Polydopamine-Coated Kaempferol-Loaded MOF Nanoparticles: A Novel Therapeutic Strategy for Postoperative Neurocognitive Disorder

Abstract

Enhao Huang,1,2,* Huadao Li,2,3,* Hanghang Han,1,2,* Lianshan Guo,4 Yubing Liang,3 Zijin Huang,1 Ke Qin,5 Xueke Du1 1Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530007, People’s Republic of China; 2Key Laboratory for Basic Science and Prevention of Perioperative Organ Dysfunction, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 3Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 4Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530007, People’s Republic of China; 5Guilin People’s Hospital, Guilin, Guangxi Zhuang Autonomous Region, 541100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Qin; Xueke Du, Email [email protected]; [email protected]: The primary objective of this study was to develop an innovative nanomedicine-based therapeutic strategy to alleviate Postoperative Neurocognitive Disorder (PND) in patients undergoing surgery.Patients and Methods: To achieve this goal, polydopamine-coated Kaempferol-loaded Metal-Organic Framework nanoparticles (pDA/KAE@ZIF-8) were synthesized and evaluated. The study involved encapsulating Kaempferol (KAE) within ZIF-8 nanoparticles, followed by coating with polydopamine (PDA) to enhance biocompatibility and targeted delivery. The characterization of these nanoparticles (NPs) was conducted using various techniques including Scanning Electron Microscopy, Fourier-Transform Infrared Spectroscopy, X-ray Diffraction, and Ultraviolet-Visible spectroscopy. The efficacy of pDA/KAE@ZIF-8 NPs was tested in both in vitro and in vivo models, specifically focusing on their ability to penetrate the blood-brain barrier and protect neuronal cells against oxidative stress.Results: The study found that pDA/KAE@ZIF-8 NPs efficiently penetrated the blood-brain barrier and were significantly taken up by neuronal cells. These nanoparticles demonstrated remarkable Reactive Oxygen Species (ROS) scavenging capabilities and stability under physiological conditions. In vitro studies showed that pDA/KAE@ZIF-8 NPs provided protection to HT-22 neuronal cells against H2O2-induced oxidative stress, reduced the levels of pro-inflammatory cytokines, and decreased apoptosis rates. In a PND mouse model, the treatment with pDA/KAE@ZIF-8 NPs significantly improved cognitive functions, surpassing the effects of KAE alone. This improvement was substantiated through behavioral tests and a noted reduction in hippocampal inflammation.Conclusion: The findings from this study underscore the potential of pDA/KAE@ZIF-8 NPs as an effective nanotherapeutic agent for PND. This approach offers a novel direction in the postoperative care of elderly patients, with the potential to transform the therapeutic landscape for neurocognitive disorders following surgery. The application of nanotechnology in this context opens new avenues for more effective and targeted treatments, thereby improving the quality of life for patients suffering from PND.Keywords: nanomedicine, reactive oxygen species, blood-brain barrier

Keywords

• nanomedicine
• reactive oxygen species;blood-brain barrier.