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Nanometer delivery system capable of promoting permeation, relieving tumor hypoxia and targeting tumor cells as well as preparation method and application of nanometer delivery system

A nano-carrier and cell membrane technology, applied in the field of medicine, to achieve the effects of protective activity, large specific surface area, and good drug-loading capacity

Active Publication Date: 2022-04-01
中国人民解放军海军军医大学第一附属医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005]The cell membrane biomimetic nano-drug delivery system combines the transformability of nano-carriers with the natural functions of cell membranes, so that the system has both physical and chemical properties that can be adjusted according to the application Nanoparticles, which inherit the complex functions of cell membranes, can protect collagenase from being degraded in the blood circulation by coating with biomimetic membranes, and can also take advantage of the targeting advantages of biomimetic membranes. Tumor therapy provides a novel, highly efficient and low toxicity nano drug delivery system

Method used

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  • Nanometer delivery system capable of promoting permeation, relieving tumor hypoxia and targeting tumor cells as well as preparation method and application of nanometer delivery system
  • Nanometer delivery system capable of promoting permeation, relieving tumor hypoxia and targeting tumor cells as well as preparation method and application of nanometer delivery system
  • Nanometer delivery system capable of promoting permeation, relieving tumor hypoxia and targeting tumor cells as well as preparation method and application of nanometer delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Example 1: MP@H-MnO 2 -Synthesis of Dox-Col nanoparticles

[0058] Refer to the method of Chinese invention patent CN201710618202.6 to synthesize mesoporous manganese dioxide, followed by collagenase modification and pH-sensitive fusion membrane coating and doxorubicin drug loading, the results of average particle size and potential see figure 2 , image 3 ), see the electron micrograph Figure 4 , the particle size results are consistent with the TEM image, MP@H-MnO 2 -Dox-Col nanoparticles particle size is about 220nm.

Embodiment 2

[0059] Example 2: MP@H-MnO 2 -Study on the Stability of Dox-Col Nanoparticles

[0060] H-MnO 2 -Dox NPs and MP@H-MnO 2 -Dox-Col NPs were resuspended in PBS, and the particle size of the sample was measured by DLS within 15 days to investigate the stability of NPs. see results Figure 5 , MP@H-MnO 2 -Dox-Col NPs and H-MnO 2 -Dox NPs maintained good stability during the 2-week study period.

Embodiment 3

[0061] Embodiment 3: The release investigation of Dox under different conditions

[0062] Evaluation of MP@H-MnO by Dialysis Bag Method 2 - Release of doxorubicin from Dox-Col NPs with or without 100 μM hydrogen peroxide at pH=7.4 or pH=6.5, respectively. 2 ml of MP@H-MnO 2 -Dox-Col NPs were placed in dialysis bags (MWCO=3500Da), respectively immersed in 50 ml of different external fluids, stirred at 37.0°C and 100 rpm. Take 1ml of the solution at 0.5, 1, 2, 3, 4, 5, 10, 15, 20, and 25 hours respectively, measure the absorbance with UV-Vis spectrophotometry, and replace it with an equal volume of release solution. Draw in vitro release curves.

[0063] Such as Figure 6 shown in H 2 o 2 and pH 6.5, MP@H-MnO 2 The amount of Dox released by -Dox-Col NPs within 15h gradually reached >70% (p2-Dox-Col NPs can be based on tumor site H + and H 2 o 2 The characteristics of "on-demand" drug release.

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Abstract

The invention relates to the technical field of medicines, in particular to a nano delivery system capable of promoting permeation, relieving tumor hypoxia and targeting tumor cells as well as a preparation method and application of the nano delivery system. The nano delivery system provided by the invention takes mesoporous manganese dioxide as a basis, the mesoporous manganese dioxide can be used as a carrier to load a hydrophobic therapeutic drug, and meanwhile, the specific catalytic property of manganese dioxide can promote hydrogen peroxide at a tumor site to generate oxygen so as to relieve an anoxic state at the tumor site; collagenase can be grafted on the surface of the carrier to decompose a tumor extracellular matrix to promote permeation, and finally the surface of the carrier is coated with a membrane fused by the pH-sensitive lipidosome and a macrophage membrane to achieve the purposes of targeting and responding to a tumor microenvironment. A novel nano delivery system is provided for drug delivery, tumor cells can be targeted, the tumor microenvironment can be responded, collagenase is intelligently protected and exposed to play a permeation promoting role, and the nano delivery system is efficient, low in toxicity and accurate.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a nano-delivery system capable of promoting penetration, alleviating tumor hypoxia and targeting tumor cells, its preparation method and application. Background technique [0002] Tumor is one of the most common causes of morbidity and death in humans at present. The current treatment methods for tumor mainly include chemotherapy, radiotherapy and so on. Hypoxia is a prominent feature of solid tumors. The hypoxic microenvironment exacerbates the malignancy of tumors and reduces the sensitivity of tumors to various treatments, such as chemotherapy, radiotherapy, photodynamic therapy, etc., resulting in poor prognosis of patients. On the one hand, due to the chaotic vascular structure in the central area of ​​the tumor, some areas cannot supply oxygen through blood circulation; Therefore, tumor oxygen supply intervention to enhance tumor therapy has attracted extensive attention...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/46A61K47/42A61K47/02A61K31/704A61P35/00
Inventor 高申李鹃鹃宫春爱韩治敏台宗光丁楠陈昕璐郭欢欢杨婷
Owner 中国人民解放军海军军医大学第一附属医院
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