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S. Tseng

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    P1.05 - Poster Session 1 - Preclinical Models of Therapeutics/Imaging (ID 156)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.05-018 - Inhibition of Non-small-cell Lung Cancer Growth by pH Control Release Nanoparticle Carrying miR-135b Antagomir (ID 2707)

      09:30 - 16:30  |  Author(s): S. Tseng

      • Abstract

      We identified an intronic miRNA, miR-135b, up-regulated in aggressive non-small-cell lung cancer(NSCLC). Ectopically delivering mir-135b enhanced cell invasive and migratory ability in vitro and in vivo; whereas specific inhibition of miR-135b by miR-135b-specific molecular sponge and antagomirs suppressed cancer cell invasion, orthotopic lung tumor growth and metastasis in mouse model. We showed that miR-135b could directly repress the expression of Hippo pathway components. In this study, we design a tunable pH-responsive hydrogels to enhance the bioactivity of chemically modified antisense RNA oligonucleotide and SPION in tumor microenvironment for acidosis-related tumor therapy.

      pH-responsive matrix of PEG-imidazole hydrogel releases chemically modified oligonucleotides (antagomir) and positively charged superparamagnetic iron oxide nanoparticles (SPION) were prepared. NOD-SCID mice were subcutaneously injected with CL1-5 cells and control antagomiR or antagomir-135b was intra-tumoural injected for 3 weeks. Body weight was determined. Blood was collected before euthanasia. Total tumor volume, metastatic nodules, and miR-135b expression are measured.

      By using pH-responsive release of SPION from hydrogels to release antagomiR, we found the hydrogel administered to natural physiology had a rate of slower release at pH6.7 than at pH7.4, which is sufficient to restrain cellular uptake of antagomir and the rate of release in acidic environments can be manipulated via the imidazole content. .In addition, systematic administrated antagomiR-135b through I.V. injection inhibited the orthotopic lung tumor growth and decreased the volume of lung metastases. Both results trigger us to examine the possibility of in vivo placing the antagomiR-containing hydrogels by the side of tumor, to evaluate the effect of localized releasing antagomiR on tumor growth.

      Our results support that inhibition of miR-135b by pH control release nanoparticle may be promising to develop a new therapeutic strategy for NSCLC.