Rhamnolipid nanoparticles for <i>in vivo</i> drug delivery and photodynamic therapy

Yi, Gawon,Son, Jihwan,Yoo, Jihye,Park, Changhee,Koo, Heebeom 1637.934400 2019 NANOMEDICINE Vol.19 No.-

<P><B>Abstract</B></P> <P>Herein, we report the development of self-assembled nanoparticles using rhamnolipid, a biosurfactant. Rhamnolipid is produced by <I>Pseudomonas aeruginosa</I>, and has an amphiphilic structure that is suitable for the formation of a nanoparticle shell. These rhamnolipid nanoparticles were loaded with pheophorbide a (Pba), a hydrophobic photosensitizer. The resulting nanoparticles had about 136.1-nm-diameter spherical shapes and had excellent water solubility without aggregation for one month. These nanoparticles showed fast uptake into SCC7 tumor cells and induced photodynamic damage upon laser irradiation. After intravenous injection to SCC7 tumor-bearing mice, their long blood circulation time and high accumulation in tumor tissue were observed in real-time fluorescence imaging. Upon laser irradiation, these rhamnolipid nanoparticles showed complete tumor suppression by photodynamic therapy <I>in vivo</I>. These promising results demonstrate the potential of rhamnolipid nanoparticles for drug delivery, and suggest that further attention to rhamnolipid research would be fruitful.</P> <P><B>Graphical Abstract</B></P> <P>New self-assembled nanoparticles were developed using rhamnolipid, a biosurfactant which is produced by <I>Pseudomonas aeruginosa</I>. Pheophorbide a (Pba), a hydrophobic photosensitizer was loaded into the nanoparticles. Their diameter was about 136.1 nm, and they had excellent water solubility without aggregation for one month. These nanoparticles showed fast uptake into tumor cells. After intravenous injection to SCC7 tumor-bearing mice, their long blood circulation time and high accumulation in tumor tissue were observed in real-time fluorescence imaging. Upon laser irradiation, they showed complete tumor suppression by photodynamic therapy <I>in vivo</I>. On the basis of these results, we expect that more applications for rhamnolipid nanoparticles will be explored in the future.</P> <P>[DISPLAY OMISSION]</P>

Application of click chemistry in nanoparticle modification and its targeted delivery

Gawon Yi,Jihwan Son,Jihye Yoo,Changhee Park,구희범 한국생체재료학회 2018 생체재료학회지 Vol.22 No.2

Background: Click chemistry is termed as a group of chemical reactions with favorable reaction rate and orthogonality. Recently, click chemistry is paving the way for novel innovations in biomedical science, and nanoparticle research is a representative example where click chemistry showed its promising potential. Challenging trials with nanoparticles has been reported based on click chemistry including copper-catalyzed cycloaddition, strain-promoted azide-alkyne cycloaddition, and inverse-demand Diels-Alder reaction. Main body: Herein, we provide an update on recent application of click chemistry in nanoparticle research, particularly nanoparticle modification and its targeted delivery. In nanoparticle modification, click chemistry has been generally used to modify biological ligands after synthesizing nanoparticles without changing the function of nanoparticles. Also, click chemistry in vivo can enhance targeting ability of nanoparticles to disease site. Conclusion: These applications in nanoparticle research were hard or impossible in case of traditional chemical reactions and demonstrating the great utility of click chemistry.

Early Intervention Reduces the Spread of COVID-19 in Long-Term Care Facilities in the Republic of Korea

Park Shin Young,Choi Gawon,Lee Hyeyoung,Kim Na-young,Lee Seon-young,Kim Kyungnam,Shin Soyoung,Jang Eunsu,Moon YoungSin,Oh KwangHwan,Choi JaeRin,Lee Sang-Eun,Kim Young-Man,Kim Jieun,Yi Seonju,Gwack Jin 질병관리본부 2020 Osong Public Health and Research Persptectives Vol.11 No.4

This study describes the epidemiological characteristics of coronavirus disease 2019 (COVID-19) based on reported cases from long-term care facilities. As of April 20th, 2020, 3 long-term care facilities in a metropolitan area of South Korea had reported cases of COVID-19. These facilities’ employees were presumed to be the sources of infection. There were 2 nursing hospitals that did not report any additional cases. One nursing home had a total of 25 cases, with an attack rate of 51.4% (95% CI 35.6–67.0), and a fatality rate of 38.9% (95% CI 20.3–61.4) among residents. The results from this study suggest that early detection and maintenance of infection control minimizes the risk of rapid transmission.

