Ultra-thermostable RNA nanoparticles for solubilizing and high-yield loading of paclitaxel for breast cancer therapy

Sijin Guo, Mario Vieweger, Kaiming Zhang, Hongran Yin, Hongzhi Wang, Xin Li, Shanshan Li, Shuiying Hu, Alex Sparreboom, B. Mark Evers, Yizhou Dong, Wah Chiu and Peixuan Guo ()
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Sijin Guo: The Ohio State University
Mario Vieweger: The Ohio State University
Kaiming Zhang: Stanford University
Hongran Yin: The Ohio State University
Hongzhi Wang: The Ohio State University
Xin Li: The Ohio State University
Shanshan Li: Stanford University
Shuiying Hu: The Ohio State University
Alex Sparreboom: The Ohio State University
B. Mark Evers: University of Kentucky
Yizhou Dong: The Ohio State University
Wah Chiu: Stanford University
Peixuan Guo: The Ohio State University

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract Paclitaxel is widely used in cancer treatments, but poor water-solubility and toxicity raise serious concerns. Here we report an RNA four-way junction nanoparticle with ultra-thermodynamic stability to solubilize and load paclitaxel for targeted cancer therapy. Each RNA nanoparticle covalently loads twenty-four paclitaxel molecules as a prodrug. The RNA-paclitaxel complex is structurally rigid and stable, demonstrated by the sub-nanometer resolution imaging of cryo-EM. Using RNA nanoparticles as carriers increases the water-solubility of paclitaxel by 32,000-fold. Intravenous injections of RNA-paclitaxel nanoparticles with specific cancer-targeting ligand dramatically inhibit breast cancer growth, with nearly undetectable toxicity and immune responses in mice. No fatalities are observed at a paclitaxel dose equal to the reported LD50. The use of ultra-thermostable RNA nanoparticles to deliver chemical prodrugs addresses issues with RNA unfolding and nanoparticle dissociation after high-density drug loading. This finding provides a stable nano-platform for chemo-drug delivery as well as an efficient method to solubilize hydrophobic drugs.

Date: 2020
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DOI: 10.1038/s41467-020-14780-5

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