Tumor therapeutic nanomedicine targeting trop2 protein on tumor cell surface and preparation method thereof
A nano drug and drug technology, applied in the direction of antineoplastic drugs, drug combination, drug delivery, etc., to achieve the effect of improving the therapeutic effect, prolonging the duration of action, and improving the utilization rate
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Embodiment 1
[0063] Acquisition and Analysis of Uc003xsl.1
[0064] 1. Acquisition of Uc003xsl.1
[0065] The inventors of the present application collected 6 fresh breast cancer tissues from the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, including 3 TNBC and 3 Luminal breast cancer tissues. Then lncRNA sequencing was carried out by Illumina PE150 to analyze the expression of lncRNA in 6 fresh tissues of breast cancer, the sequencing heat map is as follows figure 1 As shown in A (left), 30 lncRNAs whose expression levels in TNBC tissues were up-regulated compared with Luminal tissues were screened out.
[0066] At the same time, in order to find out the biomarkers associated with TNBC metastasis, the inventors constructed a breast cancer lung metastasis model, collected highly metastatic MDA-MB-231 cells from the lung metastases of mice, and screened out the metastatic MDA-MB-231 cells by lncRNA sequencing. -MB-231 cells express 267 lncRNAs up-regulated compared with ordina...
Embodiment 2
[0075] Synthesis and structure analysis of PDSA
[0076] 1. Synthesis of PDSA
[0077] PDSA in this example is a high molecular polymer decomposed at a higher glutathione concentration. In this example, the "one-pot method" is used for large-scale preparation. The preparation process includes: (1) the fat Acid and triethylamine are mixed and dissolved, and the fatty diacids include succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, undecanedioic acid, dodecanedioic acid, For all fatty diacids such as carbolic acid or tridecanedioic acid, the solvent used for mixing and dissolving is a strong polar solvent such as dimethylsulfoxide or dimethylformamide;
[0078] (2) Add Cystine dimethyl esterdihydrochloride dropwise to the mixed solution of fatty diacid and triethylamine under the condition of ice-salt bath. Then, after stirring the reaction at room temperature for 15 minutes to 4 hours, the precipitate in the reaction system wa...
Embodiment 3
[0083] Detection of Trop2 expression in breast cancer
[0084] 1. Gene expression detection of Trop2 in different breast cell lines
[0085] The inventors based on normal mammary epithelial cell lines: MCF10A, HMEC; TNBC cell lines: MDA-MB-231, MDA-MB-436, MDA-MB-468, BT549; HER2+ breast cancer cell lines BT474, SKBR3; Luminal mammary gland Cancer cell lines T47D, MCF-7 and ZR751 were tested for Trop2 gene expression levels in different cells. The detection method was Western blot, and the detection results were as follows: Figure 9 As shown, it was found that Trop2 was highly expressed in breast cancer cell lines than normal breast epithelial cell lines MCF10A and HMEC, and the expression levels in TNBC cell lines MDA-MB-231, MDA-MB-436, MDA-MB-468 and BT549 The highest expression level was in HER2+ breast cancer cell lines BT474 and SKBR3, and the lowest expression level was in Luminal breast cancer cell lines T47D, MCF-7 and ZR751. The above results also indicate that the ...
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