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Ultrasmall molecule H-dot nano drug delivery system-based lung cancer diagnosis and treatment integrated targeting nano drug and preparation method thereof

A nano-drug loading and nano-drug technology, which is applied in the direction of nano-drugs, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., to avoid non-specific absorption, accurately obtain materials, and reduce the risk of recurrence and metastasis Effect

Pending Publication Date: 2022-04-15
THE SECOND AFFILIATED HOSPITAL OF XIAN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the progress of engineered nanomedicines remains extremely challenging since precise nanomedicine engineering needs to consider factors such as drug shape, hydrodynamic diameter, surface charge, solubility, stability, flexibility, composition, and formulation.

Method used

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  • Ultrasmall molecule H-dot nano drug delivery system-based lung cancer diagnosis and treatment integrated targeting nano drug and preparation method thereof
  • Ultrasmall molecule H-dot nano drug delivery system-based lung cancer diagnosis and treatment integrated targeting nano drug and preparation method thereof
  • Ultrasmall molecule H-dot nano drug delivery system-based lung cancer diagnosis and treatment integrated targeting nano drug and preparation method thereof

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Embodiment 1

[0047] The preparation of embodiment 1H-dot

[0048] β-CD into Ald-CD: 15g of β-CD (13.22mmol) was dissolved in 100mL of anhydrous DMSO, and 6.73g of DMP (15.86mmol) was added to the solution, stirred at room temperature for 2h; after 2h , the above reaction solution was poured into a mixture of ethyl acetate / acetone (20% v / v) at 4°C for precipitation, and stored at 4°C overnight. The next day, the precipitate was recovered by vacuum filtration and dissolved in DMSO; then this solution was poured into 750 mL of cold ethyl acetate / acetone (20% v / v), centrifuged at 3000 rpm for 15 min, and the supernatant was discarded; The precipitate was redissolved in deionized water, and poured into ethyl acetate / acetone again to precipitate, and the above operation was repeated twice; after the last precipitation, the precipitate was dissolved in 75 mL of deionized water and stirred for 1 h; then freeze-dried to remove the compound Acetone and DMSO, after freeze-drying, can recover 16g of ...

Embodiment 2

[0053] The preparation of embodiment 2Gef / H-dot

[0054] The three-dimensional structure of β-CD was selected as the pair acceptor (Protein Data Bank ID code: 1BFN). Ligands were energy minimized using the CHARMm force field, and the model with the lowest binding energy was selected using the CDOCKER protocol in Discovery Studio 3.0 software.

[0055] To prepare the Gef / H-dot800 complex, dissolve Gef salt in 2mM deionized water, dissolve H-dot800 powder in 1mM deionized water, adjust the pH of the above solution to 5.33 with about 0.3M hydrochloric acid solution; Mix at a volume ratio of 1:1 and vortex at room temperature for 60 min; then, centrifuge the solution at 14,000 rcf for 10 min to precipitate impurities, collect and freeze-dry the supernatant to obtain the Gef / H-dot product, and use UV spectrophotometry Determine the molar ratio of Gef to H-dot. The target drug of the present invention and H-dot molar ratio see figure 2 , where a is the UV absorption spectrum of ...

Embodiment 3

[0057] The characterization of embodiment 3H-dot

[0058] Ninhydrin test to estimate the number of amine groups: The ninhydrin reagent was prepared by dissolving 0.8 g of ninhydrin in 10 mL of ethanol (8 wt%). Transfer 1 mL of the reaction solution into three separate 10 mL scintillation vials, add 20 μL of the reaction mixture before adding succinic anhydride (SA, succinicanhydride) to the first vial as a reference, and add 20 μL to the second vial 30 min after adding SA Add 20 μL of PBS to the third vial as a negative control; vortex the vial, place in a boiling water bath for 5 min and then place in an ice bath for 3 min to cool; use a UV / Vis / NIR spectrometer at 570 nm Absorbance of each diluted solution, using negative control as blank; after 30min, the absorbance of the reaction mixture at 570nm is about half of that of the reference mixture, indicating that about half of the free amines have been succinylated, indicating that H-dot has amphoteric ions characteristic.

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Abstract

The invention discloses a lung cancer diagnosis and treatment integrated targeted nano-drug (Gef / H-dot) based on an ultra-small molecule H-dot nano-drug delivery system and a preparation method thereof, and belongs to the technical field of targeted nano-drugs, the preparation method comprises the following steps: converting beta-CD into Ald-CD, combining the Ald-CD with EPL to form CDPL, combining the CDPL with a near infrared (NIR) fluorophore, and carrying out succinylation to obtain the targeted nano-drug (Gef / H-dot). The preparation method comprises the following steps: obtaining NIR fluorophor-CDPL + / -, naming the NIR fluorophor-CDPL + / -as H-dot, and compounding H-dot with a Gef targeted drug to obtain Gef / H-dot; the nano-drug is an ideal multifunctional nano-drug, has infinite potential in the aspects of staged detection, surgical intervention and pathological assistance guided by a real-time NIR fluorescence image, and also can directionally convey an anti-tumor drug (Gef), so that efficient targeted therapy is realized, and adverse reactions related to treatment are reduced.

Description

technical field [0001] The invention relates to the technical field of targeted nano-medicines, in particular to a targeted nano-medicine based on an ultra-small molecule H-dot nano-drug loading system for lung cancer diagnosis and treatment integration and a preparation method thereof. Background technique [0002] To improve the survival rate of lung cancer patients, a novel perioperative treatment strategy has been developed using multifunctional nanoparticle therapy before and after surgical resection (i.e., neoadjuvant / adjuvant therapy). This perioperative approach helps control micrometastases and reduces the risk and difficulty of surgical resection. Based on this, multifunctional nanomedicine has attracted much attention as a new generation of targeted therapy. [0003] Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used clinically as a standard treatment for EGFR-mutant NSCLC, and their development has led to considerable p...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K31/5377A61K47/64A61K49/00A61P11/00A61P35/00B82Y5/00
Inventor 尹晓然崔學秀姜鎬萬崔亚男程义凡
Owner THE SECOND AFFILIATED HOSPITAL OF XIAN JIAOTONG UNIV
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