2. Academic Validation
  3. Living Macrophage-Delivered Tetrapod PdH Nanoenzyme for Targeted Atherosclerosis Management by ROS Scavenging, Hydrogen Anti-inflammation, and Autophagy Activation

Living Macrophage-Delivered Tetrapod PdH Nanoenzyme for Targeted Atherosclerosis Management by ROS Scavenging, Hydrogen Anti-inflammation, and Autophagy Activation

  • ACS Nano. 2022 Oct 11. doi: 10.1021/acsnano.2c03422.
Ruizhi Hu 1,  Chen Dai 1,  Caihong Dong 2,  Li Ding 3,  Hui Huang 4,  Yu Chen 4,  Bo Zhang 1
Affiliations

Affiliations

  • 1 Department of Medical Ultrasound, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P. R. China.
  • 2 Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
  • 3 Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai 200072, P. R. China.
  • 4 Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, P. R. China.
PMID: 36219731 DOI: 10.1021/acsnano.2c03422
Abstract

Atherosclerosis, driven by chronic inflammation in the artery walls, underlies several severe cardiovascular diseases. However, currently available anti-inflammatory-based strategies for atherosclerosis treatment suffer from compromised therapeutic efficacy and undesirable therapeutic outcome. Herein, a distinct tetrapod needle-like PdH nanozyme was designed and engineered for efficient atherosclerosis treatment by the combinatorial Reactive Oxygen Species (ROS) scavenging, hydrogen anti-inflammation, and Autophagy activation. After loading into macrophages and targeted delivery to arterial plaques, these multifunctional nanozymes efficiently decreased the ROS levels and significantly suppressed the inflammation-related pathological process, exerting the distinct antioxidation and anti-inflammatory performance for alleviating atherosclerosis development. Especially and importantly, the specific spiky morphology of the PdH nanoenzyme further triggered a strong Autophagy response in macrophages, synergistically maintaining the cellular homeostasis and alleviating atherosclerosis development. Both in vitro and in vivo results confirmed the synergy among the antioxidation, anti-inflammatory, and Autophagy activation, suggesting that the combinatorial engineering of nanomedicines with intrinsic multiple therapeutic functions and topology-induced biological effects is highly preferable and effective for achieving the high therapeutic performance and desirable therapeutic outcome on atherosclerosis management and therapy.

Keywords

PdH; ROS scavenge; atherosclerosis; autophagy; gas therapy; nanozyme; tetrapod.

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