Folate-modified PLGA nanoparticles for tumor-targeted delivery of pheophorbide a <i>in vivo</i>

Son, Jihwan,Yang, Seung Mok,Yi, Gawon,Roh, Yoon Jin,Park, Hyeji,Park, Jae Myung,Choi, Myung-Gyu,Koo, Heebeom Elsevier 2018 Biochemical and biophysical research communication Vol.498 No.3

<P><B>Abstract</B></P> <P>Targeted drug delivery has been an important issue for tumor therapy including photodynamic therapy (PDT). The purpose of our study is to increase the targeting efficiency of photosensitizer (PS) using folate-modified nanoparticles (NPs) to tumor site <I>in vivo</I>. Folate receptor is over-expressed on the surface of many human cancer cells. We prepared poly (lactic-co-glycolic acid) (PLGA) NPs containing pheophorbide a (Pba), a PS that is used in PDT and generates free radical for killing cancer cells. The surface of NPs was composed of phospholipids modified with polyethylene glycol (PEG) and folate (FA). The size of the resulting FA-PLGA-Pba NPs was about 200 nm in PBS at pH 7.4 and they were stable for long time. They showed faster cellular uptake to MKN28 human gastric cancer cell line than control PLGA-Pba NPs by high-affinity binding with folate receptors on cell surface. In MTT assay, FA-PLGA-Pba NPs also showed enhanced tumor cell killing compared to control PLGA-Pba NPs. <I>In vivo</I> and <I>ex vivo</I> imaging showed high accumulation of FA-PLGA-Pba NPs in tumor site during 24 h after intravenous injection to MKN28 tumor-bearing mice model. These results demonstrate that our FA-PLGA-Pba NPs are useful for tumor-targeted delivery of PS for cancer treatment by PDT.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Folate-modified PLGA nanoparticles (FA-PLGA-Pba NPs) were developed with non-toxic materials. </LI> <LI> FA-PLGA-Pba NPs were stable in aqueous condition for long time without aggregation. </LI> <LI> FA-PLGA-Pba NPs killed cancer cells effectively upon laser irradiation, and showed superior tumor-targeting <I>invivo</I>. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

The effects of doxorubicin-loaded liposomes on viability, stem cell surface marker expression and secretion of vascular endothelial growth factor of three-dimensional stem cell spheroids

Lee, Hyunjin,Son, Jihwan,Na, Chae-Bin,Yi, Gawon,Koo, Heebeom,Park, Jun-Beom D.A. Spandidos 2018 Experimental and therapeutic medicine Vol.15 No.6

<P>The aim of the present study was to evaluate the effects of anionic, cationic and neutral liposomes containing doxorubicin on the cellular viability and osteogenic differentiation of three-dimensional stem cell spheroids. Doxorubicin-loaded liposomes were prepared using the traditional thin-lipid-film-hydration method and were characterized using transmission electron microscopy and a zeta potential analyzer. The doxorubicin release profile from these liposomes was also analyzed <I>in vitro</I>. Three-dimensional cell spheroids were fabricated using silicon elastomer-based concave microwells. Qualitative results of cellular viability were observed using a confocal microscope and quantitative cellular viability was evaluated using a Cell-Counting Kit-8 (CCK-8) assay. Furthermore, the secretion of vascular endothelial growth factor was evaluated. Western blot analysis was performed to assess the expression of collagen I and glyceraldehyde 3-phosphate. Results indicated that the spheroids were well formed in silicon elastomer-based concave microwells on day 1. In general, the shapes of the cells in the in the doxorubicin-loaded anionic, cationic and neutral liposome groups were similar to the control group except for the 10 µg/ml groups on days 3, 5, and 7. No significant changes in cellular viability were noted with the addition of doxorubicin at day 1 but significant decreases in cellular viability were noted with application of doxorubicin at day 5. Notably, higher concentrations of doxorubicin reduced the secretion of vascular endothelial growth factor and stem cell marker expression. To conclude, the present study indicated that doxorubicin-loaded anionic liposomes produced the most sustained release profile and cationic liposomes produced the highest uptake of the stem cell spheroids. These findings suggested that higher concentrations of doxorubicin-loaded liposomes affected cellular viability, the secretion of vascular endothelial growth factor and stem cell marker expression.</P>