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  • 09월 08일 17시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제116회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Enhanced cancer therapy by delivering self-assembled RNAi nanoparticles against multiple targets and chemotherapeutic agent to overcome chemoresistance

2015년 9월 8일 11시 57분 57초
BIO.P-222 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
10월 15일 (목요일) 11:00~12:30
저자 및
장미희, 안형준1,*
한국과학기술연구원(KIST) 테라그노시스연구단, Korea
1한국과학기술연구원(KIST) 테라그노시스, Korea
Chemoresistance is a major obstacle in an effective treatment of chemotherapy. We have developed an enhanced cancer therapy to overcome multi-drug resistance (MDR) by using combinatory strategy that delivers multiple siRNA which can co-silence the expression of efflux transporter and anti-apoptotic protein, as well as treats anticancer drug. Here, we report that folate -decorated RNAi nanoparticles (Dsi RNPs) via self-assembly system, synthesized by rolling circle transcriptions (RCT) and sequence-specific hybridization with folate-DNA-Cholesterol (FA-DNA-CHOL) without aids of polycationic reagents, resulting in efficiently delivering multiple siRNA, which directed against P-glycoprotein (P-gp) and B-cell lymphoma 2 (BCL-2) mRNA, into MDR cancer cells (KB-V1 cells). Dsi RNPs exhibited effective multi- gene silencing efficiency within single nanoparticles with 93% of high siRNA loading capacity, given by multi-tandem of RNA hairpins generated by RCT into condensed RNA nanoparticles. Furthermore, Dsi RNPs allow to enable size-controllable construction and active-targeting uptake to drug-resistance cancer cells. In addition, our combination therapy demonstrated to increase the intracellular DOX concentration and induce remarkably enhanced cellular apoptosis particularly when administrated with Dsi RNPs and doxorubicine (DOX) sequentially in specific order of exposure than administrated simultaneously. Our Dsi RNPs platform showed to restore drug sensitivity in KB-V1 cells by overcoming pump and nonpump resistance. Taken together, our current study demonstrates the potential of combination therapy as an emergence of siRNA delivery and chemotherapy, resulting in synergistic cell killing effect and restorement of drug sensitivity to KB-V1 and enhanced efficacy of chemotherapy. Therefore, our study suggest a promising strategy to improve therapeutic potentials in MDR cancer therapy.