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Preparation method of rare earth upconversion nano-drug carrier integrating fluorescence imaging and drug loading

A nano-drug carrier and rare earth up-conversion technology, which is applied in the field of nano-biomedicine, can solve the problems of low up-conversion luminous efficiency, cumbersome operation process, and poor drug immobilization, so as to reduce toxic and side effects, simple synthesis process, and good stability Effect

Inactive Publication Date: 2020-05-19
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Usually, the mesoporous structure on the surface has poor immobilization of drugs, and the drug is easy to leak from the pores, so it is necessary to modify the surface with a polymer protective layer (Lai, J.P.; Shah, B.P.; Zhang, Y.X.; Yang, L.T.; Lee, K.B.Real-time monitoring of ATP-responsive drug release using mesoporous-silica-coated multicolorupconversion nanoparticles.ACS Nano 2015,9,5234-5245.)
[0005] However, the above drug loading methods all require multi-step reactions and strict condition control, and the operation process is relatively cumbersome and time-consuming.
In addition, multiple treatments of upconversion nanoparticles increase the probability of quenching, leading to a decrease in the efficiency of upconversion luminescence.

Method used

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  • Preparation method of rare earth upconversion nano-drug carrier integrating fluorescence imaging and drug loading
  • Preparation method of rare earth upconversion nano-drug carrier integrating fluorescence imaging and drug loading
  • Preparation method of rare earth upconversion nano-drug carrier integrating fluorescence imaging and drug loading

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Synthesis of Example 1 Rare Earth Up-conversion Nanoparticles (UCNPs)

[0040] Accurately weigh yttrium chloride hexahydrate (YCl 3 ·6H 2 O) (0.2366g, 0.78mmol), ytterbium chloride hexahydrate (YbCl 3 ·6H 2 O) (0.0775g, 0.20mmol) and anhydrous erbium chloride (ErCl 3 ) (0.0055g, 0.02mmol) was added to a 100mL round-bottomed flask, then 6mL OA and 15mL 1-ODE were added, and the mixture was fully mixed and stirred. N 2 Warm up to 100°C under protection to remove O 2 and H 2 O, continue to heat up to 160 ° C for 40 min until the reactants are completely dissolved, and a light yellow transparent clear solution is obtained, which is cooled to room temperature. Also called NH 4 F 0.1482g (4mmol) and NaOH 0.1g (2.5mmol) were dissolved in 10mL of methanol, ultrasonically dispersed, and added dropwise to the previously cooled solution under vigorous stirring. Raise the temperature to 50°C, stir for 1h, then raise the temperature to 100°C, remove methanol and water. Aft...

Embodiment 2

[0042] Example 2 Preparation of rare earth up-conversion nano drug carrier by nanoprecipitation method

[0043] Upconverting nanoparticles (OA-UCNPs), distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG 2000 ), linolenic acid-modified SN38 prodrug 1 were ultrasonically dispersed in DMSO solution at concentrations of 12 mg / mL, 100 mg / mL, and 20 mg / mL, respectively. The three dispersions were mixed thoroughly, shaken slowly at room temperature for 4 hours, then added dropwise to ultrapure water under ultrasound, and continued to shake for 30 minutes. Centrifuge (15000g, 10min), discard the supernatant. The pellet was washed and centrifuged twice, then freeze-dried overnight. As a control, OA-UCNPs, DSPE-PEG 2000 , The DMSO solution of simple SN38 molecules was mixed and oscillated, and added dropwise into ultrapure water under ultrasonication. Rare earth upconversion nanocarriers of linolenic acid-modified cabazitaxel prodrug 2 were prepared by the same met...

Embodiment 3 Embodiment 2

[0046] Example 3 Determination of Rare Earth Up-conversion Nano Drug Carrier Drug Encapsulation Efficiency in Example 2

[0047] Immobilization of OA-UCNPs and DSPE-PEG 2000 The amount of prodrug 1 (mass ratio 1:2), different masses of prodrug 1 were added, and after full loading, the amount of drug 1 loaded on UCNPs was measured by UV-visible absorption spectrum (absorption peak at 367nm), and the drug loading rate was calculated. The drug loading of prodrug 2 was determined in a similar manner. Because the molar absorptivity of cabazitaxel is small, the absorption peak of UCNPs affects its determination. Therefore, the centrifuged supernatant and washing liquid were collected, and the unencapsulated 2 was measured to indirectly determine the drug entrapment. The characteristic ultraviolet absorption peak is 274nm, Simultaneously subtract DSPE-PEG at the same wavelength 2000 Absorption. Measured in parallel three times.

[0048] figure 2 is the measurement result of the...

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Abstract

The invention discloses a preparation method of a rare earth up-conversion nano-drug carrier integrated with fluorescence imaging and medicine carrying, wherein the preparation method includes steps of (1), using rare-earth chloride as a raw material, oleic acid as ligand, oleic acid / 1- octadecene as the mixed solution; applying a high-temperature solvent hot method to compound rare earth up-conversion nano particle (OA-UCNPs) coated by oleic acid; (2), dispersing the up-conversion nano particle, DSPE-PEG2000, antitumor drug in the same medium; applying an in-sit mixing method to mix the three parts fully, and happening hydrophobic interaction; (3) dropwise adding the mixture in the water solution through the nano precipitation method; compounding the drug-carrying nano particle in the process of dispersing and entering a water phase; (4), separating and purifying the drug-carrying nano particle, and drying the particle for future use.

Description

technical field [0001] The invention relates to a preparation method of a nano-medicine carrier, in particular to a simple preparation method of a rare-earth up-conversion nano-drug carrier capable of performing fluorescence imaging and encapsulating anti-tumor drugs at the same time, and belongs to the field of nano-biomedicine. Background technique [0002] Malignant tumor is one of the main diseases affecting human health. Currently, chemotherapy, surgery, and radiotherapy are the three major means of treating cancer. Chemotherapy specifically refers to the treatment of malignant tumors with chemical drugs, which are quickly distributed throughout the body after entering the human body. It is a systemic treatment. Because traditional chemotherapy drugs do not have obvious targeting, while killing tumor cells, they will also damage normal cells, tissues, and organs of the human body, resulting in obvious toxic and side effects, and reducing human immunity. At the same tim...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/00A61K9/51A61K47/34A61K47/02A61K47/54A61K31/4745A61K31/337A61P35/00
CPCA61K9/5115A61K9/5146A61K31/337A61K31/4745A61K49/0067
Inventor 王杭祥袁莹莹王敏
Owner ZHEJIANG UNIV
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