Antitumor compound preparation integrating targeting photothermal therapy and immunological therapy as well as preparation method and application of antitumor compound preparation

A photothermal therapy and immunotherapy technology, applied in anti-tumor drugs, carrier-binding antigen/hapten components, drug combinations, etc., can solve the problem of time-consuming waiting, unsatisfactory effects of malignant tumor growth and development, and immunotherapy playing a role Long cycle and other problems, to achieve the effect of improving stability, good passive tumor targeting, and good chemical stability

Active Publication Date: 2017-01-04
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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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  • Antitumor compound preparation integrating targeting photothermal therapy and immunological therapy as well as preparation method and application of antitumor compound preparation
  • Antitumor compound preparation integrating targeting photothermal therapy and immunological therapy as well as preparation method and application of antitumor compound preparation
  • Antitumor compound preparation integrating targeting photothermal therapy and immunological therapy as well as preparation method and application of antitumor compound preparation

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Experimental program
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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 invention relates to an antitumor compound preparation integrating targeting photothermal therapy and immunological therapy as well as a preparation method and an application of the antitumor compound preparation. The antitumor compound preparation comprises components of Cypate lipidosome, ADM-BSA (adriamycin-bovine serum albumin) and HA-ADM (hyaluronic acid-adriamycin). After Cypate is subjected to entrapment with lipidosome, the chemical stability is remarkably superior to that of free Cypate, the in-vitro warming effect is better, and good tumor targeting performance and photothermal therapy effect are realized; the Cypate lipidosome has good targeting performance and better photothermal therapy effect and constitutes a dual-targeting HA-hapten immunological preparation integrating the immunological therapy and the active targeting chemotherapy through combination of ADM-BSA and HA-ADM, and the preparation has a good therapeutic effect on deep residues and metastasized tumor cells, can overcome defects of respective therapy and realizes collaborative therapy.

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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IPC IPC(8): A61K41/00A61K47/48A61K39/385A61K31/704A61K9/127A61P35/00
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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