Yu-Kyoung Oh

Seoul National University, Sŏul, Seoul, South Korea

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Publications (131)546.8 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Here, we report the pharmacokinetics and in vivo fate of intra-articularly transplanted human mesenchymal stem cells in comparison with those of intravenoulys administered cells. Bone marrow-derived human clonal mesenchymal stem cells (hcMSC) were transplanted to nude mice via intravenous or intra-articular routes. The numbers of hcMSC in blood and tissue samples were measured by quantitative real time-polymerase chain reaction (qPCR) with human Alu as a detection marker. Following intra-articular transplantation, the blood levels of hcMSC peaked 8 h post dose and gradually diminished, showing a 95-fold higher mean residence time than hcMSC delivered via the intravenous route. Unlike intravenously administered hcMSC, intra-articularly injected hcMSC were mainly retained at injection joint sites, where their levels 8 h post-dose were 116-fold higher than those in muscle tissues. Regardless of injection routes, biodistribution patterns did not significantly differ between normal and osteoarthritis-induced mice. Quantitiave analysis using hAlu-specific qPCR revealed that hcMSC levels in joint tissues were significantly higher than those in muscle tissues 120 d post dose. These dramatic differences in kinetic behavior, and fate of intra-articularly transplanted hcMSC compared with intravenously administered hcMSC may provide insights useful for the development of human mesenchymal stem cells for arthritis therapeutics.
    Stem Cells and Development 12/2014; · 4.20 Impact Factor
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    ABSTRACT: Here, we report reduced graphene oxide (rGO) nanosheets coated with an anti-angiogenic anticancer taurocholate derivative of low-molecular-weight heparin (LHT7) as a tumor-targeting nanodelivery platform for anticancer drugs. Surface coating of LHT7 onto rGO was confirmed using fluorescein isothiocyanate-labeled LHT7, monitored as fluorescence quenching due to associated rGO. Unlike plain rGO, LHT7-coated rGO (LHT-rGO) nanosheets maintained a stable dispersion under physiological conditions for at least 24h. Moreover, LHT-rGO provided greater loading capacity for doxorubicin (Dox) compared with uncoated rGO nanosheets. Following intravenous administration into KB tumor-bearing mice, in vivo tumor accumulation of LHT-rGO/Dox was 7-fold higher than that of rGO/Dox 24h post dosing. In tumor tissues, LHT-rGO/Dox was shown to localize not to the tumor vasculature, but rather to tumor cells. Intravenously administered LHT-rGO/Dox showed the greatest anti-tumor effect in KB-bearing mice, reducing tumor volume by 92.5%±3.1% compared to the untreated group 25days after tumor inoculation. TUNEL assays revealed that the population of apoptotic cells was highest in the group treated with LHT-rGO/Dox. Taken together, our results demonstrate that LHT-rGO nanosheets confer improved dispersion stability, tumor distribution and in vivo antitumor effects, and may be further developed as a potential active nanoplatform of various anticancer drugs.
    Journal of Controlled Release 06/2014; · 7.26 Impact Factor
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    ABSTRACT: Despite the progress of conventional vaccines, improvements are clearly required due to concerns about the weak immunogenicity of these vaccines, intrinsic instability in vivo, toxicity, and the need for multiple administrations. To overcome such problems, nanotechnology platforms have recently been incorporated into vaccine development. Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses. This advantage is attributable to the nanoscale particle size, which facilitates uptake by phagocytic cells, the gut-associated lymphoid tissue, and the mucosa-associated lymphoid tissue, leading to efficient antigen recognition and presentation. Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors, thereby stimulating specific and selective immune responses. In this review, we introduce recent advances in nanocarrier-based vaccine delivery systems, with a focus on the types of carriers, including liposomes, emulsions, polymer-based particles, and carbon-based nanomaterials. We describe the remaining challenges and possible breakthroughs, including the development of needle-free nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.
