Search

CN-121987593-A - Targeted nanoparticle for treating acute respiratory distress syndrome as well as preparation method and application thereof

CN121987593ACN 121987593 ACN121987593 ACN 121987593ACN-121987593-A

Abstract

The invention relates to the technical field of bioengineering, in particular to a targeting nanoparticle for treating acute respiratory distress syndrome and a preparation method and application thereof. The preparation method comprises the steps of (1) combining MP peptide with DSPE-PEG 2000 -MAL through maleimide-thiol reaction, dialyzing, washing and freeze-drying the obtained conjugate to obtain the DSPE-PEG 2000 -MP conjugate, and (2) mixing the conjugate, lipid, a pharmaceutical preparation and a solvent, removing the solvent to obtain a lipid membrane, hydrating the lipid membrane, and extruding the membrane to obtain the nanoparticle. The invention not only provides a novel efficient and safe ARDS treatment scheme, but also provides an innovative mode for designing a nano drug delivery system based on cell mediation. The double targeting capability, excellent anti-inflammatory efficacy and good biocompatibility of the compound have wide prospect in clinical application.

Inventors

  • GAO CHUNSHENG
  • YANG MEIYAN
  • GONG WEI
  • TIAN HAO
  • YANG YANG
  • WANG YULI

Assignees

  • 中国人民解放军军事科学院军事医学研究院

Dates

Publication Date
20260508
Application Date
20260403

Claims (10)

  1. 1. A method of preparing targeted nanoparticles for the treatment of acute respiratory distress syndrome comprising the steps of: (1) Combining MP peptide with DSPE-PEG 2000 -MAL through maleimide-thiol reaction, dialyzing, washing and freeze-drying the obtained conjugate to obtain DSPE-PEG 2000 -MP conjugate; (2) Mixing the DSPE-PEG 2000 -MP conjugate, lipid, a pharmaceutical preparation and a solvent, removing the solvent to obtain a lipid membrane, hydrating the lipid membrane, and extruding the hydrated lipid membrane through the membrane to obtain the nanoparticle.
  2. 2. The preparation method of claim 1, wherein the amino acid sequence of the MP peptide in the step (1) is CYNFTNRKISVQRLASYRRITSSK, and the ratio of the MP peptide to DSPE-PEG 2000 -MAL is 100 mg:1.0-1.2 molar equivalents.
  3. 3. The preparation method according to claim 1, wherein the dialysis molecular weight cut-off value in the step (1) is 0.9-1.1 kDa, and the washing is washing with water for 20-28 h.
  4. 4. The preparation method of claim 1, wherein the lipid in the step (2) is DOPC, cationic liposome, DSPE-PEG 2000 and cholesterol in a mass ratio of 3-8:1-5:1-2:1-4; The cationic liposome is one of DDAB or DOTAP.
  5. 5. The method of claim 1, wherein the ratio of DSPE-PEG 2000 -MP conjugate, lipid, pharmaceutical formulation and solvent in step (2) is 1:80-90:10-15:10000.
  6. 6. The method of claim 1, wherein the pharmaceutical formulation of step (2) is methylprednisolone, dexamethasone or prednisone.
  7. 7. The method of claim 1, wherein the step (2) of passing the film extrusion is performed by passing polycarbonate films having pore diameters of 400, 200 and 80 nm in this order.
  8. 8. The targeted nanoparticle for treating acute respiratory distress syndrome prepared by the preparation method of any one of claims 1-7.
  9. 9. Use of the nanoparticle of claim 8 for the preparation of a nanoplatform for layered targeting of acute respiratory distress syndrome using monocyte delivery.
  10. 10. Use of the nanoparticle of claim 8 in the manufacture of a medicament for the treatment of acute respiratory distress syndrome.

Description

Targeted nanoparticle for treating acute respiratory distress syndrome as well as preparation method and application thereof Technical Field The invention relates to the technical field of bioengineering, in particular to a targeting nanoparticle for treating acute respiratory distress syndrome and a preparation method and application thereof. Background Acute lung injury and its severe form-Acute Respiratory Distress Syndrome (ARDS) are clinically significant problems. The disease is mainly characterized by rapid onset diffuse pulmonary inflammation, and the core driving factor is not direct invasion of pathogen, but excessive activation of the body immune system, leading to uncontrolled inflammatory reaction and high mortality. Pathologically, the pulmonary endothelial and epithelial barrier is destroyed, and vascular permeability is significantly increased, thereby causing pulmonary edema and gas exchange dysfunction. This process involves a sustained inflammatory cascade involving massive neutrophil infiltration and a cytokine storm dominated by macrophages. Although glucocorticoids can strongly inhibit inflammation, the systemic application of glucocorticoids has obvious limitations that the distribution of lung medicaments is extremely low, and serious complications such as secondary infection are easy to induce, thus limiting the clinical application of glucocorticoids. In order to break through the limitations of traditional drug delivery, it is critical to develop accurate drug delivery strategies. In recent years, cell-mediated nano-drug delivery systems have shown good application prospects. However, achieving efficient delivery in ARDS therapy presents a dual challenge in that, on the one hand, the drug needs to be efficiently enriched in the lungs in a short time to achieve the concentration required for treatment, and on the other hand, the "cell competition" caused by the large number of non-target cells in pathological conditions must be overcome to achieve accurate targeting at the cellular level. Our earlier studies explored anchoring drug nanoparticles to the surface of erythrocytes, utilizing pulmonary blood circulation properties to enhance drug accumulation. However, this strategy is difficult to regulate the immune microenvironment precisely due to the lack of active targeting ability to the inflammatory region. In addition, the complex in vitro preparation process and the requirement of autologous transfusion also seriously hamper clinical transformation. In the inflammatory process of ARDS, circulating monocytes are recruited to the lungs in large numbers and differentiate into a pro-inflammatory phenotype, a key factor driving the sustained deterioration of tissue damage. This makes infiltrating monocytes a very potential therapeutic target. Although monocyte-based drug delivery strategies have shown efficacy in a variety of diseases, due to the limited number of circulating monocytes in the body, it is difficult to rapidly achieve adequate drug enrichment in the infected lung, limiting its use in ARDS. Cationic lipid-based nanoparticles offer a promising solution to the above challenges. They not only have a natural tendency to enrich the lung, but also exhibit an intrinsic affinity for monocytes. However, how to effectively integrate this dual advantage into monocyte-mediated therapeutic strategies against ARDS remains a challenge. Achieving accurate targeting in the highly complex microenvironment of the inflammatory lung remains an exploratory stage, and significant non-targeted uptake often affects the final efficacy. Therefore, we propose an actively targeted collaborative nano platform-a cluster scout system. The design fuses the 'clustered' character of cationic lipid to realize the wide combination with circulating mononuclear cells, and simultaneously introduces the engineering peptide targeting specific receptor as a 'scout' component to strengthen the binding specificity of the mononuclear cells and actively guide the mononuclear cells to migrate to the inflammation site. It is assumed that the integration strategy can synchronously solve the double problems of organ level enrichment and cell level targeting, and provides a new idea for ARDS treatment. Disclosure of Invention The invention aims to provide a targeting nanoparticle for treating acute respiratory distress syndrome, and a preparation method and application thereof. The present invention employs a dual targeting strategy to combine passive lung affinity conferred by the cationic scaffold with a monocyte targeting peptide-directed active cell-mediated delivery pathway. The combination ensures the strong capture of the circulating monocytes to the nano particles, guides the active navigation of the circulating monocytes to the inflammatory lung, and realizes the efficient layered targeting. Experimental data of the present invention demonstrate that this "cluster-scout" synergistic mechanism achieves an unprec