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Dopamine ligand-containing diblock polymer, and synthesis method and application thereof

A technology of block polymers and dopamine, which is applied in the fields of biomedical technology, nanomedicine and new materials, can solve the problems that PEG shells are unfavorable for tumor cell endocytosis and difficult for antitumor drugs, and achieve strong inhibitory activity and simple preparation method , enhance the effect of endocytosis

Active Publication Date: 2019-08-09
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In addition, traditional nano-drug delivery systems usually use polyethylene glycol (PEG) as a hydrophilic segment to improve the long-term circulation ability of the nano-system, but the existence of the PEG shell is also not conducive to tumor cell endocytosis, and anti-tumor drugs are difficult to Sufficient dose reaches the target located in the cell

Method used

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  • Dopamine ligand-containing diblock polymer, and synthesis method and application thereof
  • Dopamine ligand-containing diblock polymer, and synthesis method and application thereof
  • Dopamine ligand-containing diblock polymer, and synthesis method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0037] Synthesis of Macromolecular Initiator PBA-PEG

[0038] (1) Synthesis of PBA-COOH targeting group

[0039] Dissolve 2.5g of m-aminophenylboronic acid (18mmol) and 5g of succinic anhydride (50mmol) in 15mL of pyridine, and react at room temperature. After reacting for 4 hours, spin the solvent, add 1M NaOH aqueous solution to dissolve the solid, and then add 1M hydrochloric acid to adjust the pH To 3.0, a solid gradually precipitated out. After filtration, 3.6 g of brown solid PBA-COOH was obtained with a yield of 84%.

[0040] The structure of the PBA-COOH is shown in formula (1).

[0041]

[0042] Formula 1).

[0043] (2) Synthesis of PBA-PEG macroinitiator

[0044] PBA-COOH (237mg, 1mmol), EDCI (288mg, 1.5mmol) and NHS (173mg, 1.5mmol) were dissolved in dichloromethane, and 4g of bisaminopolyethylene glycol was added and stirred at room temperature for 12h. The reaction solution was precipitated three times with glacial ether, and the solid obtained by filtrati...

Embodiment 2

[0049]Synthesis of Diblock Polymer PBA-PEG-P(Glu-co-GluDA) Containing Dopamine Ligand

[0050] (1) Synthesis of PBA-PEG-PBLG

[0051] The macroinitiator PBA-PEG (2g, 0.5mmol) and (2g, 7.5mmol) polymerized monomer 5-benzyl ester-L-glutamic acid-N-carboxyl ring acid anhydride were dissolved in DMF, reacted at room temperature for 48h, and reacted The solution was precipitated three times with glacial ether, and the solid obtained by filtration was dialyzed with deionized water for 24 hours to obtain a white solid PBA-PEG-PBLG with a yield of 81%.

[0052] Described PBA-PEG-PBLG structure is shown in formula (3)

[0053]

[0054] Formula (3), wherein m=15.

[0055] (2) Dissolve 1g of PBA-PEG-PBLG and 1.4mL of methyl phenyl sulfide in 12mL of trifluoroacetic acid, add 1.2mL of trifluoromethanesulfonic acid dropwise under ice-cooling, stir for 1h, then raise to room temperature and continue the reaction for 1.5h , the reaction solution was precipitated three times with glacia...

Embodiment 3

[0065] Preparation of core-crosslinked empty micelles

[0066] (1) Preparation of uncrosslinked empty micelles: Weigh 10 mg of PBA-PEG-P(Glu-co-GluDA) having the structure of formula (I) (wherein, in formula I, x=10, y=5), Dissolve in 1 mL of analytically pure dimethyl sulfoxide, add dropwise to 10 mL of ultrapure water with a stirring speed of 500 r / min, continue stirring for 0.5 h, filter the resulting mixed solution with a needle filter of 0.45 Bm, and then dialyze for 48 h every 6 h Change the ultrapure water) to remove the organic solvent.

[0067] (2) Cross-linking of empty micelles: 111 μL of 40 mM ferric chloride aqueous solution was added to the uncross-linked nano-micelle solution, stirring was continued at room temperature for 1 h, and then the pH was adjusted to 7.4. Subsequent dialysis removes uncomplexed iron ions. The dialyzed solution was freeze-dried to obtain core-crosslinked empty micelles.

[0068] Such as image 3 As shown, the average particle size of...

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Abstract

The invention discloses a dopamine ligand-containing diblock polymer, and a synthesis method and an application thereof. The polymer uses polyethylene glycol as a hydrophilic end and phenylboronic acid-modified polyethylene glycol as a targeting ligand, and uses glutamic acid and glutamic acid-dopamine as the hydrophobic end of a repeating unit. The dopamine ligand-containing diblock polymer prepared in the invention can be used for encapsulating doxorubicin to form drug-loaded nanomicelles, then iron ions are added, and the drug-loaded nanomicelles are crosslinked through coordination bonds formed between dopamine and the iron ions in order to form core-crosslinked doxorubicin-loaded nanomicelles. The core-crosslinked micelles prepared in the invention has the advantages of simple preparation method, high drug encapsulation rate, keeping stable during blood circulation, and realization of the release of pH-sensitive drugs in tumor cell lysosomes.

Description

technical field [0001] The invention belongs to the fields of biomedical technology, nanomedicine and new materials, and specifically relates to the synthesis of a two-block polymer containing a dopamine ligand and an intelligent nanoglue applied to enhance tumor cell uptake and drug release controlled by tumor cell lysosome pH bundle carrier. Background technique [0002] Although traditional chemotherapeutic drugs have achieved great success in tumor treatment, many of their limitations have limited the further improvement of clinical efficacy, such as serious side effects, poor selectivity, and tumor cells are prone to drug resistance to them. The intelligent nano drug delivery system provides an effective way to realize the precise treatment of chemotherapy drugs and reduce the side effects. Taking advantage of the high penetration and long retention effect (EPR effect) of solid tumors, the intelligent nano-drug delivery system can be enriched in tumor tissue, and at th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G65/333A61K9/107A61K47/34A61K31/704A61P35/00
CPCA61K9/1075A61K31/704A61K47/34A61P35/00C08G65/33396
Inventor 余家会黄钰淑徐艳昀伍彦仟尤东磊
Owner EAST CHINA NORMAL UNIV
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