    Asian Journal of Pharmaceutical Sciences 06/2014;
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    ABSTRACT: Previously, we developed a non-replicating recombinant baculovirus coated with human endogenous retrovirus envelope protein (AcHERV) for enhanced cellular delivery of human papillomavirus (HPV) 16L1 DNA. Here, we report the immunogenicity of an AcHERV-based multivalent HPV nanovaccine in which the L1 segments of HPV 16, 18, and 58 genes were inserted into a single baculovirus genome of AcHERV. To test whether gene expression levels were affected by the order of HPV L1 gene insertion, we compared the efficacy of bivalent AcHERV vaccines with the HPV 16L1 gene inserted ahead of the 18L1 gene (AcHERV-HP16/18L1) with that of AcHERV with the HPV 18L1 gene inserted ahead of the 16L1 gene (AcHERV-HP18/16L1). Regardless of the order, the bivalent AcHERV DNA vaccines retained the immunogenicity of monovalent AcHERV-HP16L1 and AcHERV-HP18L1 DNA vaccines. Moreover, the immunogenicity of bivalent AcHERV-HP16/18L1 was not significantly different from that of AcHERV-HP18/16L1. In challenge tests, both bivalent vaccines provided complete protection against HPV 16 and 18 pseudotype viruses. Extending these results, we found that a trivalent AcHERV nanovaccine encoding HPV 16L1, 18L1, and 58L1 genes (AcHERV-HP16/18/58L1) provided high levels of humoral and cellular immunogenicity against all three subtypes. Moreover, mice immunized with the trivalent AcHERV-based nanovaccine were protected from challenge with HPV 16, 18, and 58 pseudotype viruses. These results suggest that trivalent AcHERV-HPV16/18/58L1 could serve as a potential prophylactic baculoviral nanovaccine against concurrent infection with HPV 16, 18, and 58.
    PLoS ONE 04/2014; 9(4):e95961. · 3.53 Impact Factor
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    ABSTRACT: Anticancer chemotherapy usually involves the administration of several anticancer drugs that differ in their action mechanisms. Here, we aimed to test whether the combination of omacetaxine mepesuccinate (OMT) and doxorubicin (DOX) could show synergism, and whether the liposomal co-delivery of these two drugs could enhance their antitumor effects in cervical carcinoma model. OMT-loaded liposomes (OL) were prepared by loading the drug in the lipid bilayers. OL were then electrostatically complexed with DOX, yielding double-loaded liposomes (DOL). DOX-loaded liposomes (DL) were formulated by electrostatic interaction with negatively charged empty liposomes (EL). The combination index (CI) values were calculated to evaluate the synergism of two drugs. In vitro antitumor effects against HeLa cells were measured using CCK-8, calcein staining, and crystal violet staining. In vivo antitumor effects of various liposomes were tested using HeLa cell-bearing mice. Combination of DOX and OMT had ratio-dependent synergistic activities, with very strong synergism observed at a molar ratio of 4:1 (DOX:OMT). The sizes of EL, DL, OL, and DOL did not significantly differ, but the zeta potentials of DL and DOL were slightly higher than those of OL and EL. In vitro, DOL showed higher antitumor activity than OL, DL or EL in cervical carcinoma HeLa cells. In vivo, unlike other liposomes, DOL reduced the tumor growths by 98.6% and 97.3% relative to the untreated control on day 15 and 25 after the cessation of treatment, respectively. These results suggest that liposomal co-delivery of DOX and OMT could synergistically potentiate antitumor effects.
    Pharmaceutical Research 02/2014; · 4.74 Impact Factor
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    ABSTRACT: Here, we report the effect of structure on the biological properties of photoresponsive carbon nanomaterials. Poloxamer 407-functionalized single-walled carbon nanotubes (PSWCNT) and poloxamer 407-functionalized graphene nanosheets (PGNS) exhibited similar physical stability and heating capacities after irradiation with an 808 nm near-infrared (NIR) laser. Despite sharing common physical properties, the cellular uptake of the PSWCNT and PGNS differed significantly. Cancer cells treated with PGNS took up a higher quantity of the nanosheets than of the PSWCNT and displayed a higher rate of cancer cell killing upon laser irradiation. Structure of carbon nanomaterials also affected the in vivo behaviors. PGNS could circulate in the blood 2.2 times longer than that of the PSWCNT. PGNS accumulated in the SCC tumor tissues to a greater degree than did PSWCNT over 7 days. NIR irradiation resulted in the complete ablation of tumor tissues in the PGNS-treated group but not in the other groups. After NIR irradiation, 100% of the PGNS-treated and NIR-irradiated mice survived until day 70. These results suggest the importance of structure in controlling the in vivo behaviors of carbon nanomaterials. Moreover, the results indicate the structural advantages of nanosheets over nanotubes in the enhancement of photothermal anticancer effects.
