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Ultra-small protein composite nanoparticles with near-infrared photothermal effect and multimodal imaging functions, its preparation method and application

A multi-modal imaging, near-infrared light technology, applied in medical preparations containing active ingredients, echo/ultrasonic imaging agents, preparations for in vivo experiments, etc., can solve the problem of insufficient diagnosis or treatment performance, poor soft tissue contrast , angiography failure and other problems, to achieve the effect of low cost, small dose, strong X-ray attenuation ability

Active Publication Date: 2020-10-02
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, pharmacokinetic limitations such as short circulating half-life and nonspecific distribution of clinically used CT contrast agents (chelated iopromide) may lead to failure of tumor-targeted imaging and angiography
Moreover, CT imaging still has some inherent limitations, especially the disadvantages of poor soft tissue contrast and radiation, which are the shortcomings of CT in clinical diagnosis.
[0005] Since most of the currently reported protein nanoreactors are single-component products obtained from a single reaction, the diagnostic or therapeutic performance is not perfect, and further modification is required to obtain more imaging and therapeutic functions. , which simultaneously initiates and controls two or more reactions reported by

Method used

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  • Ultra-small protein composite nanoparticles with near-infrared photothermal effect and multimodal imaging functions, its preparation method and application
  • Ultra-small protein composite nanoparticles with near-infrared photothermal effect and multimodal imaging functions, its preparation method and application
  • Ultra-small protein composite nanoparticles with near-infrared photothermal effect and multimodal imaging functions, its preparation method and application

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Experimental program
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Effect test

Embodiment 1

[0046] 1. Preparation of albumin composite nanoparticles:

[0047] First prepare 50 mg·mL -1 Bovine serum albumin solution 10 mL, then add 2 mL Bi(NO 3 ) 3 ·5H 2 O (20 mmol·L -1 ), 2 mL GdCl 3 ·6H 2 O (20 mmol·L -1 ). The reaction system was then adjusted to pH 12 with 2 M NaOH to obtain a mixture solution. Finally, the mixture solution was placed in a 37 °C water bath and heated for 12 h. After the reaction time is up, place the reaction solution in a dialysis bag with a molecular weight cut-off of 8000-14000 KD, dialyze with pure water for 24 h to remove small molecular impurities in the reaction, and then filter the reaction solution with an ultrafiltration centrifuge tube at 3000 r min -1 Centrifuge for 15 min, wash with water for 10 times, and then centrifuge and concentrate to obtain the purified product, which is protein composite nanoparticles with near-infrared photothermal effect and multimodal imaging function, referred to as nanoparticles or DCNPs.

[00...

Embodiment 2

[0091] When preparing albumin composite nanoparticles in Example 1, adjust the bovine serum albumin concentration to 10, 25, 75, 100 mg·mL -1 , the other steps are the same as in Example 1, and albumin composite nanoparticles with better stability can be obtained. The particle size of the albumin composite nanoparticles prepared by this method is measured at 25°C with a laser particle size analyzer. 0.5 mmol·L -1 aqueous solution under laser light (785 nm, 1.5 W cm -2 ) after 300 s of irradiation, the temperature can be increased by 30°C, 31°C, 31°C, and 31°C, respectively; the photothermal conversion efficiencies are 41.98%, 42.03%, 41.87%, and 40.16%, respectively; all of them can be used for multi-modal imaging.

Embodiment 3

[0093] Adjust the reaction system to pH 8, 10, and 13 during the preparation of albumin composite nanoparticles in Example 1, and the other steps are the same as in Example 1; as the pH of the aqueous phase in the reaction system increases, the albumin composite nanoparticles can be adjusted. The intensity of absorption in the near-infrared region of 800-1200 nm can produce albumin composite nanoparticles with better stability. The particle size of albumin composite nanoparticles prepared by this method is measured at 25 ℃ with a laser particle size analyzer. About, bismuth element content is 0.5 mmol L -1 aqueous solution under laser light (785 nm, 1.5 W cm -2 ) after irradiating for 300 s, the temperature can be increased by 30 ℃, 30 ℃ and 31 ℃ respectively; the photothermal conversion efficiency is 42.18%, 42.33% and 42.37% respectively; all of them can be used for multi-modal imaging.

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Abstract

The invention discloses a bismuth sulfide / gadolinium oxide-entrapping ultrafine protein composite nanoparticle with a near-infrared photothermal effect and a multi-mode imaging function and a preparation method and application thereof. By formulation screening and process optimization, the bismuth sulfide / gadolinium oxide albumin ultrafine composite nanoparticle with the near-infrared photothermaleffect and the multi-mode imaging function is prepared in one step. The composite nanoparticle has good physicochemical stability, photostability, biocompatibility and tumor-targeting property, can remarkably enhance near-infrared fluorescence, photoacoustic, magnetic resonance, CT (computed tomography) and thermal signals at a tumor site, and realizes multi-mode-complemented tumor diagnosis, andmoreover, the composite nanoparticle can eliminate tumors under the excitation of near-infrared light; in particular, because the grain size of the nanoparticle is less than 5.5nm, the nanoparticle can be eliminated by the kidneys, and toxic and side effects are minor; a tumor can be diagnosed and treated at the same time, and the composite nanoparticle has a great potential in realizing accuratetumor diagnosis and treatment integration.

Description

technical field [0001] The invention relates to an ultra-small protein composite nanoparticle with near-infrared photothermal effect and multi-modal imaging function simultaneously carrying two components of bismuth sulfide and gadolinium oxide, as well as its preparation method and application. Background technique [0002] In recent years, with the deterioration of the global environment and the increase in the pressure of life, the incidence of many cancers has shown a continuous upward trend. Early detection and early treatment have become the consensus of all parties. Therefore, breakthroughs and innovations in cancer diagnosis and treatment methods focus on the development of efficient, safe and accurate tumor diagnosis and treatment methods for solid tumor types. Numerous studies have shown that when the surrounding temperature of tumor cells is higher than 43 ℃, cell apoptosis will be induced. Therefore, photothermal therapy has received more and more attention in re...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/00A61K49/22A61K49/04A61K49/18A61K49/14A61K41/00A61P35/00
Inventor 陈华兵杨红柯亨特吕小燕邓益斌王雪杨涛李明徐涛
Owner SUZHOU UNIV
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