Enhanced anticancer activity and intracellular uptake of paclitaxel-containing solid lipid nanoparticles in multidrug-resistant breast cancer cells

Xu, Wenting,Bae, Eun Ju,Lee, Mi-Kyung Dove Medical Press 2018 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.13 No.-

<P><B>Purpose</B></P><P>The aim of this study was to show enhanced anticancer activity of paclitaxel (Ptx) incorporated into solid lipid nanoparticles (SLNs) and reveal reversal of multidrug resistance (MDR) by SLNs mediated by increased uptake through different entry mechanisms from that in drug-sensitive cells.</P><P><B>Methods</B></P><P>Anticancer activity of Ptx incorporated in SLNs (Ptx-SLNs) was measured in the drug-sensitive human breast cancer cell line MCF7 and its MDR variant MCF7/ADR. Cellular uptake of cargo molecules in SLNs was compared using Ptx-SLNs and rhodamine 123-loaded SLNs (Rho-SLNs) in both cell lines. In addition, endocytic uptake was evaluated using genistein (Gen) and chlorpromazine (Cpz) as inhibitors of clathrin- and caveola-mediated endocytosis, respectively.</P><P><B>Results</B></P><P>Ptx-SLNs showed remarkably enhanced anticancer activity in MCF7/ADR compared to Ptx delivered in dimethyl sulfoxide (DMSO) and Cremophor EL-based vehicles. SLNs significantly increased intracellular uptake of Ptx and Rho in MCF7/ADR. Western blotting demonstrated that clathrin was expressed in both cell lines, while caveolin 1 was expressed only in MCF7/ADR. In MCF7/ADR, uptake of Ptx-SLNs and Rho-SLNs was reduced by Gen, while there was no change by Cpz, suggesting the involvement of caveola-mediated endocytosis. Size reduction of Rho-SLNs through high-pressure homogenization (Rho-SLNs) appeared to cause a shift of the endocytosis mechanism from a clathrin-independent pathway to a clathrin-dependent one. In contrast to MCF7/ADR, the uptake of SLNs into MCF7 was not changed by Gen or Cpz, suggesting involvement of clathrin- and caveola-independent mechanism for the entry of SLNs.</P><P><B>Conclusion</B></P><P>MDR was reversed by incorporating drug into SLNs, and the reversal was mediated by increased uptake of SLNs evading efflux pumps in MDR cells. The enhanced uptake could also be due to the use of different endocytosis pathways by SLNs in MDR cells from drug-sensitive cancer cells.</P>

Cellular uptake and antitumour activity of paclitaxel incorporated into trilaurin-based solid lipid nanoparticles in ovarian cancer

Xu, Wenting,Lim, Soo-Jeong,Lee, Mi-Kyung Informa UK, Ltd. 2013 Journal of microencapsulation Vol.30 No.8

<P>Trilaurin-based solid lipid nanoparticles (TL-SLNs) containing paclitaxel (PTX) were prepared by hot-melt high-pressure homogenisation and subsequent freezing and thawing. PTX-containing TL-SLNs showed 160.0 ± 15.8 nm of mean particle size and −43.9 mV of zeta potential. Scanning electron microscopy also revealed the spherical shape and submicron-size of the TL-SLNs. Differential scanning calorimetry measurement presented melting transition peak of TL in SLNs indicating the solidified state of the core lipid. The prepared TL-SLNs were physically stable without significant particle size changes at 4 °C for 2 months. The amounts of uptake into the human ovarian cancer cells, SKOV-3, were similar between PTX delivered in Cremophor EL-based formulation and TL-SLNs. <I>In vitro</I> and <I>in vivo</I> antitumour activity of PTX in TL-SLNs was comparable to the commercial Cremophor EL-based formulation in SKOV-3. These results suggest that PTX-loaded TL-SLNs have promising potential as an alternative parenteral formulation for PTX.</P>

