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Carrier-free self-assembled nano particle as well as preparation method and application thereof

A nanoparticle and self-assembly technology, applied in the field of biomedicine, can solve the problems of poor biocompatibility and stability, complicated and tedious preparation process, and inability to take effect on remote tumors, and achieves high stability of the drug, efficient enrichment, good The effect of in situ tumor clearance

Active Publication Date: 2021-11-19
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] In order to solve the shortcomings of the existing nano-carrier system, such as low drug loading and pre-alkalinization treatment, resulting in complex and cumbersome preparation process, poor biocompatibility and stability, and the introduction of nano-carriers to bring immunogenicity and toxicity, For the problem of being unable to take effect on distant tumors, the present invention proposes a carrier-free self-assembled nanoparticle and its preparation method and application. Two drug molecules, a photosensitizer and an imidazoquinoline Toll-like receptor agonist, are used as active ingredients The construction of carrier-free self-assembled nanoparticles can be prepared into nanoparticles with good stability without the use of alkaline reagents, reducing the complexity of preparation and improving production efficiency
At the same time, the nanoparticles solved the problems of poor water solubility and low bioavailability of two hydrophobic drugs. Compared with other control groups, chlorin and Toll-like receptor agonist nanoparticles (Ce6-IMDQ NPs) showed higher Good in situ tumor clearance and significant inhibition of distant tumor growth by combined photodynamic-immune therapy

Method used

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  • Carrier-free self-assembled nano particle as well as preparation method and application thereof

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preparation example Construction

[0038] The second aspect of the present invention provides a method for preparing carrier-free self-assembled nanoparticles, comprising: dissolving a photosensitizer and an imidazoquinoline agonist in an organic solvent respectively, adding water after mixing, continuing the reaction, and centrifuging.

[0039] The photosensitizer and the imidazoquinoline agonist are mixed in an organic solvent, and then the mixed solution is added into water to assemble.

[0040] In some existing carrier-free nanoparticles, chlorin needs to be alkalized first, and then self-assembled with chemotherapy drugs. The preparation method is complicated, and it cannot act on distant tumors.

[0041] In some embodiments of the present invention, photosensitizers and imidazoquinoline agonists are dissolved in organic solvents, and the existence of non-covalent bond electrostatic interaction and hydrophobic interaction / π-π stacking between molecules inside the particles maintains a good relationship betw...

Embodiment 1

[0057] Embodiment 1: the preparation of nanoparticle

[0058] The preparation method of chlorin and Toll-like receptor agonist nanoparticles (Ce6-IMDQ NPs) is as follows:

[0059] (1) Accurately weigh a certain amount of Ce6 with an analytical balance, and disperse it in dimethyl sulfoxide (DMSO) to make a 5 mg / mL solution. A certain amount of IMDQ was weighed and dispersed in dimethyl sulfoxide (DMSO) to make a 2 mg / mL solution. The two were mixed in equal volumes, and the mixed solution was added dropwise to 1 mL of water under rapid stirring, and the stirring was continued for 5 minutes.

[0060] (2) After the reaction, the mixed solution was centrifuged (10,000 g, 5 min), and the operation was repeated 3 times. After each centrifugation, 1 mL of ultrapure water was added to remove unreacted substances, and the nanoparticles were obtained after sterilization.

Embodiment 2

[0061] Embodiment 2: Characterization of the physical and chemical properties of nanoparticles

[0062] The UV spectrum was measured with a UV-Vis spectrophotometer (Shimadzu, UV-2600). The morphology of nanoparticles was characterized by transmission electron microscope (TEM, JEOL JEM-1400) and scanning electron microscope (SEM, Carl Zeiss G300). The result is as Figure 1-3 As shown, the prepared nanoparticles are regular in shape and uniform in size, and the particle size is about 180nm. The ultraviolet spectrum confirms that the nanoparticles are assembled by two small molecule drugs.

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Abstract

The invention relates to the technical field of biological medicine, in particular to carrier-free self-assembled nanoparticles as well as a preparation method and an application thereof. The carrier-free self-assembled nano particle is composed of two drug molecules, namely, the photosensitizer and the imidazo quinoline Toll-like receptor stimulant, the preparation method is simple, and the problems that the two hydrophobic drug molecules are poor in water solubility and low in bioavailability are solved at the same time. Compared with other control groups, the photosensitizer chlorin and the Toll-like receptor stimulant nanoparticles (Ce6-IMDQ NPs) show a better in-situ tumor removal effect, and the growth of far-end tumors can be remarkably inhibited through photodynamic-immune combined treatment.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a carrier-free self-assembled nanoparticle and its preparation method and application. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] Major diseases such as cancer seriously threaten human health, causing significant death and economic losses. At present, the commonly used cancer treatment methods are mainly surgery, chemotherapy, radiotherapy, photothermal therapy, photodynamic therapy and immunotherapy. Immunotherapy is a method to achieve therapeutic purposes by triggering and training the host immune system to attack tumor cells, and has attracted widespread attentio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K41/00A61K31/4745A61K9/14A61P35/00B82Y5/00B82Y40/00
CPCA61K45/06A61K41/0071A61K31/4745A61K9/14A61P35/00B82Y5/00B82Y40/00A61K2300/00
Inventor 崔基炜张贵强于群郝京诚
Owner SHANDONG UNIV
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