    Biomaterials 02/2014; · 8.31 Impact Factor
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    ABSTRACT: Graphene-based nanosheets (GNS) are atomic-thickness monolayers of hexagonally arranged, graphite-derived carbon atoms that may be composed of graphene, graphene oxide, or reduced graphene oxide. They have attracted tremendous interest for their potential in pharmaceutical applications, due to their unique physical, chemical, and mechanical properties GNS exhibit highly uniform surface areas and may have hydroxyl (-OH), epoxide (-O-), and carboxyl functional groups at their basal surfaces and plane edges, depending on their oxidized and reduced surface properties. GNS show high-level optical absorption of near-infrared (NIR) light and elevate the temperature of nearby environments. Furthermore, they can be loaded with anticancer drugs via hydrophobic interactions, stacking, or electrostatic binding. Given these properties, GNS can be used in chemotherapy, photodynamic therapy, photothermal therapy, and theranostics. However, although GNS appear to have far-reaching potential in the field of biomedical research, their widespread pharmaceutical application has been limited by issues such as poor stability in physiological buffers, undefined mechanisms of cellular uptake, toxicity problems, and a lack of standard preparation methods. Here, we review the current pharmaceutical applications of GNS, focusing on chemotherapy, phototherapy, combo therapy and theranostic applications with challenging issues.
    Current pharmaceutical biotechnology 01/2014; · 3.40 Impact Factor
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    ABSTRACT: Here, we report a double-stranded, dual-anchored, fluorescent aptamer on reduced graphene oxide (rGO) for the sensitive, selective, and speedy detection of a target protein in biological samples. This nano detector is composed of a target protein-specific fluorescent aptamer with BHQ1 as one anchoring moiety that forms double-stranded sequences with a complementary oligonucleotide sequence with BHQ1 as the other anchoring moiety, anchored to rGO nanosheets. The double-stranded and dual-anchored aptamer on rGO nanosheets (DAGO) exhibited 7.3-fold higher fluorescence intensities compared to a single-stranded, single-anchored fluorescent aptamer on rGO. As a model target protein, interferon-γ was used. DAGO detected the target protein, with linearity over a five-orders-of-magnitude concentration range (0.1 ng/ml-10 μg/ml) in buffer and human serum. DAGO was highly specific for the target protein, exhibiting little changes in fluorescence intensity in response to the non-target proteins, interleukin-2 and tumor necrosis factor-α. Moreover, DAGO allowed rapid quantification of the target protein in human immunodeficiency virus-positive patient serum samples. DAGO-based detection was complete in less than 10 min. Our results indicate that the DAGO provides new opportunities for the rapid and specific detection of target proteins in biological samples and could be widely applied to quantitate various target proteins by replacing the aptamer sequences.
    Biomaterials 01/2014; · 8.31 Impact Factor
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    ABSTRACT: Estimation of the efficacy of mosquito repellents requires both laboratory and field tests. The results of field tests are more meaningful, but the safety of volunteers in such tests may be a significant concern. In the current study, we compared tests of mosquito repellent efficacy under semifield conditions in an outdoor enclosure with those under laboratory and field conditions. In this study, we assessed the efficacy of N,N-diethyl-meta-toluamide under laboratory conditions with human volunteers and under semifield and field conditions with Centers for Disease Control and Prevention traps and experimental mice. A semifield test may be a suitable replacement for the more difficult field test for assessment of mosquito repellent efficacy. Semifield tests should be considered when developing new guidelines for testing.
