CN110882388A - Ultra-small gold nanoparticles for mitochondrial targeting and rapid renal metabolism of tumor cells - Google Patents
Ultra-small gold nanoparticles for mitochondrial targeting and rapid renal metabolism of tumor cells Download PDFInfo
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- CN110882388A CN110882388A CN201911143808.4A CN201911143808A CN110882388A CN 110882388 A CN110882388 A CN 110882388A CN 201911143808 A CN201911143808 A CN 201911143808A CN 110882388 A CN110882388 A CN 110882388A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The invention discloses an ultra-small gold nanoparticle with tumor cell mitochondrion targeting and rapid kidney clearance characteristics, wherein the diameter of the ultra-small gold nanoparticle is 2.5-5.5 nm, the ultra-small gold nanoparticle is prepared by modifying cell-penetrating peptide on the surface of the gold nanoparticle, and the cell-penetrating peptide consists of a FrFK sequence, a VGPLGV sequence and an EKEKEKEKEKEK sequence. The ultra-small gold nanoparticles have very small size, are beneficial to metabolism through the kidney and have good biological safety. The multifunctional responsive surface is stable under normal physiological conditions, internal mitochondrial targeting molecules are exposed after the multifunctional responsive surface responds to a tumor microenvironment, so that the multifunctional responsive surface is efficiently swallowed by liver tumor cells and is targeted to mitochondria, and the enrichment degree and retention time of gold nanoparticles in tumors are improved; the gold nanoparticles are contacted with the mitochondria, so that the structure and the function of the mitochondria can be more effectively destroyed under the irradiation of radioactive rays, and a better radiotherapy sensitization effect is achieved.
Description
(I) technical field
The invention relates to an ultra-small gold nanoparticle with tumor cell mitochondrion targeting and rapid kidney clearing characteristics, and a preparation method and application thereof.
(II) background of the invention
The role and position of radiation therapy in tumor treatment are increasingly prominent, and the radiation therapy is one of the main means for treating malignant tumors, about 70% of cancer patients need radiation therapy in the process of treating cancer, and about 40% of cancer can be cured by radiation therapy.
Theoretically, high atomic number substances (such as heavy metals like gold) enter tumor tissues and can generate stronger photoelectric absorption in the tumor tissues than surrounding normal tissues, so that more radioactive energy can be transmitted to the tumor tissues, and the effect of radiotherapy sensitization is achieved. The albumin modified nano-gold has obvious sensitization effect on X-ray radiotherapy of liver cancer tumor-bearing mice: under the irradiation dose of 5Gy, the tumor inhibition rate can be improved to 58% from 28% of simple radiotherapy by injecting gold nanospheres with the particle size of 30-60 nm into tail veins, and the sensitization coefficient reaches 2.07.
Although the gold nanoparticles have good biocompatibility, toxic and side effects may be generated if the gold nanoparticles accumulate in important organs in the body; meanwhile, the gold nanoparticles lack the targeting capability of tumors or specific organelles, so that the concentration of the gold nanoparticles in tumor tissues and the action of the gold nanoparticles on the specific organelles are not favorably improved, and the radiotherapy sensitization effect is limited; these disadvantages limit their popularization and application.
The gold nano material with the size less than 5.5nm can be rapidly metabolized through the kidney, so that the accumulation of the nano material in the body is reduced, and the generation of long-term toxicity is avoided. However, such a nano material lacks the targeting function of tumor or organelle, is not favorable for accumulation in tumor tissues and interaction with a specific organelle, and has poor radiotherapy sensitization effect.
