CN-122005791-A - Lactic acid metabolism regulating nanometer preparation, preparation method and application

Abstract

The invention relates to the field of biological medicine, in particular to a lactic acid metabolism regulating nano preparation, a preparation method and application, wherein the lactic acid metabolism regulating nano preparation contains an oxygen-enriched phase-change agent as a core, the outside of the oxygen-enriched phase-change agent is wrapped with a liposome, the liposome is a cRGD peptide modified liposome, a GLUT-1 inhibitor is loaded on the liposome, the GLUT-1 inhibitor is BAY-876, and the oxygen-enriched phase-change agent is perfluorohexane. By the nano preparation, lactic acid can be regulated after HIFU operation, the generation of lactic acid is reduced, and the problems that cells in a sublethal heat stress area undergo metabolic disorder and lactic acid is generated in a large amount after HIFU operation are solved.

Inventors

• LI PAN
• HUANG ZEYAN
• HUANG JU
• ZHANG LIANG
• LIN YI
• TANG RUI

Assignees

• 重庆医科大学附属第一医院

Dates

Publication Date

20260512

Application Date

20260228

Claims (10)

1. 1. A nano-preparation for regulating lactic acid metabolism is characterized by containing an oxygen-enriched phase-change agent.
2. 2. The lactic acid metabolism-control nano-preparation according to claim 1, wherein the oxygen-enriched phase-change agent is used as a core, and the outside of the oxygen-enriched phase-change agent is coated with liposome.
3. 3. The lactic acid metabolism-regulating nano-preparation according to claim 2, wherein the liposome is cRGD peptide or a transmembrane peptide modified liposome.
4. 4. The lactic acid metabolism-control nano-preparation according to claim 2, wherein the GLUT-1 inhibitor is loaded on the liposome.
5. 5. The lactic acid metabolism-control nano-preparation according to claim 1, wherein the oxygen-enriched phase-change agent is perfluorohexane or PFP.
6. 6. Application of oxygen-enriched phase change agent in preparing medicine for reducing lactic acid generation by relieving sublethal heat stress under HIFU focusing is provided.
7. 7. The method of claim 6, wherein the oxygen-enriched phase change agent is perfluorohexane.
8. 8. Use of the lactate metabolism-modulating nanoformulation of claims 1-5 for the preparation of a medicament for reducing lactate production by reducing sublethal heat stress under HIFU focusing.
9. 9. The preparation method of the lactic acid metabolism regulating nano preparation is characterized by comprising the following steps: s1, dissolving DPPC, cRGD-DSPE-PEG 2000 and cholesterol in chloroform, adding BAY-876 and uniformly mixing; S2, removing the organic solvent by using a rotary evaporator, adding PBS for hydration, and stripping the phospholipid membrane under the assistance of an ultrasonic cleaner; s3, adding perfluorohexane, and carrying out sound vibration by a sound vibration instrument to obtain cRGD-lip@PFH-BAY liposome; S4, carrying out oxygenation treatment on the obtained liposome in an oxygen-enriched environment to obtain the oxygen-enriched cRGD-lip@PFH-BAY.
10. 10. The method for preparing a nano-preparation for regulating lactic acid metabolism as claimed in claim 9, wherein the nano-preparation comprises DPPC, cRGD-DSPE-PEG 2000 Dissolving in chloroform at a mass ratio of 3:1:1 with cholesterol.

Description

Lactic acid metabolism regulating nanometer preparation, preparation method and application Technical Field The invention relates to the field of biological medicine, in particular to a lactic acid metabolism regulating nano preparation, a preparation method and application. Background Hepatocellular carcinoma (HCC) is one of the highest global incidences of solid malignant tumors and is also the third leading cause of cancer-related death, patients often enter middle and late stages at diagnosis due to lack of early specific symptoms, and surgical resection adaptability and success rate are severely limited, so non-surgical topical treatment is the main clinical choice. High-intensity focused ultrasound (HIFU) has been demonstrated to safely and effectively achieve localized ablation of liver cancer by virtue of non-invasive, accurate positioning, real-time monitoring, and the like. However, as the depth of tissue penetration and blood flow perfusion increases, the ultrasonic energy decays exponentially in the tissue, resulting in insufficient energy deposition at the target area, insufficient thermal damage to a portion of the tissue, and formation of a sub-lethal heat stress zone. Although the cells in this region do not undergo coagulation necrosis, they undergo metabolic disorders, and are mainly represented by the large-scale production of Lactic Acid (LA). Accumulation of high concentration lactic acid in Tumor Microenvironments (TMEs) can impair proliferation and cytotoxicity of effector T cells and form immunosuppressive microenvironments by promoting macrophage polarization to the pro-tumor M2 phenotype, thereby promoting malignant proliferation and increasing recurrence risk. In the prior art, the intervention on the lactic acid metabolism of tumors has obvious shortboards, firstly, early researches focus on 'passively clearing generated lactic acid', but the strategies can not block the tumor cells to continuously synthesize lactic acid through Warburg effect, and the tumor can not be inhibited from continuously growing, secondly, partial researches try to actively intervene in the lactic acid generation source, such as X, meng et al, adopt hexokinase 2 (HK 2) inhibitor to block the first step of glycolysis, but only inhibit HK2 can cause intracellular glucose accumulation, trigger other metabolic compensation ways, and can not realize thorough energy shortage of tumor cells, thirdly, the research is carried out on oxidizing glucose by glucose oxidase (Gox) to reduce the intracellular glucose level, but the activity of Gox is highly dependent on environmental factors such as pH, temperature and the like, and the anoxic microenvironment inside the tumor can obviously weaken the efficacy, so that the clinical transformation is limited. Therefore, how to regulate lactic acid after HIFU operation and reduce lactic acid production is still a urgent problem to be solved. Disclosure of Invention The invention aims to provide a lactic acid metabolism regulating nano preparation, a preparation method and application thereof, so that lactic acid is regulated after HIFU operation, the generation of lactic acid is reduced, and the problems that cells in a sublethal heat stress area undergo metabolic disorder and lactic acid is generated in a large amount after HIFU operation are solved. In order to achieve the purpose, the invention adopts the following technical scheme that the lactic acid metabolism regulating nano preparation contains an oxygen-enriched phase change agent. The principle and the effect of the scheme are that the nano preparation contains the oxygen-enriched phase-change agent, the oxygen-enriched phase-change agent generates micro bubbles by phase change under the HIFU focusing, the local sound field is enhanced, the required output power can be reduced on the premise of ensuring the same ablation volume, the sublethal heat stress is obviously lightened, and the heat-induced lactic acid generation is inhibited. Meanwhile, oxygen released by the oxygen-enriched phase change agent phase change can obviously improve the oxygenation level of tumors, so that the expression of HIF-1 alpha in the tumors is reduced, the transcription level of glucose transporter 1 (GLUT 1) is reduced, thereby being beneficial to reducing the generation of lactic acid, blocking the generation of lactic acid at the source, avoiding the increase of glucose uptake and the amplification of the Warburg effect caused by the rise of the level of the HIF-1 alpha due to the lack of oxygen in the tumors. The scheme combines an intervention target point with a peculiar pathological state after HIFU operation for the first time, on one hand, reduces output power required by HIFU by triggering oxygen-enriched phase change agent phase change through ultrasound, directly reduces formation of a sublethal heat stress area, blocks heat-induced lactic acid generation from upstream, which is a key link not involved in the existing la