CN116159136B - Application of chiral nanomaterial in preparation of medicine for inducing neuron cells to produce IGF-1 - Google Patents
Application of chiral nanomaterial in preparation of medicine for inducing neuron cells to produce IGF-1 Download PDFInfo
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- CN116159136B CN116159136B CN202211658630.9A CN202211658630A CN116159136B CN 116159136 B CN116159136 B CN 116159136B CN 202211658630 A CN202211658630 A CN 202211658630A CN 116159136 B CN116159136 B CN 116159136B
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Abstract
The invention discloses a chiral compoundThe invention provides an application of a nanomaterial in preparing a medicament for inducing neuron cells to produce IGF-1, and provides a method for inducing insulin-like growth factor 1 to produce by using chiral nanomaterial under the action of light, which utilizes chiral Ni (OH) 2 The nanoparticle can be specifically combined with neuron cell membrane protein NGL-1, and can generate mechanical force under the action of near infrared light to induce the expression of IGF-1. The chiral nanometer material can realize the regulation and control of IGF-1 at the cellular and living body level, and IGF-1 is critical to maintaining the normal physiological needs of organisms, especially to the healthy development of the brain and the regeneration of damaged neurons. Therefore, the invention has important significance in the treatment of nervous system diseases such as spinal cord injury and the like.
Description
Technical Field
The invention relates to an application of chiral nano material in preparing medicine for inducing neuron cells to produce IGF-1, belonging to the technical field of nano medicine.
Background
Insulin-like growth factor 1 (IGF-1) is an active substance in the body, is a multifunctional cell regulator similar to insulin, plays an important role in promoting cell differentiation, individual growth and development, and is especially important for development and maturation of the central nervous system. IGF-1 can promote cell survival by inhibiting apoptosis, preventing neuronal death in neurodegenerative diseases and inhibiting oxidative stress and DNA damage, and has obvious neuroprotective effect. According to research reports, IGF-1 can be expressed transiently in the development process of the projection neurons, so that the survival rate of the neurons is enhanced; whereas IGF-1 deficiency leads to defects in brain development and function. IGF-1 has the ability to support motor neuron and sensory neuron regeneration and thus has potential utility in the treatment of neurological disorders.
In recent years, with development and progress of nanotechnology, nanoparticles with various materials, morphologies and unique chiral optical activities are continuously appeared, and have been applied to the fields of optical devices, catalysis, biological detection and the like. The chiral inorganic nano material can accurately regulate biological behaviors at the biological molecular level and the cellular level, and has important significance and value for understanding the intrinsic law of life body activities and diagnosing and preventing serious diseases.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides an application of a chiral nanomaterial in preparing a medicament for inducing neuron cells to generate IGF-1 under the action of near infrared illumination. The invention uses Ni (OH) with different chiral configurations 2 Nanoparticle co-incubation with neuronal cells using Ni (OH) 2 The nanometer particle has high affinity with the neurite growth inducing factor G1 ligand (NGL-1) of the surface membrane protein of the neuron cell membrane, and generates mechanical force under the action of illumination to activate the neurite guiding channel, thereby inducing the generation of IGF-1.
A first object of the present invention is to provide the use of a chiral nanomaterial for the preparation of a medicament for inducing the production of IGF-1 by neuronal cells, said medicament comprisingThe chiral nanomaterial is Ni (OH) with light response performance 2 And (3) nanoparticles.
Further, the Ni (OH) 2 The nanometer particle is combined with the ligand of neurite growth inducing factor G1 of neuron cell surface membrane protein specifically, and IGF-1 is produced under the action of near infrared illumination.
In the invention, the chiral nanomaterial can pass through the blood brain barrier through blood circulation, and activate the expression of IGF-1 in brain tissues under the action of light.
Further, the wavelength of the near infrared light is 800-1100nm.
Further, the Ni (OH) 2 The nanoparticle is D-type, L-type or DL-type. Preferred D-type Ni (OH) 2 And (3) nanoparticles.
In the invention, the medicine can act on the body, is injected into the body according to the dosage of 1.5-3 mug/g by adopting an injection mode, is injected into the body every 3-5 days, is treated for 8-16 hours under the near infrared light of 800-1100nm every day after injection, and is continuously treated for 10-15 days.
In the present invention, the agent may also act in vitro to induce IGF-1 production by co-incubation with neuronal cells.
A second object of the present invention is to provide a method for inducing a neuronal cell to produce IGF-1 under the effect of light by using a chiral nanomaterial, comprising the steps of:
ni (OH) 2 The nanoparticle is incubated with the neuronal cells and induced with near infrared light.
Further, the induction treatment is to irradiate with near infrared light for 5-15min every 2-6h, and continuously act for 24-48h.
