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Targeted photothermal therapy combined with immunotherapy anti-tumor compound preparation and its preparation method and application

A technology of photothermal therapy and immunotherapy, applied in the direction of antineoplastic drugs, carrier-bound antigen/hapten components, drug combinations, etc. Time waiting and other issues, to achieve good passive targeting of tumors, good chemical stability, and improved stability

Active Publication Date: 2019-06-21
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although many studies have shown that both cellular immunity and humoral immunity in the body generate immune responses to tumor cells, due to the long period of immunotherapy, it takes time to start the growth inhibitory effect on tumor cells, so it can inhibit the growth and development of malignant tumors. The effect is not ideal

Method used

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  • Targeted photothermal therapy combined with immunotherapy anti-tumor compound preparation and its preparation method and application
  • Targeted photothermal therapy combined with immunotherapy anti-tumor compound preparation and its preparation method and application
  • Targeted photothermal therapy combined with immunotherapy anti-tumor compound preparation and its preparation method and application

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Experimental program
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Effect test

Embodiment 1

[0054] The investigation of the preparation and physicochemical property of embodiment one Cypate liposome

[0055] Weigh 10g of phospholipids, 2.5g of cholesterol and 0.5g of Cypate into a vial, add 3.75mL of absolute ethanol and 1.25mL of ethyl acetate, seal it, and put it in a water bath at 50°C for 1250 r min -1 Stir for 5 min and sonicate for 1 min to fully dissolve it. Quickly and evenly add 430g of purified water under stirring condition, 50℃ water bath 1250 r min -1 Stir for 5 minutes to emulsify, sonicate for 1 minute, and continue stirring for 15 minutes to make the emulsification complete. Open the lid and put it in a 37°C water bath at 750 r min -1 Stir for 5 hours, completely volatilize the organic solvent, and obtain the Cypate liposome suspension.

[0056] The prepared Cypate liposomes have good uniformity, and the shape is regular spherical, and the apparent morphology of Cypate liposomes observed by a transmission electron microscope (TEM) is spherical and e...

Embodiment 2

[0066] Example 2 Synthesis of Immunogen BSA-ADM and Preparation of Antibody

[0067] Doxorubicin is a small molecule with only immunoreactivity but no immunogenicity. It cannot directly immunize animals to produce antibodies. It needs to be coupled with heterologous proteins (mostly bovine serum albumin, BSA) to prepare immunogens. In addition, in the enzyme-linked immunosorbent assay (ELISA) method, the antibody is bound to the coated antigen on the microtiter plate, and doxorubicin is often combined with another variant protein (multipurpose ovalbumin, OVA).

[0068] Synthetic immunogen ADM-BSA and coating agent ADM-OVA were prepared by glutaraldehyde cross-linking method. The preparation process is as follows: Weigh 100 mg of BSA into a 25 mL round bottom flask, add 5 mL of 0.1 mol . L -1 PBS solution, fully dissolved, stirring at 10 r . min -1 , another 40.0 mg ADM . HCl was dissolved in 3.0 mL DMF and PBS mixed solution (DME:PBS=1:1), ADM was added dropwise to the BS...

Embodiment 3

[0086] The synthesis of embodiment three HA-ADM

[0087] The synthetic route is as follows:

[0088] (1) Activation of hyaluronic acid: Weigh 42.07 mg of hyaluronic acid (HA) into a 10 mL round bottom flask, add 2.0 mL of purified water, fully dissolve, and stir at 120 r min -1 , another 38.3 mg EDC and 22.9 mg NHS were added sequentially, and reacted for 8 hours under dark conditions, 8000 r min -1 After centrifugation for 10 min, the supernatant was collected, which was the activated HA solution.

[0089] (2) Synthesis of HA-ADM: take 10.8 mg ADM . After HCl was dissolved in 1.3 mL of purified water, it was added dropwise to the above activated HA solution, 120 r min -1 , and react in the dark at 25°C for 12 h. 8000 rpm -1 Centrifuge for 10 min to take the supernatant, put it in a dialysis bag with a molecular cut-off of 8000-14000, use 1000 mL purified water as the receiving solution, dialyze, change the receiving solution every 24 hours, after the dialysis is complete...

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Abstract

The present invention relates to a targeted photothermal therapy combined with immunotherapy anti-tumor compound preparation and its preparation method and application, which consists of Cypate liposome, Adriamycin-Bovine Serum Albumin (ADM-BSA) and hyaluronic acid-Adriamycin element (HA‑ADM) composition. The chemical stability of Cypate entrapped in liposomes is significantly better than that of free Cypate, and the in vitro heating effect is stronger, and it has good tumor targeting and photothermal therapy effects. Cypate liposome has good targeting and has strong photothermal therapy effect. Combining ADM‑BSA and HA‑ADM constitutes a dual-targeted hyaluronic acid‑hapten immune preparation for immunotherapy and active targeted chemotherapy. The treatment effect of residual and metastatic tumor cells is good, which can avoid the defects of each treatment and achieve the purpose of synergistic treatment.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a targeted photothermal therapy combined with immunotherapy anti-tumor compound preparation and its preparation method and application. Background technique [0002] The threat of cancer to human beings is increasing day by day, and the recurrence and metastasis of cancer are still problems that traditional treatment methods still need to face. Therefore, it is necessary to find newer and more comprehensive treatment methods. Traditional surgical treatment, radiotherapy and chemotherapy have the disadvantages of possible damage to normal tissues of the body and other side effects, which limit their therapeutic effect on cancer. In recent years, photothermal therapy (PTT), which uses near-infrared photothermal conversion, has rapidly developed into another new tumor treatment technology after traditional chemotherapy, radiotherapy, and surgery. The basic principle ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K41/00A61K47/61A61K47/62A61K39/385A61K31/704A61P35/00
CPCA61K39/0013A61K39/385A61K41/0052A61K9/127A61K31/704A61K47/61A61P35/00A61K2300/00
Inventor 杨红刘迪陈华兵邓安平吕小燕王雪李明姚枫枫付佩徐新早徐涛
Owner SUZHOU UNIV
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