Dc biomimetic membrane nanoparticle loaded with nir-ii aie dye, preparation method therefor and use thereof

Patent metadata

Field	Value
Publication number	US-2024398999-A1
Application number	US-202318326899-A
Country	US
Kind code	A1
Filing date	May 31, 2023
Priority date	May 31, 2023
Publication date	Dec 5, 2024
Grant date	—

Abstract

The present invention belongs to the field of nanomedicine, and provides a DC biomimetic membrane nanoparticle loaded with an NIR-II AIE dye, a preparation method therefor and use thereof. The DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye comprises a DC membrane and an NIR-II AIE dye loaded therein, wherein the NIR-II AIE dye has photothermal characteristics. The DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye provided by the present invention not only solves the problem that the NIR-II AIE dye is poor in water solubility and limited in fluorescence imaging, but also increases the enrichment efficiency of the NIR-II AIE dye coated by the DC membrane at a tumor site and successfully activates the activity of T cells in vivo.

First claim

What is claimed is:

1 . A DC biomimetic membrane nanoparticle loaded with an NIR-II AIE dye comprising a DC membrane and an NIR-II AIE dye loaded thereon, wherein the NIR-II AIE dye has photothermal characteristics.

2 . The DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 1 , wherein the DC membrane and the NIR-II AIE dye loaded thereon are subjected to the following method to obtain the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye:
dispersing DC cell membranes in PBS solution, then injecting the solution of the DC cell membranes through a filter by using a syringe, repeatedly operating so as to enable the cell membranes to be adhered to a filter membrane, aspirating the NIR-II AIE dye by using the syringe, enabling the NIR-II AIE dye to pass through the filter membrane having the cell membranes adsorbed thereto, and performing extrusion and filtration until the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye is obtained.

3 . The DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 1 , wherein the NIR-II AIE dye is a BPBBT dot.

4 . The DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 3 , wherein the BPBBT dot is prepared by the following method:
dissolving DSPE-PEG-2000 and BPBBT in an organic solvent, dropwise adding the mixed solution into deionized water under an ultrasonic condition, continuously carrying out ultrasonic treatment until a uniform emulsion is formed, removing the organic solvent in the emulsion, and filtering the obtained emulsion by using a filter to obtain the BPBBT dot.

5 . A method for preparing a DC biomimetic membrane nanoparticle loaded with an NIR-II AIE dye comprising the following steps:
S1: preparing the NIR-II AIE dye; and S2: dispersing DC cell membranes in PBS solution, then injecting the obtained solution of the DC cell membranes through a filter by using a syringe to enable the cell membranes to be fully adhered to a filter membrane, aspirating the NIR-II AIE dye prepared in S1 by using the filter, enabling the NIR-II AIE dye to pass through the filter membrane having the cell membranes adsorbed thereto, and performing extrusion and filtration until the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye is obtained.

6 . The method for preparing the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 5 , wherein the NIR-II AIE dye in S1 is a BPBBT dot and is prepared by the following method:
dissolving DSPE-PEG-2000 and BPBBT in an organic solvent, dropwise adding the mixed solution into deionized water under an ultrasonic condition, continuously carrying out ultrasonic treatment until a uniform emulsion is formed, removing the organic solvent in the emulsion, and filtering the obtained emulsion multiple times by using a filter to obtain the BPBBT dot.

7 . The method for preparing the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 6 , wherein a mass ratio of DSPE-PEG-2000 to BPBBT in S1 is 5:1 to 5:5, preferably 5:1, 5:2, 5:3, 5:4, or 5:5.

8 . The method for preparing the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 6 , wherein concentrations of DSPE-PEG-2000 and BPBBT in S1 in the organic solvent are 5 mg/mL and 1-5 mg/mL, respectively.

9 . The method for preparing the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 6 , wherein the ultrasonic treatment in S1 is carried out at a power of 100 W and a frequency of 40 KHz.

10 . The method for preparing the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 5 , wherein the DC cell membrane in S2 is obtained by a method comprising: isolating immature DCs from mouse bone marrow; stimulating with 4T1 cells and Poly I: C to obtain mature DCs, and then extracting to obtain DC cell membranes.

11 . The method for preparing the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 5 , wherein the filter membrane for the filter in S2 is a 0.22 μm filter membrane.

12 . Use of the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 1 in the preparation of a reagent for in vivo imaging, a reagent for image-guided photothermal therapy and a reagent for drug delivery systems.

13 . The use of the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye in the preparation of the reagents for in vivo imaging, the reagents for image-guided photothermal therapy and the reagents for drug delivery systems according to claim 12 , wherein the in vivo imaging or imaging guidance is in vivo imaging or imaging guidance in blood vessels, bile ducts and gastrointestinal tract in vivo.

14 . Use of the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 1 in the preparation of a photothermal therapeutic drug or a photothermal therapeutic sensitizer for the treatment of a tumor.

15 . Use of the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 1 in the preparation of a drug or reagent inhibiting expression of HSP70 at tumor sites, increasing thermal sensitivity of tumor cells and activating activity of T cells in vivo.

16 . A method for inhibiting a tumor comprising administering to a subject the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 1 .

17 . The method for inhibiting the tumor according to claim 16 comprising performing low-temperature photothermal therapy.

18 . The method for inhibiting the tumor according to claim 16 , wherein the tumor comprises lung cancer, melanoma, breast cancer, prostate cancer, colon cancer, renal cell carcinoma, ovarian cancer, pancreatic cancer, hepatocellular carcinoma, and rhabdomyosarcoma.

19 . A method for detecting a tumor comprising administering to a subject the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 1 , and imaging the AIE dye therein.

20 . A photothermal therapeutic drug or reagent comprising the DC biomimetic membrane nanoparticle loaded with the NIR-II AIE dye according to claim 1 .

Assignees

• Shenzhen Inst Of Adv Tech Cas
• Univ Hong Kong Science & Tech

Inventors

• Cai Lintao
• Yang Xing
• Gong Ping
• Zhang Pengfei
• Tang Benzhong
• Kwok Tsz Kin
• Yang Ting
• Liu Qiqi
• Zhang Xiuwen
• Yu Xinghua
• Hai Luo

Classifications

• A61K41/0052

  Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61K49/0021

  the fluorescent group being a small organic molecule · CPC title

• A61K49/0093 Primary

  Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle · CPC title