Further, the wavelength of the near infrared light is 800-1100nm.
Further, the illumination power of the near infrared light is 100-300mW.
Further, the Ni (OH) 2 The concentration of the nano particles is 0.05-0.2mg/mL.
The mechanism of the invention:
chiral Ni (OH) in the present invention 2 Nanoparticle application in near infrared illuminationIn the lower, IGF-1 production can be induced at both cellular and in vivo levels.
The chiral Ni (OH) 2 The nanoparticle can be combined with a high-expression membrane receptor NGL-1 on the surface of a neuron, and under the action of near infrared light, mechanical force is generated between the nanoparticle and cells, so that an axon guiding channel is activated, and the IGF-1 is induced.
Ni (OH) with different chiral configurations 2 The degree of affinity of the nanoparticles to NGL-1 is different, resulting in a different magnitude of mechanical forces. D-Ni (OH) 2 The nanoparticles have the highest affinity for NGL-1 and the highest mechanical force and hence IGF-1 production.
The beneficial effects of the invention are as follows:
the invention provides a method for inducing insulin-like growth factor 1 to generate by chiral nano material under the action of light, which uses chiral Ni (OH) 2 The nanoparticle can be specifically combined with neuron cell membrane protein NGL-1, and can generate mechanical force under the action of near infrared light to induce the expression of IGF-1.
The chiral nanometer material can realize the regulation and control of IGF-1 at the cellular and living body level, and IGF-1 is critical to maintaining the normal physiological needs of organisms, especially to the healthy development of the brain and the regeneration of damaged neurons. Therefore, the invention has important significance in the treatment of nervous system diseases such as spinal cord injury and the like.
Description of the drawings:
FIG. 1 shows the chiral Ni (OH) of example 1 of the present invention 2 Statistics of relative expression levels of IGF-1mRNA in nanoparticles and light-treated neuronal cells;
FIG. 2 shows the chiral Ni (OH) of example 1 of the present invention 2 IGF-1 western blot results in nanoparticle and light-treated neuronal cells;
FIG. 3 shows Ni (OH) of different chiral configurations in example 2 of the present invention 2 Affinity of nanoparticles to NGL-1;
FIG. 4 shows chiral Ni (OH) in example 3 of the present invention 2 The nanoparticles generate mechanical force in the interaction process of the nanoparticles and the neuron cells under the illumination effect;
FIG. 5 is a schematic representation of chiral Ni (OH) after silencing NGL-1 in example 4 of the present invention 2 The result of the nanoparticle inducing IGF-1 production under the action of light;
FIG. 6 is a chiral Ni (OH) in example 5 of the present invention 2 The nanoparticles induce IGF-1 production in mice under the action of light.
Detailed Description
The present invention will be further described with reference to specific examples, which are not intended to be limiting, so that those skilled in the art will better understand the present invention and practice it. It should be understood that the experimental methods in the following examples, in which specific conditions are not noted, are generally performed under conventional conditions or under conditions suggested by the manufacturer. The various reagents commonly used in the examples are all commercially available products.
Example 1: chiral Ni (OH) 2 The nanoparticle induces IGF-1 production in neuronal cells under illumination
Ni (OH) with different chiral configurations 2 Incubating the nanoparticle and neuron cells, irradiating with 980nm laser for 10min at intervals of 2 hr with irradiation power of 200mW for 24 hr, extracting RNA from the cells, and performing RT-PCR to obtain chiral Ni (OH) compared with control group 2 IGF-1mRNA levels were increased in nanoparticle and light-treated neuronal cells, and D-Ni (OH) 2 Nanoparticle and light-treated IGF-1mRNA levels were higher than L-Ni (OH) 2 Nanoparticles and DL-Ni (OH) 2 Nanoparticles (as shown in figure 1). In addition, ni (OH) is extracted 2 The increased IGF-1 expression was further confirmed by western blot experiments with the nanoparticles and proteins in the light-treated neuronal cells (as shown in fig. 2).
Example 2: chiral Ni (OH) 2 Nanoparticle and neuronal cell surface membrane protein NGL-1 specific binding
To explore the mechanism of IGF-1 production, we performed chiral Ni (OH) 2 The affinity between the nanoparticle and the membrane protein NGL-1 highly expressed on the surface of the neuronal cell was tested. As shown in FIG. 3, the results were tested by isothermal titration calorimetryD-Ni (OH) was found 2 The affinity constant between the nanoparticle and NGL-1 is higher than that of L-Ni (OH) 2 Nanoparticles and DL-Ni (OH) 2 And (3) nanoparticles.
