Publications by authors named "Yiran Qu"

2 Publications

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Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization.

Pharmaceutics 2021 Apr 9;13(4). Epub 2021 Apr 9.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide SA5005, Australia.

Ferritin, one of the most investigated protein nanocages, is considered as a promising drug carrier because of its advantageous stability and safety. However, its short half-life and undesirable tumor targeting ability has limited its usage in tumor treatment. In this work, two types of functional peptides, half-life extension peptide PAS, and tumor targeting peptide RGDK (Arg-Gly-Asp-Lys), are inserted to human heavy-chain ferritin (HFn) at C-terminal through flexible linkers with two distinct enzyme cleavable sites. Structural characterizations show both HFn and engineered HFns can assemble into nanoparticles but with different apparent hydrodynamic volumes and molecular weights. RGDK peptide enhanced the internalization efficiency of HFn and showed a significant increase of growth inhibition against 4T1 cell line in vitro. Pharmacokinetic study in vivo demonstrates PAS peptides extended ferritin half-life about 4.9 times in Sprague Dawley rats. RGDK peptides greatly enhanced drug accumulation in the tumor site rather than in other organs in biodistribution analysis. Drug loaded PAS-RGDK functionalized HFns curbed tumor growth with significantly greater efficacies in comparison with drug loaded HFn.
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http://dx.doi.org/10.3390/pharmaceutics13040521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070472PMC
April 2021

Stability of Engineered Ferritin Nanovaccines Investigated by Combined Molecular Simulation and Experiments.

J Phys Chem B 2021 04 7;125(15):3830-3842. Epub 2021 Apr 7.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, South Australia 5005, Australia.

Human ferritin is regarded as an attractive and promising vaccine platform because of its uniform structure, good plasticity, and desirable thermal and chemical stabilities. Besides, it is biocompatible and presumed safe when used as a vaccine carrier. However, there is a lack of knowledge of how different antigen insertion sites on the ferritin nanocage impact the resulting protein stability and performance. To address this question, we selected Epstein-Barr nuclear antigen 1 as a model epitope and fused it at the DNA level with different insertion sites, namely, the N- and C-termini of ferritin, to engineer proteins E1F1 and F1E1, respectively. Protein properties including hydrophobicity and thermal, pH, and chemical stability were investigated both by molecular dynamics (MD) simulation and by experiments. Both methods demonstrate that the insertion site plays an important role in protein properties. The C-terminus insertion (F1E1) leads to a less hydrophobic surface and more tolerance to the external influence of high temperature, pH, and high concentration of chemical denaturants compared to N-terminus insertion (E1F1). Simulated protein hydrophobicity and thermal stability by MD were in high accordance with experimental results. Thus, MD simulation can be used as a valuable tool to engineer nanovaccine candidates, cutting down costs by reducing the experimental effort and accelerating vaccine design.
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http://dx.doi.org/10.1021/acs.jpcb.1c00276DOI Listing
April 2021