    Journal of Medical Entomology 01/2014; 51(1):182-8. · 1.82 Impact Factor
  • Journal of Controlled Release 01/2014; 189:80–89. · 7.26 Impact Factor
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    ABSTRACT: Despite the advantages of DNA vaccines, overcoming their lower efficacy relative to that of conventional vaccines remains a challenge. Here, we constructed a human endogenous retrovirus (HERV) envelope-coated, nonreplicable, baculovirus-based HA vaccine against swine influenza A/California/04/2009(H1N1) hemagglutin (HA) (AcHERV-sH1N1-HA) as an alternative to conventional vaccines and evaluated its efficacy in two strains of mice, BALB/c and C57BL/6. A commercially available, killed virus vaccine was used as a positive control. Mice were intramuscularly administered AcHERV-sH1N1-HA or the commercial vaccine and subsequently given two booster injections. Compared with the commercial vaccine, AcHERV-sH1N1-HA induced significantly higher levels of cellular immune responses in both BALB/c and C57BL/6 mice. Unlike cellular immune responses, humoral immune responses depended on the strain of mice. Following immunization with AcHERV-sH1N1-HA, C57BL/6 mice showed HA-specific IgG titers 10- to 100-fold lower than those of BALB/c mice. In line with the different levels of humoral immune responses, the survival of immunized mice after intranasal challenge with sH1N1 virus (A/California/04/2009) depended on the strain. After challenge with 10-times the median lethal dose (MLD50) of sH1N1 virus, 100% of BALB/c mice immunized with the commercial vaccine or AcHERV-sH1N1-HA survived. In contrast, C57BL/6 mice immunized with AcHERV-sH1N1-HA or the commercial vaccine showed 60% and 70% survival respectively, after challenge with sH1N1 virus. In all mice, virus titers and results of histological analyses of lung tissues were consistent with the survival data. Our results indicate the importance of humoral immune response as a major defense system against influenza viral infection. Moreover, the complete survival of BALB/c mice immunized with AcHERV-sH1N1-HA after challenge with sH1N1 virus suggests the potential of baculoviral vector-based vaccines to achieve an efficacy comparable to that of killed virus vaccines.
    PLoS ONE 11/2013; 8(11):e80762. · 3.53 Impact Factor
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    ABSTRACT: We synthesized and evaluated (64)Cu-labeled tetraiodothyroacetic acid (tetrac)-conjugated liposomes for PET imaging of tumor angiogenesis, because tetrac inhibits angiogenesis via integrin αVβ3. Tetrac-PEG-DSPE and DOTA-PEG-DSPE were synthesized and formulated with other lipids into liposomes. The resulting tetrac/DOTA-liposomes were labeled with (64)Cu at 40 °C for 1 h and purified using a PD-10 column. (64)Cu-DOTA-liposomes were also prepared for comparison. Human aortic endothelial cell (HAEC) binding studies were performed by incubating the liposomes with the cells at 37 °C. MicroPET imaging followed by tissue distribution study was carried out using U87MG tumor-bearing mice injected with tetrac/(64)Cu-DOTA-liposomes or (64)Cu-DOTA-liposomes. HAEC binding studies exhibited that tetrac/(64)Cu-DOTA-liposomes were avidly taken up by the cells from 1.02 %ID at 1 h to 11.89 %ID at 24 h, while (64)Cu-DOTA-liposomes had low uptake from 0.47 %ID at 1 h to 1.57 %ID at 24 h. MicroPET imaging of mice injected with tetrac/(64)Cu-DOTA-liposomes showed high radioactivity accumulation in the liver and spleen. ROI analysis of the tumor images revealed 1.93±0.12 %ID/g at 1 h and 2.70±0.36 %ID/g at 22 h. In contrast, tumor ROI analysis of (64)Cu-DOTA-liposomes revealed 0.54±0.08 %ID/g at 1 h and 0.52±0.09 %ID/g at 22 h. Tissue distribution studies confirmed that the tumor uptakes of tetrac/(64)Cu-DOTA-liposomes and (64)Cu-DOTA-liposomes were 1.75±0.03 %ID/g and 0.36±0.01 %ID/g at 22 h, respectively. These results demonstrate that tetrac/(64)Cu-DOTA-liposomes have significantly enhanced tumor uptake compared to (64)Cu-DOTA-liposomes due to tetrac conjugation. Further studies are warranted to reduce the liver and spleen uptake of tetrac/(64)Cu-DOTA-liposomes.
