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RNA Nanoparticles for Anti-Oncogenic miRNA and Drug Delivery for Cancer Therapy- [electronic resource]
RNA Nanoparticles for Anti-Oncogenic miRNA and Drug Delivery for Cancer Therapy- [electronic resource]
상세정보
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214101940
- ISBN
- 9798380200929
- DDC
- 616.99
- 저자명
- Yin, Hongran.
- 서명/저자
- RNA Nanoparticles for Anti-Oncogenic miRNA and Drug Delivery for Cancer Therapy - [electronic resource]
- 발행사항
- [S.l.]: : The Ohio State University., 2020
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2020
- 형태사항
- 1 online resource(163 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-03, Section: B.
- 주기사항
- Advisor: Guo, Peixuan.
- 학위논문주기
- Thesis (Ph.D.)--The Ohio State University, 2020.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 요약RNA can serve as powerful building blocks for biotechnological and biomedical applications. A variety of RNA architectures can be constructed via bottom-up self-assembly such as RNA polygons, RNA polyhedrons, RNA dendrimers, etc. The three-way junction (3WJ) motif, derived from packaging RNA (pRNA) of bacteriophage phi29 DNA packaging motor, emerges as a novel and robust delivery platform. The high thermodynamic and chemical stability enables the delivery of therapeutics incorporated to the 3WJ scaffold.In the first study, RNA nanoparticles are functioned with a RNA aptamer binding to CD133 receptor, which is overexpressed in triple negative breast cancer (TNBC), to deliver an 8 nt locked nuclei acid (LNA) sequence for miRNA21 inhibition (anti-miR21). In vitro and in vivo studies revealed that these therapeutic RNA nanoparticles can bind to CD133 positive TNBC cells specifically, upregulate downstream tumor suppressors' expression efficiently, and reduce the invasive properties of tumor cells effectively. No obvious toxicity or immunogenicity has been detected. Systemic injection of these RNA nanoparticles in animal trial demonstrated high specificity for TNBC tumor targeting and high efficacy for tumor growth inhibition. Besides, 3WJ RNA scaffold is able to accommodate chemical drug Camptothecin (CPT) to improve its water solubility, further specifically target tumor by the incorporation of folic acid (or folate, FA) ligand.In addition to current self-assembly strategies utilizing base paring and RNA tertiary interactions, RNA based micellar nanoparticles are constructed by conjugating a cholesterol molecule onto one helical end of the 3WJ motif. RNA micelles can be assembled by the hydrophobic force, composed of a lipid core and a 3WJ-RNA corona. Our study indicated RNA micelles can deliver therapeutics to tumor and inhibit its growth, while the inclusion of FA as an active targeting ligand in the micelles did not improve the therapeutic efficacy significantly in vivo. The proposed mechanism for micelles' tumor targeting capability without the need of ligand is due to the size of micelles (~20nm) within the lower end of the nanometer scale that favoring Enhanced Permeability and Retention (EPR) effect. Take advantage of high stability and multivalence, RNA micelles are capable of delivering miRNA, anti-miRNA, siRNA as well as chemical drugs for cancer therapy, especially when targeting ligands are not available.In the third study, the rational design of incorporating siRNA to 3WJ scaffold is exploited. Several factors that may affect Dicer processing of siRNA were investigated, including base pairing length, 3'-overhang and chemical modification. The data provides some hints on the strategy of attaching siRNA to 3WJ motif for efficient processing by Dicer enzyme. To illustrate the processing, 3WJ-siRNA based molecular beacon was built utilizing a pair of fluorophore/quencher. This molecular beacon delivered by FA decorated exosomes, which are developed in our lab as a cytosol delivery vesicle, is able to sense the dynamic siRNA processing intracellularly by monitoring fluorescence signal.In sum, these studies demonstrate the versatile application of RNA nanotechnology and provide the basis for future clinical translation.
- 일반주제명
- Pharmaceutical sciences.
- 일반주제명
- Oncology.
- 일반주제명
- Genetics.
- 키워드
- RNA polyhedrons
- 키워드
- RNA polygons
- 키워드
- Packaging RNA
- 키워드
- Cancer therapy
- 기타저자
- The Ohio State University Pharmacy
- 기본자료저록
- Dissertations Abstracts International. 85-03B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008240612s2020 us |||||||||||||||c||eng d■001000016935504
■00520240214101940
■006m o d
■007cr#unu||||||||
■020 ▼a9798380200929
■035 ▼a(MiAaPQ)AAI30725525
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.99
■1001 ▼aYin, Hongran.
