Antibody nanoparticles coated by red cell membranes for antibody drug delivery and preparation method

A technology of nanoparticles and red blood cell membranes, which is applied in the direction of antibodies, drug combinations, anti-tumor drugs, etc., can solve the problems of the difficulty of excreting macromolecular PEG, high selectivity of modified molecules, and insufficient purity of products, etc., and prolong the time of circulation in the body , low clearance rate, high cancer cell uptake effect

Active Publication Date: 2016-07-20
EAST CHINA NORMAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, PEGylation has become the gold standard for increasing circulation time, but there are also some problems, such as insufficient product purity, high selectivity for modified molecules, possible increase in drug toxicity, and difficulty in excreting large molecular PEGs from the body, etc.

Method used

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  • Antibody nanoparticles coated by red cell membranes for antibody drug delivery and preparation method
  • Antibody nanoparticles coated by red cell membranes for antibody drug delivery and preparation method
  • Antibody nanoparticles coated by red cell membranes for antibody drug delivery and preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Preparation of Anti-hTERT Monoclonal Antibody Nanoparticles

[0028] Put the anti-hTERT monoclonal antibody raw material into a 10kD dialysis bag, dialyze in ultrapure water, change the water after 2h and 4h, and dialyze overnight. The antibodies in the dialysis bag were collected, freeze-dried, and stored at -20°C. Take 3mg of lyophilized antibody, dissolve it in 0.5mL of 0.01N HCl containing 0.2% Tween80, add 0.01NNaOH dropwise under magnetic stirring, until the smoke-like precipitation that appears reaches the maximum amount. Centrifuge at 6500rpm for 5 minutes, carefully remove the supernatant to obtain anti-hTERT monoclonal antibody nanoparticles.

Embodiment 2

[0030] Preparation of Anti-hTERT Monoclonal Antibody Nanoparticles Wrapped in Erythrocyte Membrane

[0031] After the SD rats were fully anesthetized with 2% pentobarbital sodium solution, the xiphoid process and the above parts were cut open, and after the heart was exposed, a needle was inserted from the left ventricle, and 1 mL of blood was collected from a syringe washed with 0.5% heparin sodium. The blood was transferred to a 2m EP tube containing sodium heparin. Put the whole blood in a 4°C centrifuge at 900g for 20min, discard the supernatant, leave a dark red precipitate, take 3 times the volume of the precipitate in 1*PBS, blow it evenly, and put it in a 4°C centrifuge for centrifugation 2500g, 15min, this is the first washing. Put it into a centrifuge and centrifuge at 2500g for 15min, which is the second washing. Repeat the above steps again, this is the third wash. Discard the supernatant, leave the precipitate, take the same amount of 1*PBS as the precipitate a...

Embodiment 3

[0033] The particle size distribution of embodiment 3 nanoparticles

[0034] Using the prepared anti-hTERT monoclonal antibody nanoparticles wrapped in the red blood cell membrane, the particle size distribution was detected by DLS, and the results can be found in figure 2 .

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Abstract

The invention discloses antibody nanoparticles coated by natural red cell membranes for antibody drug delivery and a preparation method of the antibody nanoparticles. The red cell membranes in the invention are extracted from experimental rats, most of the contents and unrelated proteins are removed after the red cell membranes are treated, and protein nanoparticles formed by antibodies are coated with the obtained red cell membranes. The method is suitable for coating nanoparticles formed by different antibodies through the red cell membranes, can improve the stabilities and the in-vivo circulation times of free antibodies, and further reduces the body immunity clearance rate.

Description

technical field [0001] The invention relates to the technical field of antibody drugs and nanomedicine, in particular to an antibody nanoparticle coated with red blood cell membrane for delivery of antibody drugs and a preparation method thereof. Background technique [0002] Compared with traditional small molecule anticancer drugs, antibodies are increasingly becoming one of the most important anticancer drugs due to their high specificity and strong affinity. In contrast, although small molecule anticancer drugs have certain efficacy and are still widely used in chemotherapy, they still have disadvantages such as non-specific toxicity (due to targeting all differentiated cells) and small therapeutic window. In addition, the drug resistance of small molecule anticancer drugs is also a common problem in their clinical use. These shortcomings have brought a lot of pain to chemotherapy patients. Antibodies have attracted more and more attention because of their low non-speci...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/46A61K39/395A61P35/00
CPCA61K9/5176A61K2039/505A61K2039/585C07K16/40
Inventor 王依婷丁晓铃汉琳孙磊闫志强朱建中王镜俞磊
Owner EAST CHINA NORMAL UNIV
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