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A kind of tumor active targeting nano-drug delivery system and preparation method thereof controlled by slightly acidic environment

An active targeting, slightly acidic environment technology, applied in antitumor drugs, pharmaceutical formulations, drug combinations, etc., to achieve the effects of improving targeting efficiency, simple preparation method, high targeting and treatment efficiency

Inactive Publication Date: 2015-10-07
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Therefore, the use of hydrophilic and negatively charged shielding molecules to modify the end of transferrin receptor-specific ligands through pH-sensitive hydrazone bonds to achieve the combination of pH-sensitivity and active targeting is expected to shield the normal tissue on the basis of active targeting. Accumulate to further improve tumor targeting; but so far, there has been no relevant report

Method used

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  • A kind of tumor active targeting nano-drug delivery system and preparation method thereof controlled by slightly acidic environment
  • A kind of tumor active targeting nano-drug delivery system and preparation method thereof controlled by slightly acidic environment
  • A kind of tumor active targeting nano-drug delivery system and preparation method thereof controlled by slightly acidic environment

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Experimental program
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Effect test

Embodiment 1

[0049] Dissolve polylysine in an appropriate amount of methanol to prepare a 10mg / ml solution, take 100μl and dry it in a vial; dissolve polyethylene glycol maleimide-polyethylene glycol 3500-succinimide in An appropriate amount of 0.035MpH 8.0 phosphate buffer solution was prepared to make a 5mg / ml working solution, and 318μl polyethylene glycol working solution was added to a vial, stirred and reacted at room temperature for 2h, and polylysine-polyethylene glycol DGL- PEG was added into a MWCO 5000 ultrafiltration centrifuge tube, purified by ultrafiltration at 12000 rpm for 30 minutes, and the unmodified carrier polylysine-polyethylene glycol DGL-PEG was obtained.

Embodiment 2

[0051] Dissolve polylysine in an appropriate amount of methanol to prepare a 10mg / ml solution, take 100μl and dry it in a vial; dissolve polyethylene glycol maleimide-polyethylene glycol 3500-succinimide in Prepare an appropriate amount of 0.035MpH 8.0 phosphate buffer solution to prepare a 5mg / ml working solution, take 318μl polyethylene glycol working solution and add it to a vial, stir and react at room temperature for 2h; then dissolve T7 in an appropriate amount of pH 7.0 phosphate buffer solution , prepared into a 1 mg / ml polypeptide solution, took 226 μl and added it to the polylysine-polyethylene glycol solution, stirred and reacted at room temperature for 24 hours, added it to a MWCO 5000 ultrafiltration centrifuge tube, purified it by ultrafiltration at 12000 rpm for 30 minutes, and obtained The carrier polylysine-polyethylene glycol-polypeptide DGL-PEG-T7 modified by targeting polypeptide T7.

Embodiment 3

[0053] Weigh 28.2 mg DGL-PEG-T7 (0.454 μmol) and 5.9 mg p-SCN-Bn-DTPA (9.08 μmol) in 12 mL PBS 9.0 for 48 hours at room temperature. The hydrazide at the end of the polypeptide T7 on the carrier can first undergo an addition reaction with the isothiocyanate on DTPA, and connect DTPA to the end of the polypeptide T7 on the carrier through an amide bond to obtain DPTD; remove unreacted p-SCN-Bn-DTPA.

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Abstract

The invention belongs to the field of biotechnology, and relates to a tumor active targeting nano drug delivery system controlled by slightly acidic environment, and a preparation method thereof. The tumor active targeting nano drug delivery system controlled by slightly acidic environment is prepared by self-assembly of a targeting peptide modified dendrimer encapsulated gene, wherein connection of the targeting peptide is realized via pH sensitive bonds using shielding molecules, and the surface of the dendrimer is rich of amino groups. According to the nano drug delivery system, because modification effect of the shielding molecules in the system, the active targeting nano drug delivery system is improved; targeting and curing efficiency are high; the preparation method is simple and convenient; and tumor cell drugs, which are derived from human or animal, and is used for targeted therapy, can be prepared.

Description

technical field [0001] The invention belongs to the field of biotechnology and relates to a drug delivery system, in particular to a tumor active targeting nanometer drug delivery system and a preparation method thereof which is controlled and activated by a slightly acidic environment. Background technique [0002] In recent years, tumor-targeted drug delivery systems have become a research hotspot in the field of anti-tumor drug delivery. There are mainly two strategies for the construction of targeted drug delivery systems: passive targeting and active targeting; the passive targeting is mainly based on the EPR effect of tumor tissue on macromolecules, while the active targeting is based on the specific binding of macromolecules. The ligands of the receptors are overexpressed on the surface of tumor cells, the drug delivery system is modified, and the specific binding properties are transferred to the drug delivery system to achieve targeted delivery. Ligand-modified nan...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K48/00A61K47/42A61P35/00
Inventor 韩亮蒋晨
Owner FUDAN UNIV
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