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CN-121287946-B - Curcumin-loaded cerium-based nano-enzyme and preparation method and application thereof

CN121287946BCN 121287946 BCN121287946 BCN 121287946BCN-121287946-B

Abstract

The application belongs to the technical field of medicine preparation, and particularly relates to a curcumin-loaded cerium-based nano-enzyme, and a preparation method and application thereof. The curcumin-loaded cerium-based nano enzyme comprises a core carrier, a drug loaded on the core carrier and a shell, wherein the core carrier is a cerium-based metal organic framework, the drug is curcumin, and the shell is hyaluronic acid. The application provides an ultra-small nano enzyme HC@CeMOF with powerful antioxidation and targeting functions, and the data result of the application shows that the HC@CeMOF can be used for treating chronic pancreatitis. The method can be used for preferentially aggregating HC@CeMOF at a chronic pancreatic inflammation site by utilizing the inflammation targeting capability of hyaluronic acid, then effectively removing Reactive Oxygen Species (ROS) at a lesion site through the synergistic effect of curcumin and CeMOF, and down-regulating NF- κB expression, so that local inflammatory cytokine microenvironment is regulated, and finally pancreatic fibrosis is remarkably improved.

Inventors

  • LAI YONGKANG
  • YIN XIAOJING
  • WANG HUAN
  • SHU XU
  • OUYANG YONGLIANG
  • RONG JIANFANG

Assignees

  • 南昌大学第一附属医院

Dates

Publication Date
20260512
Application Date
20251210

Claims (7)

  1. 1. An application of curcumin-loaded cerium-based nano-enzyme in preparing a medicament for treating chronic pancreatitis is characterized in that, The curcumin-loaded cerium-based nano enzyme comprises a core carrier, a drug loaded on the core carrier and a shell; the core carrier is a cerium-based metal organic framework CeMOF, the drug is curcumin Cur, and the shell is hyaluronic acid.
  2. 2. The use according to claim 1, wherein the preparation method of the curcumin-loaded cerium-based nano-enzyme comprises the following steps: dispersing CeMOF nanometer enzyme powder in ethanol to obtain CeMOF suspension; dissolving curcumin in ethanol to obtain curcumin solution; Dissolving hyaluronic acid in water to obtain hyaluronic acid solution; mixing CeMOF suspension with curcumin solution for reaction, centrifuging after the reaction is finished, and freeze-drying to obtain Cur@CeMOF nano-enzyme; And dispersing the hyaluronic acid solution in the suspension of the cur@CeMOF nano enzyme, uniformly mixing, reacting, centrifuging, and freeze-drying to obtain the curcumin-loaded cerium-based nano enzyme.
  3. 3. The use according to claim 2, wherein the CeMOF nm enzyme powder is prepared by the steps of: Dissolving terephthalic acid in an organic solvent, adding (NH 4 ) 2 Ce(NO 3 ) 6 aqueous solution, stirring uniformly, transferring into a high-pressure reaction kettle, heating for reaction, cooling to room temperature after the reaction is finished, dialyzing, and freeze-drying to obtain CeMOF nanometer enzyme powder.
  4. 4. Use according to claim 3, characterized in that the (NH 4 ) 2 Ce(NO 3 ) 6 to terephthalic acid dosage ratio in the aqueous solution of (NH 4 ) 2 Ce(NO 3 ) 6 ) is 1.16 g:0.354 g.
  5. 5. The method according to claim 3, wherein the heating reaction is carried out at a temperature of 90 ℃ to 110 ℃ and a reaction time of 0.5 h to 1.5 h.
  6. 6. The use according to claim 2, wherein the CeMOF nm enzyme powder, curcumin, hyaluronic acid are used in a 5 mg:20 mg:1 mg ratio.
  7. 7. The use according to claim 6, wherein the CeMOF suspension has a concentration of 5 mg/mL; The concentration of the curcumin solution is 2 mg/mL, and the concentration of the hyaluronic acid solution is 1 mg/mL.