The nano material with the tumor microenvironment responsiveness can maintain the surface hydrophilicity and the electrical neutrality in a normal physiological environment, and is beneficial to the in vivo circulation; under the action of specific enzyme in the tumor microenvironment, the hydrophilic molecules on the surface are removed to expose the cell affinity molecules inside, so that the tumor cells can endocytose the hydrophilic molecules and target the hydrophilic molecules to specific organelles, and the concentration of the nano material in tumor tissues and the interaction between the nano material and the specific organelles are improved. The cell-penetrating peptide is a common cell affinity molecule, is modified on the surface of a nano material, and can mediate cell endocytosis. FrFKFrFK, a sequence with a high positive charge that facilitates cell membrane penetration and targeting to mitochondria, has been shown to be effective by several studies. The VGPLGV sequence can be cleaved by Cathepsin, thereby removing the hydrophilic molecules on the surface. EKEKEKEKEKEK is a hydrophilic polypeptide sequence with zwitterion characteristics, and previous researches find that the modification of the polypeptide sequence on the surface of the nanometer material can reduce the protein adsorption and the cell effect and obviously prolong the in vivo circulation time of the nanometer material.
Disclosure of the invention
The invention aims to provide an ultra-small gold nanoparticle with tumor cell mitochondrion targeting and rapid kidney clearing characteristics, a preparation method thereof and application thereof in tumor radiotherapy sensitization.
The technical scheme adopted by the invention is as follows:
an ultra-small gold nanoparticle with tumor cell mitochondrion targeting and rapid kidney clearance characteristics, the diameter is 2.5-5.5 nm, and the ultra-small gold nanoparticle is prepared by modifying cell-penetrating peptide on the surface of the gold nanoparticle, wherein the cell-penetrating peptide mainly comprises FrFK sequence, VGPLGV sequence and EKEKEKEKEKEK sequence. The FrFKFrFK sequence (r represents arginine of type D) in the polypeptide plays a role in cell penetrating membrane and mitochondrion targeting, the VGPLGV sequence plays a role in Cathepsin response, and the EKEKEKEKEKEK sequence plays a role in stabilizing nano materials and resisting phagocytosis of cells.
Preferably, the cell-penetrating peptide sequence is one of the following:
(1)CCEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(2)CEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(3)CVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(4)CEKVFrFKFrFKVGFLGVEKEKEKEKEKEK。
the invention constructs the ultra-small gold nanoparticles with tumor microenvironment responsiveness, and realizes the radiotherapy sensitization effect of tumor treatment through liver cancer tissue enrichment and mitochondrion targeting. The ultra-small size nanoparticles can be rapidly metabolized by the kidneys, improving biosafety.
The present invention also relates to a method for preparing the ultra-small gold nanoparticles, the method comprising:
(1) adding cell-penetrating peptide into chloroauric acid solution, adding excessive sodium borohydride after vigorously stirring for 15-20 minutes at room temperature, and obtaining polypeptide-stable ultra-small gold nanoparticle suspension after vigorously stirring for 0.5-1 hour at room temperature;
(2) and (3) concentrating the obtained ultra-small gold nanoparticle suspension by using a dialysis centrifuge tube with the molecular weight cutoff of 3000Da, removing excessive polypeptide ligand and sodium borohydride, and collecting the gold nanoparticles with the liver cancer targeting and radiotherapy sensitization characteristics.
Preferably, the cell-penetrating peptide sequence is one of the following:
(1)CCEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(2)CEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(3)CVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(4)CEKVFrFKFrFKVGFLGVEKEKEKEKEKEK。
the ratio of the cell-penetrating peptide to the chloroauric acid substance in the step (1) is 1-2: 1.
The concentration of the chloroauric acid in the step (1) is 0.1-5 mmol/L.
The ultra-small gold nanoparticles obtained by the method are stable under normal physiological conditions and can circulate in vivo; when the nano-gold particles reach a liver tumor microenvironment, the internal mitochondrion targeting peptide sequence is exposed under the action of high-concentration Cathepsin, so that the nano-gold particles are efficiently swallowed by liver tumor cells and are targeted to the mitochondrion, and the enrichment degree and the retention time of the nano-gold particles in the tumor are improved. The gold nanoparticles and the mitochondria react, and active oxygen is generated on the surface of the gold nanoparticles under the irradiation of radioactive rays, so that the structure and the function of the mitochondria can be damaged, the effect of radiotherapy is improved, and the effect of sensitizing the radiotherapy is achieved.
