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Dissertation_Congcong Xu_0515.pdf (23.44 MB)

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Optimizing the Physicochemical Properties of RNA Nanoparticles for Controllable Drug Release, Hydrophobic Drug Encapsulation and Enhanced Cancer Targeting

Xu, Congcong
http://rave.ohiolink.edu/etdc/view?acc_num=osu1589810873310799

Abstract Details

2020, Doctor of Philosophy, Ohio State University, Pharmaceutical Sciences.
The advancement of RNA nanotechnology in the past decade demonstrated its potentials as a new generation of drug for cancer treatment. However, nanoparticles encounter series of obstacles for successful drug delivery such as non-specific distribution, low release efficiency, heavy liver accumulation and other biological barriers. To address these issues for efficacious treatment, the RNA nano-delivery platform was engineered in terms of physical properties and chemistry characteristics to achieve favorable biodistribution, controlled drug release and enhanced cancer targeting. Chapter 1 gave an introduction of the RNA nanotechnology field and the current status of using RNA nanoparticles for biomedical applications. We discussed some key aspects of the pharmacokinetics of RNA nanomedicine including its distribution and elimination. Then we mentioned the challenges and limitations of RNA nanotechnology field which may hinder the clinical translation of this technology. In the following chapters, we further advanced RNA nanoplatform in order to address the abovementioned challenges. Chapter 2 described a controlled release scheme on RNA pyramid nanoparticles where the release of cargo could be cleaved from RNA nanocarrier with ease under the external light trigger. Chapter 3 showed the importance of controlling the surface chemistry of nanocage by encapsulation of hydrophobic molecules, which played a key role in reducing the non-specific interactions with cells and vital organs. Then we developed multivalent targeting strategy using MTX on RNA 3WJ nanoparticles as discussed in Chapter 4. Ligand valency has been manipulated to control the cancer targeting and biodistribution profile of RNA-MTX nanoparticles. In Chapter 5, we described a similar strategy in using multivalent small molecule DCL as ligands for specific PSMA targeting. The RNA nanoparticles were exploited for PET/CT imaging of prostate cancer with high specificity and sensitivity, providing image-guided therapy of prostate cancer. These studies focused on building up a relationship between the physicochemical properties of RNA nanoparticles with their pharmacokinetic profiles and pharmacological effects. In summary, with a more comprehensive understanding of how these characteristics regulate the performance of RNA nanoparticles, we will be able to improve the RNA nano-delivery system for optimized drug delivery and precision treatment.
Peixuan Guo (Advisor)
Sharyn Baker (Committee Member)
Robert Lee (Committee Member)
Rajgopal Govindarajan (Committee Member)
Tweedle Michael (Committee Member)
238 p.
Pharmaceuticals

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Citations

  • Xu, C. (2020). Optimizing the Physicochemical Properties of RNA Nanoparticles for Controllable Drug Release, Hydrophobic Drug Encapsulation and Enhanced Cancer Targeting [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1589810873310799

    APA Style (7th edition)

  • Xu, Congcong. Optimizing the Physicochemical Properties of RNA Nanoparticles for Controllable Drug Release, Hydrophobic Drug Encapsulation and Enhanced Cancer Targeting. 2020. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1589810873310799.

    MLA Style (8th edition)

  • Xu, Congcong. "Optimizing the Physicochemical Properties of RNA Nanoparticles for Controllable Drug Release, Hydrophobic Drug Encapsulation and Enhanced Cancer Targeting." Doctoral dissertation, Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1589810873310799

    Chicago Manual of Style (17th edition)

osu1589810873310799
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