Example 3: chiral Ni (OH) 2 The nanoparticles generate mechanical force in the interaction process of the nanoparticles and the neuron cells under the illumination
Ni (OH) with different chiral configurations 2 The nanoparticle and the neuron cells are incubated together, and Ni (OH) is detected under the illumination effect 2 The interaction force between the nanoparticle and the neuron cell is shown in the experimental result as figure 4, which shows that the chiral Ni (OH) is improved by illumination 2 Binding force of nanoparticles to neuronal cell surface, and D-Ni (OH) 2 The binding force of the nano particles with the cell surface is the largest under the illumination effect.
Example 4: chiral Ni (OH) 2 Nanoparticle and light induced IGF-1 production is mediated by NGL-1
Based on the above analysis, the mechanism of IGF-1 production is chiral Ni (OH) 2 The nanoparticle is highly combined with neuron cell surface membrane protein NGL-1, and under the action of illumination, mechanical force is generated, so that the expression of IGF-1 is activated. Meanwhile, due to D-Ni (OH) 2 The affinity of the nano particles with NGL-1 is higher than that of L-Ni (OH) 2 Nanoparticles and DL-Ni (OH) 2 Nanoparticles, therefore, lead to more IGF-1 production. We used siRNA to silence neuronal cell NGL-1 expression, found chiral Ni (OH) 2 The inability of the nanoparticle to induce IGF-1 expression under light (as shown in FIG. 5) suggests that IGF-1 production is mediated by NGL-1.
Example 5: chiral Ni (OH) 2 The nanoparticles induce the production of IGF-1 at living body level under the action of light
Chiral Ni (OH) 2 Nanoparticles were injected into mice by tail vein, once every 5 days (dose 40 μg/dose), and irradiated for 12h (power 400 mW) per day, which was continued for 2 months, and the cerebrospinal fluid of the mice was withdrawn and found to increase in IGF-1 content (as shown in FIG. 6). This result illustrates chiral Ni (OH) 2 Nanoparticles that induce IGF-1 production under light irradiation can also be applied at the in vivo level.
The above-described embodiments are merely preferred embodiments for fully explaining the present invention, and the scope of the present invention is not limited thereto. Equivalent substitutions and modifications will occur to those skilled in the art based on the present invention, and are intended to be within the scope of the present invention. The protection scope of the invention is subject to the claims.
Claims (6)
1. A method for inducing neuron cells to produce IGF-1 by chiral nanomaterial under the action of light, comprising the following steps:
ni (OH) 2 The nanoparticle and the neuron cells are incubated in vitro, and induction treatment is carried out by adopting near infrared light; the induction treatment is to irradiate with near infrared light every 2-6h for 5-15min, and continuously act for 24-48h.
2. The method of claim 1, wherein the near infrared light has a wavelength of 800-1100nm.
3. The method according to claim 1, wherein the illumination power of the near infrared light is 100-300mW.
4. The method according to claim 1, wherein the Ni (OH) 2 The concentration of the nano particles is 0.05-0.2mg/mL.
5. The method according to claim 1, wherein the Ni (OH) 2 The nanoparticle is D-type, L-type or DL-type.
6. The method according to claim 1, wherein the Ni (OH) 2 The nanometer particle is combined with the ligand of neurite growth inducing factor G1 of neuron cell surface membrane protein specifically, and IGF-1 is produced under the action of near infrared illumination.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9804063D0 (en) * | 1998-11-25 | 1998-11-25 | Peter Eriksson | Medicinal product and method of treatment of conditions affecting neural stem cells or progenitor cells |
| CN113247972A (en) * | 2021-06-16 | 2021-08-13 | 江南大学 | Preparation method and application of nickel hydroxide inorganic nanoparticles with near-infrared region chiral optical activity |
| CN113583959A (en) * | 2021-09-16 | 2021-11-02 | 江南大学 | Method for promoting differentiation of neural stem cells |
| CN114832104A (en) * | 2022-05-30 | 2022-08-02 | 江南大学 | Application of chiral nano bionic photosensitive protein in preparation of medicine for promoting regeneration of damaged neuron axons |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9804063D0 (en) * | 1998-11-25 | 1998-11-25 | Peter Eriksson | Medicinal product and method of treatment of conditions affecting neural stem cells or progenitor cells |
| CN113247972A (en) * | 2021-06-16 | 2021-08-13 | 江南大学 | Preparation method and application of nickel hydroxide inorganic nanoparticles with near-infrared region chiral optical activity |
| CN113583959A (en) * | 2021-09-16 | 2021-11-02 | 江南大学 | Method for promoting differentiation of neural stem cells |
| CN114832104A (en) * | 2022-05-30 | 2022-08-02 | 江南大学 | Application of chiral nano bionic photosensitive protein in preparation of medicine for promoting regeneration of damaged neuron axons |
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