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A nanomicelle activated by short-term near-infrared light for rapid drug release

A near-infrared light and nanomicelle technology, which is applied in the application of rapid drug release and the preparation of nanomicelles, can solve the problems of slow drug release rate, thermal damage to cells and tissues, unfavorable clinical application, etc., and achieves short illumination time. , good stability and high drug release efficiency

Active Publication Date: 2022-03-18
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, for Tm 3+ Doped UCNPs, electrons reach high-energy excited states 1 D. 2 The transition of is often difficult to occur, so from 1 D. 2 → 3 h 6 The quantum yield of ultraviolet light emission generated by the transition is very low (usually less than 1%), resulting in a slow release rate of the drug, often requiring several hours of light stimulation to achieve the drug concentration required for treatment, which may cause thermal damage to the tissue. damage, which is not conducive to the further development of clinical application

Method used

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  • A nanomicelle activated by short-term near-infrared light for rapid drug release
  • A nanomicelle activated by short-term near-infrared light for rapid drug release
  • A nanomicelle activated by short-term near-infrared light for rapid drug release

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Example 1: Combining image 3 , Synthesis of 800CW modified upconversion nanoparticles UCNPs-CW.

[0016] 200mg NaYF 4 :Gd@NaYF 4 : Er, Yb@NaYF 4 : Yb, Nd(UCNPs) dispersed in 10mL CHCl 3 Add 50mg of alendronic acid (ADA), 6mL of pure water and 4mL of ethanol, and adjust the pH value of the mixture to about 2 with 1M hydrochloric acid. After stirring at room temperature for 30 minutes, the upper aqueous phase was collected, centrifuged to obtain UCNPs-ADA, washed several times with pure water, and dispersed in 10 mL of pure water. Then mix 5mL 1mg / mL UCNPs-ADA with 3μL 0.5mM Mixed and stirred overnight at room temperature, centrifuged and washed several times with THF, dispersed in 5 mL THF (Solution A). After 2 μL caprylic acid was mixed with 100 μL LEDC (0.1M), 100 μL NHS (0.1M) and 300 μL THF and stirred at room temperature for 2 hours, it was added to 5 mL solution A and stirred at room temperature for 8 h. The obtained hydrophobic UCNPs-CW were centrifuged, ...

Embodiment 2

[0017] Example 2: Combining Figure 4 , Synthesis of amphiphilic polymer long-chain P-DASA.

[0018] Add 15.48mmol n-dodecylamine and 15.48mmol n-dodecyl isocyanate to 130mL CH 2 Cl 2 , stirred at room temperature for 1 h under nitrogen protection, then added 15.48 mmol of malonyl chloride and heated to reflux for 1 h. After cooling to room temperature, add 60mL of 1M hydrochloric acid and mix well, and the crude product is washed with CH 2 Cl 2 extraction. The organic phase was washed with water and MgSO 4 Drying and purification by column chromatography (hexane: ethyl acetate = 9:1 to 4:1) gave product 1.

[0019] 13.6 mmol of 2-furan aldehyde was added to 27 mL of an aqueous solution containing 13.6 mmol of compound 1, and stirred at room temperature for 10 h. use CH 2 Cl 2 Extraction product (compound 2), organic phase is passed through MgSO 4 Dry, filter and dry in vacuo.

[0020] 2.32 mmol of 6-azido-N-ethylhexan-1-amine was added to 5 mL of a THF solution con...

Embodiment 3

[0022] Example 3: Binding figure 1 , Synthesis of upconversion nanomicelle UCNPs-CW / DOX@P-DASA.

[0023] 2 mg DASA-PEG was dispersed in 2.7 mL THF, mixed with 1 mg UCNPs-CW and 100 μL 0.4 mg / mL DOX and sonicated for 20 min. The mixture was then added dropwise to 60 mL of water and stirred at 37 °C for 8 h. The generated upconversion nanomicelle UCNPs-CW / DOX@P-DASA was collected by centrifugation (4000r, 5 minutes) and dispersed in 2 mL of water.

[0024] Nanomicelle DOX@P-DASA without UCNPs-CW was synthesized using a similar method, and UCNPs-CW was not added during the synthesis.

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Abstract

The invention relates to a preparation method of nano micelles responding to short-time near-infrared light and its application in rapid drug release. This method utilizes hydrophilic polyethylene glycol and hydrophobic donor-acceptor Stenhouse adduct (DASA) to form an amphiphilic polymer chain P-DASA, and prepares an Er-coated 3+ Nanomicelles doped with upconverting nanoparticles (UCNPs) and the anticancer drug doxorubicin. Under near-infrared light, the green light (541nm) emitted by UCNPs promotes the transformation of hydrophobic DASA into hydrophilic, resulting in the disintegration of micelles and the release of doxorubicin. Only 5 minutes of light (808nm, 2W / cm 2 ) after stimulation, the release rate of the drug reaches more than 80% within 30 minutes. The present invention provides a short-time light-activated near-infrared light-controlled drug release system, which is of great significance for the clinical application and development of up-conversion nanomaterials in the fields of drug delivery and precise diagnosis and treatment of cancer.

Description

1. Technical field [0001] The invention relates to the technical field of application of nano-micelle drug loading system, in particular to a preparation method of nano-micelle responding to short-time near-infrared light and its application in rapid drug release. 2. Background technology [0002] Polymer nanomaterials with micellar structure have been widely used in biomedical research and disease treatment. They are usually formed by the self-assembly of long chains of amphiphilic polymers in aqueous solution. Inside, the hydrophilic part is exposed to the outside, forming nanoparticles with a hydrophobic inner core and a hydrophilic outer layer that are stably dispersed in aqueous solution. Its hydrophilic shell provides good water solubility and biocompatibility, while the hydrophobic core has good drug loading capacity, so it becomes an ideal drug delivery vehicle. [0003] By modifying stimuli-responsive groups in the long chains of polymers as the structural units of...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/107A61K41/00A61K47/34A61K31/704A61P35/00
CPCA61K9/1075A61K9/0009A61K41/0042A61K47/34A61K31/704A61P35/00
Inventor 鞠熀先刘颖张玥
Owner NANJING UNIV