The invention also relates to the application of the ultra-small gold nanoparticles in the preparation of a radiotherapy sensitizer.
Specifically, the radiotherapy sensitizer is used for treating liver cancer.
The invention has the following beneficial effects: the ultra-small gold nanoparticles have very small size, are beneficial to metabolism through the kidney and have good biological safety. The multifunctional responsive surface is stable under normal physiological conditions, internal mitochondrial targeting molecules are exposed after the multifunctional responsive surface responds to a tumor microenvironment, so that the multifunctional responsive surface is efficiently swallowed by liver tumor cells and is targeted to mitochondria, and the enrichment degree and retention time of gold nanoparticles in tumors are improved; the gold nanoparticles are contacted with the mitochondria, so that the structure and the function of the mitochondria can be more effectively destroyed under the irradiation of radioactive rays, and a better radiotherapy sensitization effect is achieved.
(IV) description of the drawings
FIG. 1 shows transmission electron micrographs and particle size statistics of gold nanoparticles of the present invention.
FIG. 2 is a graph showing the relationship between the size of gold nanoparticles and the raw material feed ratio.
FIG. 3 is the relationship between the endocytosis of the gold nanoparticles with responsive surface by the hepatoma cells and the incubation time.
FIG. 4 is a tissue distribution of gold nanoparticles with responsive surfaces injected into tumor-bearing mice.
FIG. 5 shows the radiosensitization effect of gold nanoparticles with responsive surface injected into tumor-bearing mice.
FIG. 6 shows the results of the relationship between the size of gold nanoparticles and the polypeptide.
(V) detailed description of the preferred embodiments
The invention will be further described with reference to specific examples, but the scope of the invention is not limited thereto:
example 1:
1) the polypeptide CCEKVFrFKFrFKVGFLGVEEKEKEKEKEKEKEKEKEKEKEKEKEKEKEKEKEKEKEK was added to 10mL of a solution of chloroauric acid (1mM) and vigorously stirred at room temperature for 15 minutes to bring the concentration of the polypeptide to 2 mM. Sodium borohydride was added to bring the concentration to 10 mM. And (3) violently stirring at room temperature for 0.5-1 hour to obtain the polypeptide-stable ultra-small gold nanoparticle suspension. The transmission electron micrograph is shown in FIG. 1.
2) Placing 10mL of the gold nanoparticle suspension obtained in the step 1) into a dialysis centrifuge tube (with the molecular weight cutoff of 3000Da), centrifuging for 10 minutes at 5000 r, collecting the solution containing the excessive polypeptide ligand and sodium borohydride at the bottom of the centrifuge tube, and keeping the ultra-small gold nanoparticles obtained by concentration on the upper part of the centrifuge tube.
3) Co-culturing the gold nanoparticles (Au @ Res Peptide, 100 mu g/mL) obtained in the step 2) and the liver cancer cell HepG2 for 24 hours. Casthepsin was optionally added to the cell culture medium at 5. mu.g/mL, and gold nanoparticles (Au @ No Peptide) with surface-modified non-responsive polypeptide molecules were used as controls. And detecting the concentration of the gold nanoparticles in the liver cancer cells. The results are shown in fig. 3, which shows that gold nanoparticles with responsive surfaces have the highest amount of phagocytosis in the presence of the Casthepsin enzyme.
5) Injecting the gold nanoparticles (Au @ Res Peptide, 5mg/kg) obtained in the step 2) into a tumor-bearing mouse, and detecting the content of the gold nanoparticles in the tumor in the main organ after 12 hours. Results referring to fig. 4, it is shown that a responsive surface can increase the degree of gold nanoparticle enrichment within a tumor. While a relatively high proportion of gold nanoparticles are found in the kidney, indicating that small size favors metabolism of the nanoparticles through the kidney.
6) Injecting the gold nanoparticles (Au @ Res Peptide, 5mg/kg) obtained in the step 2) into a tumor-bearing mouse, and performing 6Gy irradiation treatment after 12 hours. Results referring to fig. 5, it is shown that gold nanoparticles with responsive surfaces can achieve the best radiosensitizing effect.
