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Rare earth up-conversion nano-drug carrier integrated with fluorescence imaging and medicine carrying and application thereof

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: 2017-06-09
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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  • Rare earth up-conversion nano-drug carrier integrated with fluorescence imaging and medicine carrying and application thereof
  • Rare earth up-conversion nano-drug carrier integrated with fluorescence imaging and medicine carrying and application thereof
  • Rare earth up-conversion nano-drug carrier integrated with fluorescence imaging and medicine carrying and application thereof

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 rare earth up-conversion nano-drug carrier integrated with fluorescence imaging and medicine carrying and an application thereof. The nano-drug carrier includes a rare earth up-conversion nano particle (UCNPs) with fluorescence imaging function, anti-tumor drug loaded on the surface of the up-conversion nano particle, and amphiphilic polymer molecule distearoyl Phosphoethanolamine-polyethylene glycol (DSPE-PEG) coated on the surface of the nano particle. The nano drug carrier is uniform in dimension, regular in form, and good in both water solubility and biocompatibility; the surface structure is good for gathering at the tumor organization through EPR effect, and realizing the passive target of the drug.

Description

technical field [0001] The invention relates to a nano-medicine carrier and its application, in particular to a rare-earth up-conversion nano-medicine carrier capable of performing fluorescence imaging and encapsulating anti-tumor drugs at the same time and its application, belonging 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 time, traditiona...

Claims

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Application Information

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IPC IPC(8): A61K49/00A61K9/50A61K47/10A61P35/00A61K31/4745A61K31/337
CPCA61K9/5031A61K9/5078A61K31/337A61K31/4745A61K49/0019A61K49/0052A61K49/0093
Inventor 王杭祥袁莹莹王敏
Owner ZHEJIANG UNIV
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