Abstract
Nanoparticle-Based therapeutics represent potential strategies for treating atherosclerosis; however, the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells. Here, we report reactive oxygen species (ROS)-responsive and size-reducible nano assemblies, formed by multivalent host-guest interactions between β-cyclodextrins (β-CD)-anchored discoidal recombinant high-density lipoprotein (NP3ST) and hyaluronic acid-ferrocene (HA-Fc) conjugates. the HA-Fc/NP3ST nano assemblies have extended blood circulation time, specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium, rapidly disassemble in response to excess ROS in the intimal and release smaller NP3ST, allowing for further plaque penetration, macrophage-targeted cholesterol efflux and drug delivery. in vivo pharmacodynamics in atherosclerotic mice shows that HA-Fc/NP3ST reduces plaque size by 53%, plaque lipid deposition by 63%, plaque macrophage content by 62% and local inflammatory factor level by 64% compared to the saline group. Meanwhile, HA-Fc/NP3ST alleviates systemic inflammation characterized by reduced serum inflammatory factor levels. Collectively, HA-Fc/NP3ST nano assemblies with ROS-responsive and size-reducible properties exhibit a deeper penetration in atherosclerotic plaque and enhanced macrophage targeting ability, thus exerting effective cholesterol efflux and drug delivery for atherosclerosis therapy.
Recommended Citation
J. He and W. Zhang and X. Zhou and F. Xu and J. Zou and Q. Zhang and Y. Zhao and H. He and H. Yang and J. Liu, "Reactive Oxygen Species (Ros)-Responsive Size-Reducible Nanoassemblies for Deeper Atherosclerotic Plaque Penetration and Enhanced Macrophage-Targeted Drug Delivery," Bioactive Materials, vol. 19, pp. 115 - 126, Elsevier; KeAi Communications, Jan 2023.
The definitive version is available at https://doi.org/10.1016/j.bioactmat.2022.03.041
Department(s)
Chemical and Biochemical Engineering
Publication Status
Open Access
Keywords and Phrases
Atherosclerosis; Macrophage; Reactive oxygen species; Recombinant high-density lipoprotein; Size-reducible nanoassemblies
International Standard Serial Number (ISSN)
2452-199X
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2025 Elsevier; KeAi Communications, All rights reserved.
Publication Date
01 Jan 2023
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Biomedical Engineering and Bioengineering Commons, Chemical Engineering Commons
Comments
National Natural Science Foundation of China, Grant 81773669