Drug-loaded ATP-sensitive liposome with tumor near-infrared fluorescence imaging function and preparation method thereof

Abstract

The invention relates to an ATP sensitive liposome with a tumor near infrared fluorescence development effect and a treatment effect. ATP sensitive nucleotide double strands loaded with adriamycin are encapsulated into a liposome dimolecular layer membrane coupled with tumor target polypeptide, so that a nanovesicle is formed, the ATP sensitive nucleotide double strands are formed by self-assembling of ATP sensitive nucleotide single strand coupled with fluorescent dye and ATP sensitive nucleotide complementary single strands coupled with a fluorescence quenching agent according to a base complementarity pairing principle, and the liposome dimolecular layer membrane coupled with the tumor target polypeptide consists of polyethylene glycol phosphatidyl ethanolamine coupled by the tumor target polypeptide, phosphatide and cholesterol. The invention further provides a preparation method of the liposome. The liposome concurrently has an active tumor targeting property, an ATP sensitive fluorescence emitting function, a medicine release switching function and an in vivo long-circulating function, the purpose of combining function like tumor near infrared fluorescence development, tumor diagnosis and tumor treatment in the same liposome is achieved, and besides, the preparation technology is simple and easy to operate.

Description

technical field

[0001] The invention belongs to the field of tumor diagnosis and treatment, and in particular relates to a drug-loaded ATP-sensitive liposome with the function of tumor near-infrared fluorescence imaging and a preparation method thereof. Background technique

[0002] Tumor has become a major disease that threatens human health. At present, when the tumor is diagnosed, the vast majority of cancer patients are in the middle and advanced stages, and the treatment methods mainly include surgery, radiotherapy, and chemotherapy. However, patients with advanced tumors are prone to recurrence, drug resistance, metastasis and complications after treatment, which are the main reasons for treatment failure and patient death. The "nano diagnosis and treatment system" developed in recent years integrates diagnosis and treatment on the same nanoprobe, and realizes high-sensitivity detection and minimally invasive / non-invasive treatment of tumors at the same time, with sim...

Examples

Embodiment 1

[0048] The preparation method of the drug-loaded ATP-sensitive liposome with tumor near-infrared fluorescence imaging function described in this embodiment is as follows:

[0049] (1) Dissolve cRGD-Cys and distearoylphosphatidylethanolamine-polyethylene glycol 2000-maleamide (DSPE-PEG2000-Mal) in a molar ratio of 1:1 in methanol to obtain a mixed solution. The amount of methanol used is The molar concentration of DSPE-PEG2000-Mal in the mixed solution is 1mmol / L. The resulting mixed solution was magnetically stirred at room temperature for 12 hours to react, and after the reaction was completed, the solvent in the reaction solution was removed by rotary evaporation under reduced pressure to obtain the distearoylphosphatidylethanolamine-polyethylene glycol 2000 ( cRGD-DSPE-PEG2000);

[0050] (2) Dissolve cRGD-DSPE-PEG2000, lecithin and cholesterol prepared in step (1) in a molar ratio of 5:65:35 in a composite solvent obtained by mixing chloroform and methanol at a volume rati...

Embodiment 2

[0060] The preparation method of the drug-loaded ATP-sensitive liposome with tumor near-infrared fluorescence imaging function described in this embodiment is as follows:

[0061] (1) Dissolve Her2-cys and dimyristoylphosphatidylethanolamine-polyethylene glycol 2000-maleamide (DMPE-PEG2000-Mal) in methanol at a molar ratio of 1:1 to obtain a mixed solution. The amount of methanol used is The molar concentration of DMPE-PEG2000-Mal in the mixed solution is 10mmol / L. The resulting mixed solution was magnetically stirred at room temperature for 24 hours to react, and after the reaction was completed, the solvent in the reaction solution was removed by rotary evaporation under reduced pressure to obtain Her2-coupled dimyristoylphosphatidylethanolamine-polyethylene glycol 2000 (Her2- DMPE-PEG2000);

[0062] (2) dissolving Her2-DMPE-PEG2000 prepared in step (1), soybean lecithin and cholesterol in a molar ratio of 2:78:20 in a composite solvent obtained by mixing chloroform and met...