■24510▼aRNA Nanoparticles for Anti-Oncogenic miRNA and Drug Delivery for Cancer Therapy▼h[electronic resource]
■260 ▼a[S.l.]:▼bThe Ohio State University. ▼c2020
■260 1▼aAnn Arbor :▼bProQuest Dissertations & Theses, ▼c2020
■300 ▼a1 online resource(163 p.)
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-03, Section: B.
■500 ▼aAdvisor: Guo, Peixuan.
■5021 ▼aThesis (Ph.D.)--The Ohio State University, 2020.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aRNA can serve as powerful building blocks for biotechnological and biomedical applications. A variety of RNA architectures can be constructed via bottom-up self-assembly such as RNA polygons, RNA polyhedrons, RNA dendrimers, etc. The three-way junction (3WJ) motif, derived from packaging RNA (pRNA) of bacteriophage phi29 DNA packaging motor, emerges as a novel and robust delivery platform. The high thermodynamic and chemical stability enables the delivery of therapeutics incorporated to the 3WJ scaffold.In the first study, RNA nanoparticles are functioned with a RNA aptamer binding to CD133 receptor, which is overexpressed in triple negative breast cancer (TNBC), to deliver an 8 nt locked nuclei acid (LNA) sequence for miRNA21 inhibition (anti-miR21). In vitro and in vivo studies revealed that these therapeutic RNA nanoparticles can bind to CD133 positive TNBC cells specifically, upregulate downstream tumor suppressors' expression efficiently, and reduce the invasive properties of tumor cells effectively. No obvious toxicity or immunogenicity has been detected. Systemic injection of these RNA nanoparticles in animal trial demonstrated high specificity for TNBC tumor targeting and high efficacy for tumor growth inhibition. Besides, 3WJ RNA scaffold is able to accommodate chemical drug Camptothecin (CPT) to improve its water solubility, further specifically target tumor by the incorporation of folic acid (or folate, FA) ligand.In addition to current self-assembly strategies utilizing base paring and RNA tertiary interactions, RNA based micellar nanoparticles are constructed by conjugating a cholesterol molecule onto one helical end of the 3WJ motif. RNA micelles can be assembled by the hydrophobic force, composed of a lipid core and a 3WJ-RNA corona. Our study indicated RNA micelles can deliver therapeutics to tumor and inhibit its growth, while the inclusion of FA as an active targeting ligand in the micelles did not improve the therapeutic efficacy significantly in vivo. The proposed mechanism for micelles' tumor targeting capability without the need of ligand is due to the size of micelles (~20nm) within the lower end of the nanometer scale that favoring Enhanced Permeability and Retention (EPR) effect. Take advantage of high stability and multivalence, RNA micelles are capable of delivering miRNA, anti-miRNA, siRNA as well as chemical drugs for cancer therapy, especially when targeting ligands are not available.In the third study, the rational design of incorporating siRNA to 3WJ scaffold is exploited. Several factors that may affect Dicer processing of siRNA were investigated, including base pairing length, 3'-overhang and chemical modification. The data provides some hints on the strategy of attaching siRNA to 3WJ motif for efficient processing by Dicer enzyme. To illustrate the processing, 3WJ-siRNA based molecular beacon was built utilizing a pair of fluorophore/quencher. This molecular beacon delivered by FA decorated exosomes, which are developed in our lab as a cytosol delivery vesicle, is able to sense the dynamic siRNA processing intracellularly by monitoring fluorescence signal.In sum, these studies demonstrate the versatile application of RNA nanotechnology and provide the basis for future clinical translation.
■590 ▼aSchool code: 0168.
■650 4▼aPharmaceutical sciences.
■650 4▼aOncology.
■650 4▼aGenetics.
■653 ▼aClinical translation
■653 ▼aBiomedical applications
■653 ▼aRNA polyhedrons
■653 ▼aRNA polygons
■653 ▼aPackaging RNA
■653 ▼aCancer therapy
■690 ▼a0572
■690 ▼a0992
■690 ▼a0369
■71020▼aThe Ohio State University▼bPharmacy.
■7730 ▼tDissertations Abstracts International▼g85-03B.
■773 ▼tDissertation Abstract International
■790 ▼a0168
■791 ▼aPh.D.
■792 ▼a2020
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16935504▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202402▼f2024
