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CN-122005844-A - Magnetocaloric nanoparticle for targeted activation of cell membrane TRPV1 as well as preparation method and application thereof

CN122005844ACN 122005844 ACN122005844 ACN 122005844ACN-122005844-A

Abstract

The invention relates to the technical field of biological medicines, and particularly provides a magnetocaloric nanoparticle for targeted activation of cell membrane TRPV1, and a preparation method and application thereof. After FeNPs surface modification of PEG long-circulating lipid DSPE-PEG2000 molecules, a special cell membrane external TRPV1 monoclonal antibody is added, and FeNPs-TRPV1 particles are obtained by utilizing an aminocarboxylic acid reaction. The FeNPs-TRPV1 particle provided by the invention has a magneto-thermal conversion effect, the FeNPs is precisely sent to the periphery of the TRPV1 on the surface of a cell membrane by a cell membrane external TRPV1 monoclonal antibody, and an external TRPV1 channel of the cell membrane is activated by heating by an alternating magnetic field, so that calcium ion inflow is caused, the nociceptive nerve signal of myocardial ischemia reperfusion injury is regulated and controlled, and the myocardial ischemia reperfusion injury is effectively alleviated.

Inventors

  • HE SHUFANG
  • CHENG XUEYING
  • ZHANG YE
  • YANG FANG
  • LIU SHUANGYU
  • ZHANG YU
  • Qi Le Mu Ge
  • WU CHAO

Assignees

  • 安徽医科大学第二附属医院

Dates

Publication Date
20260512
Application Date
20241111

Claims (10)

  1. 1. A preparation method of magnetocaloric nano-particles FeNPs-TRPV1 is characterized by comprising the steps of modifying PEGylated long-circulating lipid DSPE-PEG2000 molecules on the surface of FeNPs, adding a cell membrane external TRPV1 monoclonal antibody, and obtaining the magnetocaloric nano-particles FeNPs-TRPV1 by utilizing an aminocarboxylic acid reaction.
  2. 2. The preparation method of the trichloromethane, according to claim 1, wherein FeNPs is obtained by mixing, heating, nucleating and curing iron acetylacetonate, oleic acid and oleylamine, naturally cooling and washing FeNPs, and preserving in chloroform at constant volume.
  3. 3. The method of any one of claims 1-2, wherein the FeNPs and lipid DSPE-PEG2000 molecules are sonicated at 70 ℃ for 10-15 min to obtain FeNPs coated with DSPE-PEG2000-COOH phospholipid molecules.
  4. 4. The method according to claim 3, wherein EDC and NHS are added to a solution of FeNPs coated with DSPE-PEG2000-COOH phospholipid molecules, and then the cell membrane-external TRPV1 antibody is added to the solution, followed by stirring and filtering off the excess TRPV1 antibody to obtain FeNPs-TRPV1.
  5. 5. The method according to claim 4, wherein the mass ratio of the extracellular antibody to FeNPs of the surface-coated DSPE-PEG2000-COOH phospholipid molecule is 1:50, and the stirring is performed at 4 ℃ for 24 hours.
  6. 6. A magnetocaloric nanoparticle FeNPs-TRPV1, characterized in that it is obtainable by the preparation process according to any one of claims 1 to 5.
  7. 7. An agent comprising the magnetocaloric nanoparticle FeNPs-TRPV1 of claim 6.
  8. 8. Use of the magnetocaloric nanoparticle FeNPs-TRPV1 of claim 6 or the agent of claim 7 for alleviating myocardial ischemia reperfusion injury.
  9. 9. A method of alleviating myocardial ischemia reperfusion injury, comprising activating a TRPV1 channel with the magnetocaloric nanoparticle FeNPs-TRPV1 of claim 6 prior to myocardial ischemia reperfusion.
  10. 10. The method of claim 9, wherein the magnetocaloric nanoparticle FeNPs-TRPV1 is injected into spinal cord tissue, and myocardial ischemia reperfusion is performed after activation of spinal cord TRPV1 channels.