    Nuclear Medicine and Biology 09/2013; · 2.41 Impact Factor
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    ABSTRACT: Here, we report hyaluronyl reduced graphene oxide (rGO) nanosheets as a tumor-targeting delivery system for anticancer agents. Hyaluronyl-modified rGO nanosheets were prepared by synthesizing cholesteryl hyaluronic acid (CHA) and using it to coat rGO nanosheets, yielding CHA-rGO. Compared with rGO, CHA-rGO nanosheets showed increased colloidal stability under physiological conditions and improved in vivo safety, with a survival rate of 100% after intravenous administration of 40 mg/kg in mice. The doxorubicin (Dox) loading capacity of CHA-rGO was 4-fold greater than that of rGO. Uptake of Dox by CD44-overexpressing KB cells was higher for CHA-rGO than for rGO, and was decreased in the presence of hyaluronic acid through competition for CD44 receptor binding. After intravenous administration in tumor-bearing mice, CHA-rGO/Dox showed higher tumor accumulation than rGO/Dox. The in vivo antitumor efficacy of Dox delivered by CHA-rGO was significantly increased compared with free Dox or rGO/Dox. In CHA-rGO/Dox-treated mice, tumor weights were reduced to 14.1% ± 0.1% of those in untreated mice. Our findings indicate that CHA-rGO nanosheets possess greater stability, safety, drug-loading capacity, and CD44-mediated delivery of Dox than rGO nanosheets. These beneficial properties of CHA-rGO improved the distribution of Dox to tumors and facilitated the cellular uptake of Dox by CD44-overexpressing tumor cells, resulting in enhanced anticancer effects.
    Biomaterials 09/2013; · 8.31 Impact Factor
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    ABSTRACT: A series of novel (1S)-(-)-verbenone derivatives was synthesized bearing a 4-styryl scaffold. The synthesized compounds were tested for their anti-oxidant, anti-excitotoxic, and anti-ischemic activities. These derivatives significantly reduced oxygen-glucose deprivation-induced neuronal injury and N-methyl-d-aspartic acid-evoked excitotoxicity in cortical neurons. Furthermore, compound 3f was identified as a potent anti-ischemic agent in an in vitro ischemic model, potentially due to the inhibition of N-methyl-d-aspartic acid-evoked excitotoxicity and oxidative/nitrosative stress.
    Bioorganic & medicinal chemistry letters 07/2013; · 2.65 Impact Factor
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    ABSTRACT: To improve the survival of transplanted human adipose-derived stem cells (ADSCs), a liposome preparation containing the apoptosome inhibitor, NS3694, was formulated and co-delivered with ADSCs in fibrin gel scaffolds. Liposomes provided enhanced effect on ADSC proliferation in vitro as compared to free drug. Exposure of ADSCs to liposomal NS3694 for 7 days did not affect the surface marker expression profile. NS3694 encapsulated in negatively charged liposomes composed of phosphatidylcholine, phosphatidylglycerol, and cholesterol was evaluated in vivo following subcutaneous transplantation in mice. Survival of ADSCs co-delivered with liposomal NS3694 was significantly higher than that of untreated ADSCs or ADSCs treated with free NS3694 or empty liposomes. An immunohistochemical analysis revealed a higher number of human nucleus-positive cells after treatment with liposomal NS3694 than following treatment with free NS3694. Similarly, liposomal NS3694 significantly enhanced survival of transplanted ADSCs in rabbits compared to other treatments. Taken together, our results indicate the potential of liposomal NS3694 co-delivered with ADSCs using fibrin gel systems as an in vivo-survival enhancer.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2013; · 3.15 Impact Factor
