors, is highly prone todevelop resistance and likely to recur. In the context of GBM, the delivery of anti-cancer drugs ischallenging because the blood brain barrier (BBB) restricts the passage of small molecules. Currently,nanomedicines based on liposomes, micelles, polymeric nanoparticles, and microparticles have attractedmuch attention, because they can cross the BBB and deliver anti-cancer drugs specifically to brain tumors. In this context, hydrogel-based systems incorporating nanoparticles, implantable carmustine wafers,microspheres, and lipid-based nanoparticles now appear to offer more effective, safer treatmentstrategies than conventional chemotherapeutic regimens. This review describes different polymerichydrogel, chitosan, dendrimers, wafers, microspheres, and lipid-based nanoparticles like liposomes andsolid-lipid nanoparticles that offers prominent strategies for the treatment and diagnosis of GBM.
Asmita Banstola,Fakhrossadat Emami,정지헌,육심명 한국고분자학회 2018 Macromolecular Research Vol.26 No.11
Pancreatic cancer is an extremely heterogeneous, malignant disease with a complicated tumor microenvironment and a dismal prognosis. Extensive stroma surrounding the cancer and the sequestering of chemotherapeutic agents play dominant roles in tumor growth and metastasis and in suppressing the delivery of cytotoxic drugs to tumor cells. Currently, nanoscience is in the forefront of developments aimed at devising novel techniques to treat tumors. Gold nanoparticles (GNPs) are often used as potential imaging and therapeutic agents for cancers, since they offer: (1) Passive targeting because of better permeation and retention effects, (2) photothermal effects caused by efficient light-to-heat conversion, and (3) the potential to use simple gold-thiol bioconjugation chemistry to conjugate desired molecules for targeted drug delivery. Together, these benefits can increase the therapeutic success of GNPs when used in combination with conventional treatment strategies, such as surgery, chemotherapy, or radiotherapy. In this review, we discuss current trends in GNP research in the field of pancreatic cancer theranostics.
Tung Thanh Pham,Hanh Thuy Nguyen,Cao Dai Phung,Shiva Pathak,Shobha Regmi,하동호,김종오,용철순,김상균,최지은,육심명,박준범,정지헌 한국공업화학회 2019 Journal of Industrial and Engineering Chemistry Vol.76 No.-
Selective delivery of anti-cancer drugs to bone tumors remains an on-going developmental issue due toproblems of drug availability and the physiological nature of bone. This study was undertaken to enhanceaccumulation of doxorubicin (DOX) in bone metastasis microenvironments using alendronate-functionalized graphene oxide nanosheets (NGO-ALs). In vivo biodistribution study showed NGO-ALswere retained for longer and at higher concentrations in bone tumor areas than non-functionalizedNGOs. Ourfindings suggest that NGO-ALs could be used as a promising carrier to enhance antitumoreffects and diminish the off-target effects of DOX for the treatment of bone metastasis.