Development and evaluation of lipid nanoparticles for paclitaxel delivery: a comparison between solid lipid nanoparticles and nanostructured lipid carriers

Wenting Xu,이미경 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.7

Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were prepared as delivery system for water-insoluble anticancer agent, paclitaxel (PTX). The dispersion of SLNs was consisted of 5 % w/w tristearin, 3.75 % w/w egg phosphatidylcholine (egg PC) and 1 % w/w polysorbate 80 in water. NLCs were prepared using the same composition as SLNs except that 10 % of the solid lipid was replaced by triolein. PTX was incorporated into SLNs and NLCs to attain 0.025 % w/w in the dispersion. The particle size of the prepared SLNs and NLCs were 167.9 ± 21.3 and 121.9 ± 28.3 nm, respectively, and slightly increased to 239.1 ± 32.6 and 183.6 ± 36.2 nm by PTX incorporation. PTX incorporation also increased polydispersity index suggesting broader size distribution compared to that for empty particles. SLNs and NLCs showed sustained release of PTX in cell culture media containing 10 % fetal bovine serum at 37 ˚C compared to the commercial micellar formulation consisted of Cremophor EL and ethanol. PTX in SLNs and NLCs showed comparable cytotoxicity to the commercial formulation and free PTX against human breast cancer cell line, MCF-7. On the contrary, PTX in SLNs and NLCs showed higher anticancer activity against multidrug resistant (MDR) cancer cell line, MCF-7/ADR, compared to the free PTX delivered in DMSO, which indicates that both SLNs and NLCs would be effective carriers to avoid efflux pump expressed in MDR cancer cells. In conclusion, the SLNs and NLCs prepared in the present study showed similar characteristics each other and both can be used as effective delivery system for PTX.

중국 외국산 화장품 소비자의 자아일치성과 기능일치성이 브랜드 태도, 재 구매의도 및 추천의도에 미치는 영향

서문정 ( Wenting Xu ),신영애 ( Young Ae Shin ),임달호 ( Dal Ho Lim ) 한국유통경영학회(구 한국유통정보학회) 2015 유통정보학회지 Vol.18 No.4

Purpose: This study examined the effect of self congruity and functional congruity toward foreign cosmetics brand attitude, repurchase intention, and recommendation intention for Chinese female consumers. This study also aimed to investigate how moderating effects of low- and high-cost brands affected. Research design, data, and methodology: Questionnaires were distributed to female consumers in their twenties to thirties who lived in Shandong Province (山東省) China and had purchased foreign cosmetics. A total of 272 responses were collected, and then 243 responses were used for the final analysis. In order to test the hypothesis, regression analysis was performed using SPSS 18.0. Results: According to the research results, self congruity and functional congruity had a positive effect on brand attitude, and brand attitude positively affected repurchase intention and recommendation intention. This study tested the moderating effect of low- and high-cost brands. The results showed that low- and high-cost brands had no moderating effect on the impact that self congruity and functional congruity had on brand attitude. Conclusions: Companies are required to precede efforts to enhance self congruity and functional congruity by segmentalizing consumers rather than prices. There is need to fully analyze images preferred by consumers. If strategies such as various marketing advertising and sales promotion activities capable of emphasizing functional congruity such as design, quality, and function are developed, it will work as an effective marketing strategy to have positive feelings toward the brand.

Circ_0081143 Contributes to Gastric Cancer Malignant Development and Doxorubicin Resistance by Elevating the Expression of YES1 by Targeting mziR-129-2-3p

( Wenting Ou ),( Lin Lin ),( Rihong Chen ),( Qingwen Xu ),( Caijin Zhou ) 대한소화기기능성질환·운동학회 2022 Gut and Liver Vol.16 No.6

