Adriamycin-indocyanine green bionic nanoparticles and application thereof

A technology of indocyanine green and biomimetic nanometer, applied in nanotechnology, nanotechnology, nanomedicine, etc.

Active Publication Date: 2020-04-14
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there are no reports on nanoparticles that kill circulating tumor cells and exosomes, cut off the connection between exosomes and immune cells, and improve the immunosuppressive tumor microenvironment

Method used

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  • Adriamycin-indocyanine green bionic nanoparticles and application thereof
  • Adriamycin-indocyanine green bionic nanoparticles and application thereof
  • Adriamycin-indocyanine green bionic nanoparticles and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0107] Example 1: Synthesis and Characterization of Doxorubicin-Indocyanine Green Biomimetic Nanoparticles Coated with Platelet Membrane

[0108] AuDIs as the inner core were obtained by using gold nanocages (0.1 mg mL -1 ) and DOX (0.05mg mL -1 ) and ICG (0.05mg mL -1 ) were prepared by incubating with stirring at room temperature for 36 hours. The final mixture was centrifuged at 16000 g for 25 min and washed with PBS to remove residues of DOX and ICG. Similar treatment was used to prepare AuDs or AuIs with / without DOX or ICG.

[0109] After platelet-rich plasma was anticoagulated with EDTA, red blood cells were removed by centrifugation at 100g for 20 minutes, the supernatant was added to prostacyclin to inhibit platelet activation, centrifuged at 800g for 20 minutes, and resuspended in PBS containing protease inhibitors. Platelet membranes were prepared by repeated freezing and thawing. Platelets were quickly frozen in liquid nitrogen and dissolved at room temperature...

Embodiment 2

[0113] Example 2: Effects of PNMAuDIs on 4T1 cells

[0114] Confocal microscopy was used to examine cellular internalization of PNMAuDIs. 4T1 cells were incubated with PNMAuDIs, NMAuDIs, PMAuDIs, ICG and DOX with / without laser irradiation for 6 h, respectively. As shown in Figure 3a, green ICG fluorescence was found in the cytoplasm, while red DOX fluorescence was found in the nucleus. In 4T1 cells, PNMAuDIs plus laser irradiation showed the strongest intracellular fluorescence of ICG and DOX, indicating that the higher affinity of interacting receptors improves the cellular uptake of PNMAuDIs ( image 3 b). To examine the photothermal efficiency of PNMAuDIs, temperature changes were recorded. Laser irradiation via a thermal imaging camera. When at 1W·cm -2 When exposed to laser light for 5 min, the temperature of saline, ICG, AuDIs and PNMAuDIs increased to 30.2, 50.3, 57.3 and 58.1 °C, respectively. In ICG solution, a lower temperature exists compared with AuDIs due to...

Embodiment 3

[0116] Example 3: The ability of PNMAuDIs to bind exosomes in vitro

[0117] Recent reports have shown that tumor-derived exosomes are critical to the invasion-metastasis cascade. Among them, exosomes enable uncontrolled disease progression, promote a niche for cancer growth and suppress immune cell function. To explore the binding ability of exosomes to PNMAuDIs, exosomes were stained with DiO, and platelet and neutrophil membranes were prelabeled with DiD. Confocal was used to explore the interaction between PNMAuDIs and exosomes. Such as Figure 4 In a, NMAuDIs, PMAuDIs, and PNMAuDIs were incubated with exosomes, among which all PNMAuDIs were the most co-localized. In addition, co-localization was observed and demonstrated by electron microscopy ( Figure 4 b). The increase in particle size and decrease in zeta potential also confirmed the co-localization of PNMAuDIs and exosomes, possibly due to the similarity of membrane proteins between tumor cells and tumor-secrete...

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Abstract

The invention relates to the technical field of medicines, and relates to adriamycin-indocyanine green bionic nanoparticles coated with platelet and neutrophil fusion membranes and an application of the adriamycin-indocyanine green bionic nanoparticles in preparation of medicines for treating tumor metastasis diseases. The bionic nanoparticle coated with the platelet and neutrophil hybrid membranecomprises adriamycin, indocyanine green, a nano carrier material, a platelet membrane and a neutrophil hybrid membrane, which is characterized by comprising the following components in percentage byweight: 8 to 10 percent of doxorubicin, 8 to 10 percent of indocyanine green, 30 to 40 percent of nano carrier material and the balance of platelet and neutrophile granulocyte hybrid membrane. The bionic nanoparticle has the capability of simultaneously capturing and removing circulating tumor cells and tumor-derived exosomes through a high-affinity membrane adhesion receptor, and effectively cutsoff the relationship between the exosomes and immune cells. The primary tumor can be completely ablated, and breast cancer metastasis can be efficiently inhibited in xenograft and in-situ breast tumor models.

Description

technical field [0001] The present invention relates to the field of pharmaceutical technology, and relates to a biomimetic nanoparticle co-carrying doxorubicin and indocyanine green and its application, in particular, to a method for thoroughly ablation of primary tumors, targeting circulating tumor cells and exocytosis The fusion membrane-coated doxorubicin-indocyanine green biomimetic nanoparticles of platelets and neutrophils inhibiting tumor metastasis and its use in the preparation of drugs for treating tumor metastases. Background technique [0002] Metastatic breast cancer (Stage IV) is a malignant tumor in which the disease has spread to distant sites. Metastasis is responsible for approximately 90% of breast cancer deaths, and despite significant advances in cancer treatments, they have not been effective in improving survival in metastatic breast cancer. The main reason for this is that current treatments cannot effectively eliminate free circulating tumor cells ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/50A61K31/704A61K41/00A61K47/69A61K47/46A61P35/04B82Y5/00
CPCA61K9/5068A61K31/704A61K41/0052A61K47/6949A61P35/04B82Y5/00A61K2300/00
Inventor 孙进何仲贵叶皓王开元
Owner SHENYANG PHARMA UNIVERSITY
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