Description

Curcumin-loaded cerium-based nano-enzyme and preparation method and application thereof Technical Field The application belongs to the technical field of medicine preparation, and particularly relates to a curcumin-loaded cerium-based nano-enzyme, and a preparation method and application thereof. Background Chronic Pancreatitis (CP) is a lifelong, progressive fibrotic inflammatory disease caused by interactions of genetic and environmental factors. Clinically, CP can lead to exocrine pancreas and endocrine insufficiency, with recurrent pain, severely affecting the quality of life of the patient. In addition, it significantly increases the risk of pancreatic cancer. However, current treatments of CP rely mainly on palliative means such as enzyme substitution and nutritional support, and radical treatments have not been achieved. Therefore, developing safe and effective CP treatment strategies is of great importance for maintaining human health. Pancreatic fibrosis is a hallmark pathological feature of CP and is also a fundamental obstacle that is difficult to radically cure. Persistent and recurrent inflammatory stimuli are the primary driver of fibrosis, while Reactive Oxygen Species (ROS) act as key mediators in CP connecting inflammation with fibrosis. Under sustained inflammatory pressure, excessive ROS production and accumulation in the pancreas is caused by mechanisms such as mitochondrial dysfunction, abnormal activation of pancreatic enzymes, and respiratory burst of immune cells. These ROS directly induce oxidative damage to pancreatic cells and activate pro-inflammatory signaling pathways such as NF- κb, forming a vicious circle between inflammation and oxidative stress. At the same time, excess ROS promotes activation of Pancreatic Stellate Cells (PSCs) into fibromyofibroblasts, driving collagen deposition and pancreatic fibrosis, ultimately leading to irreversible tissue destruction. Thus, ROS are both "amplifiers" of inflammation and direct mediators of fibrosis, and targeting oxidative stress may provide a promising strategy for alleviating the pathological progression of CP. However, despite decades of research and several clinical trials, the efficacy of antioxidant therapy in CP remains controversial, and even research is questioning its clinical benefit. This inconsistency may result from anatomical features of the pancreas, which are located retroperitoneally, surrounded by vital organs and blood vessels, resulting in difficulty in penetration of the drug and direct access to the lesion. Furthermore, despite the abundance of pancreatic blood supply, maldistribution may limit the effective concentration of therapeutic drug throughout the organ. Thus, developing an efficient drug delivery strategy to enhance the bioavailability of antioxidants may be a viable solution to the challenges described above. Disclosure of Invention The invention aims to solve the defects of the prior art, and at least solves the problem of poor clinical curative effect caused by difficult pancreatic targeting, easy degradation and low bioavailability of an antioxidant in the prior art. According to the scheme, through nanocrystallization and targeted modification, the solubility and stability of the curcumin serving as a hydrophobic drug are obviously improved, the concentration of the curcumin at a focus part is improved, the treatment effect is enhanced, and meanwhile, systemic side effects are expected to be reduced, and the curcumin-loaded cerium-based nano-enzyme, the preparation method and the application thereof are specifically provided, and the following technical scheme is adopted: In a first aspect, the present invention provides a curcumin-loaded cerium-based nano-enzyme comprising a core carrier, a drug loaded on the core carrier, and a shell; The core carrier is a cerium-based metal organic framework, the drug is curcumin, and the shell is hyaluronic acid. The invention provides a curcumin-loaded cerium-based nano enzyme material with a 'core-shell structure', wherein a core is an ultra-small-size cerium-based metal organic framework (CeMOF) synthesized by a hydrothermal method, the CeMOF not only can be used as a drug carrier, but also has enzyme-like antioxidant activity (simulating SOD, CAT and the like), can effectively remove ROS, is a first functional core for treating chronic pancreatitis, and secondly, curcumin (Cur) is loaded in CeMOF, so that a strong anti-inflammatory and anti-fibrosis effect can be provided, and a PSCs activation and NF- κB and other pro-inflammatory signal paths can be inhibited, so that the curcumin-loaded cerium-based nano enzyme material is a second functional core of the invention. According to the invention, ceMOF is adopted as a core to remove excessive ROS, break through the malignant cycle of oxidative stress-inflammation and create a favorable microenvironment for Cur to play a role, and the Cur is adopted to inhibit inflammation and fibrosis processes, so that