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Antibody-modified anti-tumor targeted drug delivery and combined treatment system as well as preparation method and application thereof

An antibody modification and combination therapy technology, applied in the field of biomedicine, can solve the problems of inability to produce PTT-chemotherapy tumor synergistic effect, polymer does not have anti-tumor efficacy, etc. Capacitive effect

Active Publication Date: 2022-07-29
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, in the prior art, polymers such as polylactic-co-glycolic acid (PLGA), polyethylene glycol (PEG), and chitosan have been combined on the surface of BPN, but traditional polymers do not have anti-tumor properties. Drug efficacy, after it is coated on the surface of BPN, it only improves the room temperature stability of BPN, and cannot produce the synergistic effect of PTT-chemotherapy tumors

Method used

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  • Antibody-modified anti-tumor targeted drug delivery and combined treatment system as well as preparation method and application thereof
  • Antibody-modified anti-tumor targeted drug delivery and combined treatment system as well as preparation method and application thereof
  • Antibody-modified anti-tumor targeted drug delivery and combined treatment system as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-5

[0057] A. Synthesis of Polymetformin:

[0058]4.0 g of polymer powder containing primary or secondary amino groups was weighed, dissolved in 100 mL of hydrochloric acid with a mass fraction of 1% under stirring, and subjected to hydrochlorination for 4 hours, and then the solution was freeze-dried to obtain hydrochloric polymer solids. Weigh 1.0 g of hydrochloric polymer solid, and dissolve it in 20 mL of 0.75% hydrochloric acid to obtain a clear solution. Weigh the solid dicyandiamide and place it in a three-necked flask, so that the mass ratio of the hydrochloride polymer solid and dicyandiamine is 1:15, and the polymer solution is added dropwise at a speed of 5-8 mL / min under stirring conditions. Add to the three-necked flask and mix well with the solid dicyandiamine. The temperature of the reaction system was rapidly raised to 100°C, and the stirring was continued until the dicyandiamine powder was completely dissolved. The temperature of the reaction system was kept con...

Embodiment 6-13

[0063] B. Preparation of black phosphorus nanosheet aqueous dispersion:

[0064] Precisely weigh a certain mass of BP solid, put it in a brown bottle and mix it with the dispersion medium, use 10 mL of dispersion medium for every 15 mg of BP solid, use a probe ultrasonic power of 200W, work for 2s, intermittently for 2s, and continue ultrasonic dispersion treatment for 24h to obtain black phosphorus nanometers. Tablets (BPN) Coarse Dispersion. The crude dispersion was centrifuged at 4000 rpm for 1 min and the supernatant was collected, and then the supernatant was removed by centrifugation at 13,000 rpm for 15 min. Add 1 / 3 volume of the above-mentioned upper liquid to the ultrapure water to resuspend the BPN precipitate at the bottom of the centrifuge tube, and use the probe ultrasonic power of 150W, work for 2s, intermittently for 2s, and continue the ultrasonic dispersion treatment of the probe for 20min to make the BPN in the ultrapure water. Completely dispersed to obtain...

Embodiment 14-23

[0069] C. Preparation of Polymetformin / Black Phosphorus Nanocomposites

[0070] Weigh a certain mass of PolyMet solid (prepared in Example 1), dissolve it with ultrapure water as a solvent, and prepare an aqueous PolyMet solution. Slowly add the PolyMet aqueous solution dropwise to the BPN aqueous dispersion (prepared in Example 6), use 100W probe ultrasonic power immediately after mixing, work for 2s, intermittently 2s, continue the probe ultrasonic dispersion pretreatment for 10min, and then continue to stir and react overnight, That is, polymetformin / black phosphorus (PolyMet / BPN) nanocomposite is obtained.

[0071] Wherein, the mass ratio of the materials used to prepare the PolyMet / BPN nanocomposite in Examples 14-23 is shown in Table 3:

[0072] The mass ratio of feeding materials: is the ratio of the absolute mass of BPN to the absolute mass of PolyMet (direct weighing) in the BPN aqueous dispersion. The absolute mass of BPN in the BPN aqueous dispersion is determined...

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Abstract

The invention relates to an antibody-modified anti-tumor targeted drug delivery and combined therapy system and a preparation method and application thereof, the system is composed of black phosphorus, polydimethyldiguanide and an anti-PD-L1 antibody, the polydimethyldiguanide wraps the surface of a black phosphorus nanosheet to form a nanocomposite, and then the anti-PD-L1 antibody is adsorbed on the surface of the nanocomposite. The black phosphorus, the polydimethyldiguanide and the anti-PD-L1 antibody used in the invention not only show the antitumor drug properties with excellent curative effects in the aspects of photothermal therapy, chemotherapy and immunotherapy, but also have the properties of carrying drugs, stabilizing drug carriers and endowing a nano drug delivery system with tumor tissue targeting, and have excellent application prospects in the field of drug excipients. In addition, the anti-tumor nano drug delivery and combined treatment system constructed by the invention cooperates with photothermal therapy, chemotherapy and immunotherapy, effectively improves the anti-tumor performance, fully avoids the potential problem of independent application of each treatment means, and excellently embodies three-in-one.

Description

technical field [0001] The invention belongs to biomedicine, and in particular relates to an antibody-modified anti-tumor targeted drug delivery and combined therapy system and a preparation method and application thereof. Background technique [0002] Malignant tumor is a disease that poses a great threat to human health, and its incidence is increasing year by year. Compared with women, breast cancer is still the most common malignant tumor. Chemotherapy is one of the most commonly used methods in the treatment of breast cancer. Chemotherapy drugs can directly kill tumor cells, but conventional chemotherapy has problems such as poor targeting, large side effects, and easy generation of drug resistance after repeated administration, so chemotherapy drugs alone often end in failure. Photothermal therapy is an emerging and promising anti-tumor treatment modality, which utilizes photothermal materials with high photothermal conversion efficiency to convert light energy into ...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K31/785A61K39/395A61K47/52A61K47/69A61P35/00A61P35/04C08G73/00
CPCA61K41/0052A61K31/785A61K39/3955A61K47/52A61K9/0019A61K47/6929A61P35/00A61P35/04C08G73/00A61K2300/00
Inventor 王伟梅逸君
Owner CHINA PHARM UNIV
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