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    ABSTRACT: The main purpose of this study was to investigate the potential of self-nano-emulsifying drug delivery system (SNEDDS) in improving the bioavailability of docetaxel (DCT) and its chemotherapeutic effect. The DCT-loaded SNEDDS was prepared by employing rational blends of capryol 90, labrasol, and transcutol HP using ternary phase diagram. The liquid nano-emulsion was spray-dried into solid SNEDDS (D-SNEDDS) using an inert porous carrier, colloidal silica. The optimized formulation was characterized in terms of physico-chemical and pharmacokinetic parameters. Furthermore, anti-tumor efficacy of D-SNEDDS was compared with commercial marketed product, Taxotere(®). The various composition of SNEDDS were screened and found optimal at a volume ratio of 10/75/15 for capryol 90, labrasol, and transcutol HP, respectively. We observed a high oral bioavailability of 17% DCT for D-SNEDDS than compared to only 2.6% for pure DCT solution. Notably, D-SNEDDS exhibited an augmented anti-tumor efficacy with a reduced toxicity profile when compared with intravenously administered Taxotere(®), the commercialized formulation of DCT. Taken together, D-SNEDDS could be a potential candidate for an oral dosage form of DCT with enhanced antitumor activity and reduced toxicity.
    International Journal of Pharmaceutics 05/2013; · 3.99 Impact Factor
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    ABSTRACT: PURPOSE: To investigate the potential of thermosensitive and biadhesive nanomicelles in improving the bioavailability of docetaxel (DCT) and its chemotherapeutic effect. METHOD: DCT-loaded nanomicelles were prepared by emulsufication and characterized in terms of physico-chemical and visco-elastic parameters. The optimzed formulation was evaluated for in vivo localization, pharmacokinetic and anti-tumor efficacy. RESULTS: The hydrodynamic size of DCT-loaded nanomicelles was approximately 13 nm and the nanomicelles exhibited a sufficient gelation strength (9250 mPa·s) and bioadhesive force (2100 dyn/cm(2)) to be retained in the upper part of rectum. We observed a high rectal bioavailability of 29% DCT compared to that following oral administration in rats, as it successfully evaded the multidrug efflux transporters and hepatic first-pass metabolism. Plasma concentration around ∼50 ng/mL was maintained throughout the study period (12 h) while Taxotere® attained subtherapeutic range within 4 h of drug administration. Results also revealed that the rectally administered DCT-loaded nanomicelles exhibited a significant anti-tumor effect (200 mm(3)) with a reduced toxicity profile when compared to orally administered DCT (950 mm(3)). Furthermore, histological study showed that the rectal mucosa was completely intact with no signs of irritation upon treatment with DCT-loaded nanomicelles. CONCLUSIONS: Taken together, our novel thermosensitive and biadhesive nanomicelles demonstrated the ability to improve the bioavailability and chemotherapeutic potential of DCT in vivo. To the best of our knowledge, this is the first report describing the rectal delivery of DCT-loaded nanomicelles.
    Pharmaceutical Research 04/2013; · 4.74 Impact Factor
  • Asian Journal of Pharmaceutical Sciences 04/2013; 8(2):72-80.
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    ABSTRACT: Here, we report a cationic nanolipoplex as a pulmonary cellular delivery system for small-interfering RNA (siRNA). Six nanoliposomes differing in cationic lipids were formulated and screened in vitro and in vivo for cellular delivery functions in lung cells/tissues. Although the six nanoliposomes showed similar siRNA delivery efficiency in vitro, they exhibited significant differences in pulmonary cellular delivery functions in vivo. Among the various nanoliposomes, cationic dioleoyl-sn-glycero-3-ethylphosphocholine and cholesterol (ECL)-based nanoliposomes showed the highest pulmonary cellular delivery in vivo and the lowest cytotoxicity in vitro. The delivery efficiency of fluorescent siRNA in ECL nanoliposomes was 26.2-fold higher than that of naked siRNA in vivo. Treatment with Mcl1 (myeloid cell leukemia sequence 1)-specific siRNA (siMcl1) using ECL nanolipoplexes reduced target expression in B16F10 cell lines, whereas control, luciferase-specific siGL2 in ECL nanolipoplexes did not. In metastatic lung cancer mouse models induced by B16F10 or Lewis lung carcinoma (LLC) cells, intratracheal administration of siMcl1 in ECL nanolipoplexes significantly silenced Mcl1 mRNA and protein levels in lung tissue. Reduced formation of melanoma tumor nodules was observed in the lung. These results demonstrate the utility of ECL nanoliposomes for pulmonary delivery of therapeutic siRNA for the treatment of lung cancers and potentially for other respiratory diseases.Molecular Therapy (2013); doi:10.1038/mt.2013.10.