Embodiment 3

[0067] The preparation method of the drug-loaded ATP-sensitive liposome with tumor near-infrared fluorescence imaging function described in this embodiment is as follows:

[0068] (1) Her2-cys and dipalmitoylphosphatidylethanolamine-polyethylene glycol 2000-maleamide (DPPE-PEG2000-Mal) are dissolved in methanol at a molar ratio of 1:1 to obtain a mixed solution, and the amount of methanol is as described The molar concentration of the mixed solution DPPE-PEG2000-Mal is 5mmol / L. The resulting mixed solution was magnetically stirred at room temperature for 16 hours to react, and after the reaction was completed, the solvent in the reaction solution was removed by rotary evaporation under reduced pressure to obtain Her2-coupled dipalmitoylphosphatidylethanolamine-polyethylene glycol 2000 (Her2-DPPE -PEG2000);

[0069] (2) dissolving Her2-DMPE-PEG2000 prepared in step (1), soybean lecithin and cholesterol in a molar ratio of 8:42:50 in a composite solvent obtained by mixing chlor...

technical field

[0001] The invention belongs to the field of tumor diagnosis and treatment, and in particular relates to a drug-loaded ATP-sensitive liposome with the function of tumor near-infrared fluorescence imaging and a preparation method thereof. Background technique

[0002] Tumor has become a major disease that threatens human health. At present, when the tumor is diagnosed, the vast majority of cancer patients are in the middle and advanced stages, and the treatment methods mainly include surgery, radiotherapy, and chemotherapy. However, patients with advanced tumors are prone to recurrence, drug resistance, metastasis and complications after treatment, which are the main reasons for treatment failure and patient death. The "nano diagnosis and treatment system" developed in recent years integrates diagnosis and treatment on the same nanoprobe, and realizes high-sensitivity detection and minimally invasive / non-invasive treatment of tumors at the same time, with sim...

Examples

Embodiment 1

[0048] The preparation method of the drug-loaded ATP-sensitive liposome with tumor near-infrared fluorescence imaging function described in this embodiment is as follows:

[0049] (1) Dissolve cRGD-Cys and distearoylphosphatidylethanolamine-polyethylene glycol 2000-maleamide (DSPE-PEG2000-Mal) in a molar ratio of 1:1 in methanol to obtain a mixed solution. The amount of methanol used is The molar concentration of DSPE-PEG2000-Mal in the mixed solution is 1mmol / L. The resulting mixed solution was magnetically stirred at room temperature for 12 hours to react, and after the reaction was completed, the solvent in the reaction solution was removed by rotary evaporation under reduced pressure to obtain the distearoylphosphatidylethanolamine-polyethylene glycol 2000 ( cRGD-DSPE-PEG2000);

[0050] (2) Dissolve cRGD-DSPE-PEG2000, lecithin and cholesterol prepared in step (1) in a molar ratio of 5:65:35 in a composite solvent obtained by mixing chloroform and methanol at a volume rati...

Embodiment 2

[0060] The preparation method of the drug-loaded ATP-sensitive liposome with tumor near-infrared fluorescence imaging function described in this embodiment is as follows:

[0061] (1) Dissolve Her2-cys and dimyristoylphosphatidylethanolamine-polyethylene glycol 2000-maleamide (DMPE-PEG2000-Mal) in methanol at a molar ratio of 1:1 to obtain a mixed solution. The amount of methanol used is The molar concentration of DMPE-PEG2000-Mal in the mixed solution is 10mmol / L. The resulting mixed solution was magnetically stirred at room temperature for 24 hours to react, and after the reaction was completed, the solvent in the reaction solution was removed by rotary evaporation under reduced pressure to obtain Her2-coupled dimyristoylphosphatidylethanolamine-polyethylene glycol 2000 (Her2- DMPE-PEG2000);

[0062] (2) dissolving Her2-DMPE-PEG2000 prepared in step (1), soybean lecithin and cholesterol in a molar ratio of 2:78:20 in a composite solvent obtained by mixing chloroform and met...

Embodiment 3

[0067] The preparation method of the drug-loaded ATP-sensitive liposome with tumor near-infrared fluorescence imaging function described in this embodiment is as follows:

[0068] (1) Her2-cys and dipalmitoylphosphatidylethanolamine-polyethylene glycol 2000-maleamide (DPPE-PEG2000-Mal) are dissolved in methanol at a molar ratio of 1:1 to obtain a mixed solution, and the amount of methanol is as described The molar concentration of the mixed solution DPPE-PEG2000-Mal is 5mmol / L. The resulting mixed solution was magnetically stirred at room temperature for 16 hours to react, and after the reaction was completed, the solvent in the reaction solution was removed by rotary evaporation under reduced pressure to obtain Her2-coupled dipalmitoylphosphatidylethanolamine-polyethylene glycol 2000 (Her2-DPPE -PEG2000);

[0069] (2) dissolving Her2-DMPE-PEG2000 prepared in step (1), soybean lecithin and cholesterol in a molar ratio of 8:42:50 in a composite solvent obtained by mixing chlor...

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