Background/Aims: The increased mortality of gastric cancer (GC) is mainly attributed to the development of chemoresistance. Circular RNAs, as the novel type of biomarkers in GC, have attracted wide attention. The purpose of this study was to investigate the functional role of circ_0081143 in GC with doxorubicin (DR) resistance and its potential action mechanism. Methods: The expression of circ_0081143, miR-129-2-3p and YES proto-oncogene 1 (YES1) in GC tissues and cells was measured by quantitative real-time polymerase chain reaction. The half maximal inhibitory concentration value was calculated based on the MTT cell viability assay. Cell proliferation and apoptosis were monitored by MTT and flow cytometry assays. Transwell assays were employed to check cell migration and invasion. The protein levels of YES1 and apoptosis-related proteins were detected by western blotting. The interaction between miR-129-2-3p and circ_0081143 or YES1 was verified by dual-luciferase reporter and pull-down assays. A tumorigenicity assay was conducted to verify the role of circ_0081143 in vivo. Results: Circ_0081143 was highly expressed in DR-resistant GC tumor tissues and cells. Depletion of circ_0081143 reduced DR resistance and inhibited DR-resistant GC cell proliferation, migration and invasion. Circ_0081143 targeted miR-129-2-3p and inhibited the role of miR-129-2-3p. In addition, YES1 was a target of miR-129-2-3p, and its function was suppressed by miR-129-2-3p. Importantly, circ_0081143 positively modulated the expression of YES1 through mediating miR-129-2-3p. Circ_0081143 knockdown weakened the DR-resistant GC tumor growth in vivo. Conclusions: Circ_0081143 knockdown weakened DR resistance and blocked the development of DR-resistant GC by regulating the miR-129-2-3p/YES1 axis. Our data suggest that circ_0081143 is a promising target for the treatment of GC with DR resistance. (Gut Liver 2022;16:861-874)

Combination of Curcumin and Paclitaxel-loaded Solid Lipid Nanoparticles to Overcome Multidrug Resistance

Li, Rihua,Xu, Wenting,Eun, Jae-Soon,Lee, Mi-Kyung The Korean Society of Pharmaceutical Sciences and 2011 Journal of Pharmaceutical Investigation Vol.41 No.6

Multi-drug resistance (MDR) has been known as a major hurdle in cancer chemotherapy. One of the most clinically significant causes of MDR was the efflux of anticancer agents mediated by p-glycoprotein (p-gp) over-expressed in MDR cancer cells. To overcome MDR, there have been several strategies such as co-administration with p-gp inhibitors and encapsulation of anticancer drugs into drug delivery systems. In the present study, curcumin was evaluated for its potential as p-gp inhibitor and MDR reversal activity when combined with paclitaxel incorporated into lipid nanoparticles (PTX/LN). Western blot assay showed curcumin did not modulate the level of p-gp expression in MCF-7/ADR which is a MDR variant of human breast cancer cell line, MCF-7, and over-expresses p-gp. However, curcumin inhibited p-gp-mediated efflux of calcein in a dose-dependent manner even though it showed lower activity compared to verapamil, a well-known p-gp inhibitor. Incorporation of paclitaxel into lipid nanoparticles partially recovered the anticancer activity of paclitaxel in MCF-7/ADR. The combined use of curcumin and PTX/LN exhibited further full reversal of MDR, suggesting susceptibility of PTX/LN to the efflux system. In conclusion, combined approach of using p-gp inhibitors and incorporation of the anticancer agents into nano-delivery systems would be an efficient strategy to overcome MDR.

Study on the Phase and Bath Electrochemical Properties in Electrodeposition of ZnS Film

Kegao Liu,Wenting Song,Yong Xu,Jing Li,Zhigang Wang 한양대학교 세라믹연구소 2018 Journal of Ceramic Processing Research Vol.19 No.2

ZnS does nearly not absorb sun light, it is the most suitable buffer layer material in solar cell. For preparing ZnS film withlow cost, the bath electrochemical performance and the effect of deposition potential on the phase of ZnS films prepared byelectrodeposition were studied under different electrodeposition conditions. The phases and morphology of product films wereinvestigated by X-ray diffraction and scanning electron microscope respectively. Experimental results show that, it was moreconducive to achieve co-deposition using the constant potential method. Compared with thiourea, it is easier to achieve codepositionfor ZnS. ZnS phase can be obtained under −1.0 ~ −1.6 V. When the deposition potential increased, the (100) crystalplane of the highest XRD peak of ZnS phase changed as (101) crystal plane. Well crystallized, dense and uniform ZnS filmcan be obtained under conditions of sodium citrate as complexing agent, sodium thiosulfate as sulfur source, ion ratio of Zincand Sulfide 1 : 5 and −1.2 V.