Example 2:
the difference from example 1 is step 1): the polypeptide CCEKVFrFKFrFrFKVGFLGVEEKEKEKEKEKEKEKEKEKEKEKEKEKEKEKEKEKEKEK was added to 10mL of a chloroauric acid (1mM) solution and vigorously stirred at room temperature for 15 minutes to give a polypeptide concentration of 0.25, 0.5, 1.0, 2.0mM, respectively. Sodium borohydride was added to bring the concentration to 10 mM. And (3) after vigorously stirring for 0.5-1 hour at room temperature, obtaining the polypeptide-stable ultra-small gold nanoparticle suspension prepared under different raw material feeding proportions. The results of the relationship between the size of the gold nanoparticles and the raw material feed ratio are shown in fig. 2. With the increasing of the ratio of the polypeptide to the chloroauric acid, the particle size of the obtained nanogold gradually decreases. Therefore, in order to obtain gold nanoparticles with the particle size of less than 5.5nm, the molar ratio of the polypeptide to the chloroauric acid needs to be 1-2: 1.
Example 3:
the difference from example 1 is step 1): to 10mL of a solution of chloroauric acid (1mM) were added the different polypeptides:
(1)CCEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(2)CEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(3)CVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(4)CEKVFrFKFrFKVGFLGVEKEKEKEKEKEK。
the mixture was stirred vigorously at room temperature for 15 minutes to achieve a polypeptide concentration of 2.0mM each. Sodium borohydride was added to bring the concentration to 10 mM. And (3) violently stirring at room temperature for 0.5-1 hour to obtain the ultra-small gold nanoparticle suspension with different stable polypeptides. The results of the relationship between the size of the gold nanoparticles and the polypeptide are shown in FIG. 6. Therefore, the gold nanoparticles with the particle size of less than 5.5nm can be obtained from 4 polypeptides.
Sequence listing
<110> Zhejiang university
<120> tumor cell mitochondrially targeted and rapid renal metabolism ultra-small gold nanoparticles
<160>4
<170>SIPOSequenceListing 1.0
<210>2
<211>33
<212>PRT
<213> Artificial Sequence (Artificial Sequence)
<400>2
Cys Cys Glu Lys Glu Lys Val Phe Arg Phe Lys Phe Arg Phe Lys Val
1 5 10 15
Gly Phe Leu Gly Val Glu Lys Glu Lys Glu Lys Glu Lys Glu Lys Glu
20 25 30
Lys
<210>2
<211>32
<212>PRT
<213> Artificial Sequence (Artificial Sequence)
<400>2
Cys Glu Lys Glu Lys Val Phe Arg Phe Lys Phe Arg Phe Lys Val Gly
1 5 10 15
Phe Leu Gly Val Glu Lys Glu Lys Glu Lys Glu Lys Glu Lys Glu Lys
20 25 30
<210>3
<211>28
<212>PRT
<213> Artificial Sequence (Artificial Sequence)
<400>3
Cys Val Phe Arg Phe Lys Phe Arg Phe Lys Val Gly Phe Leu Gly Val
1 5 10 15
Glu Lys Glu Lys Glu Lys Glu Lys Glu Lys Glu Lys
20 25
<210>4
<211>30
<212>PRT
<213> Artificial Sequence (Artificial Sequence)
<400>4
Cys Glu Lys Val Phe Arg Phe Lys Phe Arg Phe Lys Val Gly Phe Leu
1 5 10 15
Gly Val Glu Lys Glu Lys Glu Lys Glu Lys Glu Lys Glu Lys
20 25 30
Claims (8)
1. An ultra-small gold nanoparticle with tumor cell mitochondrion targeting and rapid kidney clearance characteristics, the diameter is 2.5-5.5 nm, and the ultra-small gold nanoparticle is prepared by modifying cell-penetrating peptide on the surface of the gold nanoparticle, wherein the cell-penetrating peptide mainly comprises FrFK sequence, VGPLGV sequence and EKEKEKEKEKEK sequence.
