Development of Multifunctional Cancer Therapeutic Nano-complex for RNAi Therapy
- 발행기관 서강대학교 일반대학원
- 지도교수 오병근
- 발행년도 2014
- 학위수여년월 2014. 2
- 학위명 박사
- 학과 및 전공 도움말 일반대학원 화공생명공학과
- 실제URI http://www.dcollection.net/handler/sogang/000000052755
- 본문언어 영어
- 저작권 서강대학교 논문은 저작권 보호를 받습니다.
초록/요약 도움말
Multifunctional nanomaterials have been developed drastically as nano-carrier for molecular imaging and cancer treatment because of ease for synthesis, multi-functionality and low cytotoxicity. Multifunctional nanomaterials have several advantages in functionality originated in property of including several biomaterials such as targeting ligand and chemotherapeutic agent. In this study, we developed 3 kinds of multifunctional nano-complex for cancer imaging and treatment, which are FITC doped silica nanoparticles, two-component nanorods and bovine serum albumin (BSA) – nanorods complex. First, FITC-doped silica nanoparticles (SiNPs) were exploited for imaging of cancer cell and delivery of siRNA in order to induce cancer cell apoptosis. SiNPs have developed surface modification using HIV-1 trans-activating transcriptional activator (HIV1-TAT) peptides. The HIV1-TAT peptides (cell-penetrating peptides) are able to deliver cargos such as oligonucleotides and proteins across the plasma membrane and into living cancer cells. The knockdown effect of specific protein by siRNA on silica nanoparticles was evaluated by using green fluorescent protein stable cell line. Second, two-component nanorods with gold (Au) block and nickel (Ni) block have developed for targeting delivery of siRNA, dual-fluorescence imaging of cancer cell and treatment. FITC labeled LHRH (Luteinizing hormone-releasing hormone) peptides are attached on surface of Ni block for targeting delivery of breast cancer cell, MCF-7, through interaction of histidine tagged LHRH and the surface of Ni block. The Au block was modified with TAMRA labeled thiolated siRNA in order to knock down VEGF (vascular endothelial growth factor) protein and induce the death of breast cancer cell. These multi-component nanorods can be internalized by active targeting and induced extinction the MCF-7 cell through RNA interference mechanism. Finally, thermo-responsive siBcl-2 and rod encapsulated BSA nano-complex (SREB) was developed to enhance the biocompatibility and therapeutic effect. The SREB complex is functionalized by poly-ethyleneglycol (PEG) and anti-HER2 for targeting delivery. Au nanorods (AuNRs) were loaded into biocompatible albumin based nano-complexes. The photothermal induced death and RNAi effect using encapsulated siBcl-2 exhibits synergetic effect on photothermal cancer treatment. These three kinds of nano-complex was acheived successful cancer treatment with siRNA therapy.
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