Interaction between rice bran albumin and epigallocatechin gallate and their physicochemical analysis

Rui Yang,Yuqian Liu,Jingjing Xu,Wenting Shang,Xiaoyuan Zhang,Yongjin Wang,Chris Blanchard,Zhongkai Zhou 한국식품과학회 2018 Food Science and Biotechnology Vol.27 No.6

Epigallocatechin gallate (EGCG) is sensitive to heat thus its application in food industry is limited. In this work, rice bran albumin protein (RAP) was used as a carrier for EGCG. RAP-EGCG complexes (RAPE) were prepared with the binding number n of 0.0505:1 (EGCG: RAP, w/w) and binding constant K of (0.74 ± 0.002) 9 104 M-1, which suggests that hydrogen bond/van der Waals forces played important roles in such binding. FTIR analysis demonstrated that EGCG could induce the secondary structure changes of RAP above the ratio of 1.92:1 (EGCG:RAP, w/w). Dynamic light scattering and scanning electron microscope results showed that EGCG could trigger RAP association. Furthermore, the EGCG stability in RAPE was significantly improved than that of free EGCG in 10–60 C. The antioxidant ability of EGCG in RAPE was partially retained. These findings prove that RAP is a potential carrier for polyphenols and is beneficial for mechanism investigation between protein and polyphenols.

Highly Sensitive Optical-fiber Humidity Sensor Based on Nafion-PVA Sol-gel

Ning Wang,Yuhao Li,Xiaolei Yin,Wenting Liu,Shiqi Liu,Liang Xu,Xuwei Zhao,Yanxi Zhong 한국광학회 2023 Current Optics and Photonics Vol.7 No.1

HOXD Antisense Growth-Associated Long Noncoding RNA Promotes Triple-Negative Breast Cancer Progression by Activating Wnt Signaling Pathway

Chenguang Zhang,Ying Yang,Lina Yi,Xuelaiti Paizula,Wenting Xu,Xiuping Wu 한국유방암학회 2021 Journal of breast cancer Vol.24 No.3

Purpose: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer owing to high heterogeneity, aggressive nature, and lack of treatment options, which has a substantial deleterious effect on patients' lives. HOXD antisense growth-associated long noncoding RNA (lncRNA) (HAGLR) plays tumor-promoting roles in many cancers. In this study, we aimed to explore the role of HAGLR in TNBC. Methods: Quantitative real-time polymerase chain reaction assays were used to examine the expression of RNAs. Functional experiments were conducted to test the biological behavior of TNBC cells. Moreover, MS2-RNA immunoprecipitation, luciferase reporter, and RNA pull-down assays were conducted to verify the binding relationship between HAGLR, microRNA-143-5p (miR-143-5p), and serine- and arginine-rich splicing factor 1 (SRSF1). Results: HAGLR was found to be highly expressed in TNBC tissues and cells, and inhibiting HAGLR suppressed cell proliferation, migration, and invasion and promoted cell apoptosis in TNBC. Meanwhile, miR-93-5p was shown to bind to HAGLR and SRSF1. In addition, SRSF1 plays an oncogenic role in TNBC. Importantly, HAGLR could activate the Wnt signaling pathway by sponging miR-93-5p to upregulate SRSF1; thus, accelerating TNBC progression. Conclusion: HAGLR could promote the progression of TNBC through the miR-93-5p/SRSF1 axis to activate the Wnt signaling pathway.