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Photosensitizer targeting nanoparticles used for optical therapy as well as preparation method and applications of photosensitizer targeting nanoparticles

A technology targeting nanoparticles and photosensitizers, which is applied in the field of nanobiomedicine, can solve the problems of inability to specifically enter the lesion, lack of targeting, instability, etc., achieve uniform size, good targeting effect, reduce toxic effect

Active Publication Date: 2017-12-01
THE AFFILIATED HOSPITAL OF XUZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, indocyanine green is unstable in physiological media, and is easily eliminated by non-specific adsorption with proteins in the culture medium or blood (ChristianDA, Cai S, Bowen DM, et al. Polymersome carriers: from self-assembly to siRNA andprotein therapeutics.Eur J Pharm Biopharm.2009,71(3):463-474.), and it also has no targeting, so it cannot specifically enter the lesion, these shortcomings limit its application

Method used

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  • Photosensitizer targeting nanoparticles used for optical therapy as well as preparation method and applications of photosensitizer targeting nanoparticles
  • Photosensitizer targeting nanoparticles used for optical therapy as well as preparation method and applications of photosensitizer targeting nanoparticles
  • Photosensitizer targeting nanoparticles used for optical therapy as well as preparation method and applications of photosensitizer targeting nanoparticles

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Experimental program
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Embodiment 1

[0024] Embodiment 1: Synthesis and characterization of PAMAM-COOH

[0025] The positive charge of the amino group on the surface of PAMAM makes it cytotoxic to a certain extent. In order to make it have better biocompatibility, it can be modified on the surface. This study intends to use succinic anhydride to modify PAMAM, and change most of the amino groups on the surface of PAMAM to safer carboxyl groups, so as to obtain PC nanoparticles ( figure 1 A).

[0026] The synthesis method is as follows: put 1.5mL of PAMAM-G5.0 (290mg, 0.01mmol) in methanol solution into a single-necked flask, spin dry, and add 1mL of anhydrous DMSO to redissolve. Succinic anhydride (640 mg, 6.4 mmol) was dissolved in 1 mL of anhydrous DMSO, added dropwise into the reaction system, and stirred at room temperature for 24 h. After three days of dialysis using a dialysis bag with Mw=3500Da, it was freeze-dried to obtain the product PAMAM-COOH (PC). The infrared spectrum of the product was analyzed b...

Embodiment 2

[0028] Example 2: Synthesis and characterization of HA-PAMAM-COOH-TMZ, HA-PAMAM-COOH-ICG and HA-PAMAM-COOH-TMZ-ICG

[0029] 5 mg PC (prepared in Example 1) and 2 mg TMZ were co-dissolved in 0.5 mL deionized water to obtain liquid A, and 3 mg TMZ and 5 mg HA were co-dissolved in 2 mL deionized water to obtain liquid B. Liquid B is placed under the ultrasonic probe with a power of 180W, and liquid A is added dropwise to liquid B while ultrasonicating. After ultrasonication for 10 minutes, use a 30K ultrafiltration tube to ultrafilter the liquid obtained after ultrasonication at a speed of 6000rpm / min. After the concentrated solution was washed three times with deionized water, TMZ-loaded nanoparticles (HA-PAMAM-COOH-TMZ, HPCT) were obtained by freeze-drying.

[0030] 5 mg of PC (prepared in Example 1) and 0.15 mg of ICG were co-dissolved in 0.5 mL of deionized water to obtain liquid A, and 5 mg of HA was dissolved in 2 mL of deionized water to obtain liquid B. Liquid B is place...

Embodiment 3

[0033] Embodiment 3: TMZ content determination

[0034] In order to accurately determine the content of drug TMZ, we determined the degradation curve of TMZ. A certain amount of TMZ was dissolved in PBS with pH=7.4 to make a solution of 50 μg / mL, and placed on a shaker at 37° C. at a speed of 150 rpm / min. At regular time intervals, 200 μL of the liquid was taken out, and the ultraviolet absorption spectrum at 200-400 nm was measured.

[0035] Since TMZ is unstable in aqueous solution, it will gradually degrade into the compound MTIC (5-(3-methyltriazen-1-yl)imidazol-4-amide), so it is necessary to establish a method for the determination of TMZ and MTIC. The ultraviolet absorption method measurement result shows that the strongest absorption peak of TMZ is positioned at 328nm, and the strongest absorption wavelength of its degradation product MTIC is 266nm ( image 3A), while HPCT nanoparticles have no absorption at this wavelength and will not interfere with the determinati...

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Abstract

The invention discloses photosensitizer targeting nanoparticles for optical therapy as well as a preparation method and applications of the photosensitizer targeting nanoparticles. The general formula of the targeting nanoparticles is HA-PAMAM-COOH-ICG, wherein HA is hyaluronic acid, PAMAM is a dendritic polymer, COOH is carboxyl, and ICG is indocyanine green. The nanoparticles provided by the invention are good in stability, realize the advantage that the local concentration of the medicine is high through the targeting effect after being administrated, are basically free of toxic and side effects, can be used for carrying out fluorescence imaging research on the accumulation condition of the medicine in a tumor, and also can be used as a photosensitizer for exerting the curative effects of PTT / PDT.

Description

technical field [0001] The invention belongs to the technical field of nano-biomedicine, in particular, it relates to a photosensitizer-targeted nanoparticle for phototherapy and its preparation method and application, in particular to an indocyanine green with a dendritic polymer as a carrier Targeting nanoparticles and their preparation methods and applications. Background technique [0002] Melanoma is a skin tumor caused by excessive hyperplasia of abnormal melanocytes. It is highly malignant and has a poor prognosis. Its fatality rate accounts for about 80% of skin tumor deaths. In recent years, the incidence rate has been increasing, with an annual growth rate of 3-5%, and has a younger trend (Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer JClin. 2016, 66(1): 7- 30.). Chemotherapy drugs commonly used in clinical treatment of melanoma include dacarbazine, temozolomide (TMZ), platinum, paclitaxel, and formustine, etc., but the curative effect is not ...

Claims

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Application Information

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IPC IPC(8): A61K49/00A61K41/00A61K9/51A61K47/36A61K47/34A61P35/00
CPCA61K9/5146A61K9/5161A61K41/0052A61K41/0057A61K49/0034A61K49/0054A61K49/0093
Inventor 蒋冠唐建琴侯晓阳李荣花庞雁宇刘彦群辛勇
Owner THE AFFILIATED HOSPITAL OF XUZHOU MEDICAL UNIV
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