    Molecular Therapy 02/2013; · 6.43 Impact Factor
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    ABSTRACT: Here, we report the safety, tumor accumulation and potential of polyethylene glycol-grafted graphene oxide (pGO) as a multimodal nanocarrier of photosensitizers and synergistic anticancer agents. First, both graphene oxide (GO) and pGO were synthesized, and their in vitro and in vivo toxicities were tested. When 80 mg/kg was injected intravenously into mice, there was 100% fatality in the GO-treated group, but 100% survival among mice treated with pGO nanosheets. Treatment of cells with a photosensitizer chlorin e6 (Ce6) in pGO nanophysisorplexes significantly enhanced cellular delivery compared to that seen with Ce6 alone. The combination and dose reduction indexes revealed that combining doxorubicin (Dox) with Ce6 with at a molar ratio of 1:2 provided the highest synergism. The Ce6- and Dox-loaded pGO nanophysisorplexes (Ce6/Dox/pGO) were 148.0 ± 18.0 nm in size. Molecular imaging of mice showed that Ce6/Dox/pGO could accumulate in tumor tissues over 3 days. Moreover, in SCC tumor-bearing mice, the photodynamic anticancer effects of Ce6/Dox/pGO were higher than those of Ce6/pGO or Dox/pGO. Moreover, tumor sections from illuminated mice treated with Ce6/Dox/pGO showed substantial disruption of tumor nuclei, whereas the other groups did not. Our results suggest that pGO nanosheets have superior in vivo safety relative to GO, and that it is possible to enhance the tumor tissue distribution and photodynamic anticancer effects of systemically administered Ce6 by forming multimodal nanophysisorplexes with pGO and synergistic anticancer chemotherapeutics such as Dox.
    Biomaterials 02/2013; · 8.31 Impact Factor

Publication Stats

2k Citations
546.80 Total Impact Points


  • 1998–2014
    • Seoul National University
      • • Research Institute of Pharmaceutical Sciences
      • • College of Pharmacy
      Sŏul, Seoul, South Korea
  • 2009–2013
    • Konkuk University
      • • Department of Animal Biotechnology
      • • College of Animal Bioscience and Technology
      Sŏul, Seoul, South Korea
  • 2005–2013
    • Yeungnam University
      • College of Pharmacy
      Asan, South Chungcheong, South Korea
  • 2006–2012
    • Korea University
      Sŏul, Seoul, South Korea
  • 2010–2011
    • Kyungpook National University
      • • School of Medicine
      • • Department of Biochemistry and Cell Biology
      Sangju, North Gyeongsang, South Korea
  • 2009–2010
    • Korea Institute of Science and Technology
      • Biomedical Research Institute
      Sŏul, Seoul, South Korea
  • 2008
    • Sungkyunkwan University
      • School of Pharmacy
      Sŏul, Seoul, South Korea
  • 2007
    • Korea Advanced Institute of Science and Technology
      • Department of Biological Sciences
      Seoul, Seoul, South Korea
    • The Seoul Institute
      Sŏul, Seoul, South Korea
  • 2003–2007
    • Hanyang University Medical Center
      Sŏul, Seoul, South Korea
  • 2001–2007
    • CHA University
      • • Graduate School of Life Science and Biotechnology
      • • College of Medicine
      Seoul, Seoul, South Korea
  • 2002–2006
    • Ewha Womans University
      Sŏul, Seoul, South Korea