Description

Magnetocaloric nanoparticle for targeted activation of cell membrane TRPV1 as well as preparation method and application thereof Technical Field The invention relates to the technical field of biological medicines, and particularly provides a magnetocaloric nanoparticle for targeted activation of cell membrane TRPV1, and a preparation method and application thereof. Background Ischemic heart disease (ISCHEMIC HEART DISEASE, IHD) is one of the diseases with highest disability rate and mortality rate in China or even worldwide. After myocardial ischemia, timely reperfusion is the most effective current therapeutic strategy, capable of significantly reducing mortality associated with IHD. However, the occurrence of myocardial Ischemia Reperfusion Injury (IRI) significantly reduces the positive effects of reperfusion therapy. Furthermore, myocardial IRI exacerbates ischemic injury, increases the risk of arrhythmia and myocardial infarction volume, and even leads to patient death, thereby affecting patient prognosis, and currently there is still a lack of effective clinical intervention for myocardial IRI. Basic studies have shown that cardiac sensory neurons can experience stimulation of H + and lactate, adenosine (ATP), bradykinin (BK), etc. during ischemia reperfusion and transmit nociceptive signals to the thoracic spinal cord and superior central nerve via the Dorsal Root Ganglion (DRG), resulting in chest pain and sympathetic excitation, which in turn places a cardiac burden and injury. Therefore, aiming at the potential mechanism of the myocardial IRI, the accurate regulation and control of cardiac nociceptive signaling are realized, and the method has important significance for relieving the myocardial IRI injury. TRPV1 is a thermosensitive ion channel located on the cell membrane and is known to open when temperatures exceed 42 ℃. This opening of the channel promotes the influx of positively charged ions (particularly calcium ions) thereby activating the downstream signal pathway. Endogenous mediators produced during the ischemia and reperfusion phases may stimulate transient receptor potential vanillic acid 1 (TRPV 1) positive cardiac afferent neurons. Early studies found that inhibiting TRPV1 activation in the Dorsal Root Ganglion (DRG) or spinal cord could be effective in reducing nociceptive signaling and reducing cardiac injury during ischemia reperfusion. From this, it is clear that the role of TRPV1 activation in myocardial Ischemia Reperfusion Injury (IRI) is not clear, and that TRPV1 effects are both detrimental and cardioprotective. Therefore, the development of a target activating cell membrane TRPV1 to alleviate myocardial IRI has great clinical significance. Disclosure of Invention The invention aims to alleviate or mitigate myocardial ischemia reperfusion injury. The inventors found that activation of TRPV1 by capsaicin pretreatment can trigger cardioprotection by releasing Calcitonin Gene Related Peptide (CGRP) and Substance P (SP) in animals receiving Remote Ischemia Pretreatment (RIPC). Thus, it is speculated that moderate TRPV1 activation may have the advantage of protecting against myocardial damage, whereas excessive activation during ischemic events may lead to adverse consequences. Based on the characteristics that the spinal cord dorsal horn expresses TRPV1 and participates in a myocardial IRI mechanism, the invention provides a magnetocaloric nanoparticle FeNPs-TRPV1 for targeted activation of cell membrane TRPV1, a preparation method and application, wherein magnetic nanoparticles FeNPs are connected with TRPV1 antibodies, feNPs-TRPV1 is targeted and transferred to the periphery of the cell membrane surface TRPV1 by utilizing the characteristic of targeting action of primary antibodies and receptors, and then a spinal cord TRPV1 channel is moderately activated by the heating action of an external alternating magnetic field on FeNPs, so that the aim of relieving myocardial IRI is fulfilled. In a first aspect, the invention provides a preparation method of magnetocaloric nano-particles FeNPs-TRPV1, which comprises the steps of adding a cell membrane external TRPV1 monoclonal antibody after modifying a PEGylated long-circulating lipid DSPE-PEG2000 molecule on the surface of FeNPs, and obtaining the magnetocaloric nano-particles FeNPs-TRPV1 by utilizing an aminocarboxylic acid reaction. In the preparation method provided by the invention, feNPs is obtained by mixing, heating, nucleating and curing ferric acetylacetonate, oleic acid and oleylamine, naturally cooling and washing FeNPs, and preserving in chloroform at constant volume. In the preparation method provided by the invention, feNPs and lipid DSPE-PEG2000 molecules are subjected to ultrasonic treatment at 70 ℃ for 10-15 min, so as to obtain FeNPs of which the surface is coated with DSPE-PEG2000-COOH phospholipid molecules. In the preparation method provided by the invention, EDC and NHS are added into a FeNPs solution of whic