2. The ultra-small gold nanoparticles of claim 1, wherein the cell-penetrating peptide sequence is one of:
(1)CCEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(2)CEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(3)CVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(4)CEKVFrFKFrFKVGFLGVEKEKEKEKEKEK。
3. a method of making the ultra-small gold nanoparticles of claim 1, the method comprising:
(1) adding cell-penetrating peptide into chloroauric acid solution, adding excessive sodium borohydride after vigorously stirring for 15-20 minutes at room temperature, and obtaining polypeptide-stable ultra-small gold nanoparticle suspension after vigorously stirring for 0.5-1 hour at room temperature;
(2) and (3) concentrating the obtained ultra-small gold nanoparticle suspension by using a dialysis centrifuge tube with the molecular weight cutoff of 3000Da, removing excessive polypeptide ligand and sodium borohydride, and collecting the gold nanoparticles with the liver cancer targeting and radiotherapy sensitization characteristics.
4. The method of claim 3, wherein the cell-penetrating peptide sequence is one of:
(1)CCEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(2)CEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(3)CVFrFKFrFKVGFLGVEKEKEKEKEKEK；
(4)CEKVFrFKFrFKVGFLGVEKEKEKEKEKEK。
5. the method according to claim 3, wherein the ratio of the amount of cell-penetrating peptide to the amount of chloroauric acid in step (1) is 1-2: 1.
6. The method according to claim 3, wherein the concentration of chloroauric acid in step (1) is 0.1 to 5 mmol/L.
7. The use of the ultra-small gold nanoparticles of claim 1 in the preparation of a radiosensitizer.
8. The use according to claim 7, wherein the radiosensitizer is used to treat liver cancer.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114106108A (en) * | 2021-11-25 | 2022-03-01 | 中国石油大学(华东) | Polypeptide-gold nanoparticle compound, preparation method and application thereof |
| CN115869418A (en) * | 2022-06-24 | 2023-03-31 | 国家纳米科学中心 | Gold nanoparticle for regulating formation of serum protein corona, and preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110075296A (en) * | 2019-03-26 | 2019-08-02 | 浙江大学 | Jenner's popped rice and its preparation and application with hepatoma-targeting and radio therapy sensitization characteristic |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110075296A (en) * | 2019-03-26 | 2019-08-02 | 浙江大学 | Jenner's popped rice and its preparation and application with hepatoma-targeting and radio therapy sensitization characteristic |
Non-Patent Citations (4)
| Title |
|---|
| CHEN ZHOU ET AL.: "Luminescent Gold Nanoparticles with Efficient Renal Clearance", 《ANGEW. CHEM.》 * |
| ILJA TABUJEW ET AL.: "Cell-penetrating peptides for nanomedicine-how to choose the right peptide", 《BIONANOMAT》 * |
| JUE ZHAO ET AL.: "Zwitterionic stealth peptide-protected gold nanoparticles enable long circulation", 《BIOMATERIALS SCIENCE》 * |
| XIAO-DONG ZHANG ET AL.: "Passing through the renal clearance barrier: toward ultrasmall sizes with stable ligands for potential clinical applications", 《INTERNATIONAL JOURNAL OF NANOMEDICINE》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114106108A (en) * | 2021-11-25 | 2022-03-01 | 中国石油大学(华东) | Polypeptide-gold nanoparticle compound, preparation method and application thereof |
| CN114106108B (en) * | 2021-11-25 | 2023-07-14 | 中国石油大学(华东) | Polypeptide-gold nanoparticle composite, preparation method and application thereof |
| CN115869418A (en) * | 2022-06-24 | 2023-03-31 | 国家纳米科学中心 | Gold nanoparticle for regulating formation of serum protein corona, and preparation method and application thereof |
| CN115869418B (en) * | 2022-06-24 | 2024-02-23 | 国家纳米科学中心 | Gold nanoparticle for regulating formation of serum protein corona, preparation method and application thereof |
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