CN109512797A - The preparation method of nano-medicament carrier and products thereof based on metal organic frame - Google Patents
The preparation method of nano-medicament carrier and products thereof based on metal organic frame Download PDFInfo
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Abstract
The present invention relates to a kind of preparation methods for being based on metal organic framework (ZIF-8) new drug carrier, using gold nanorods as seed, on vertex of its surface using Zn atom as frame, by the N atom and Zn composition chemical bond in imidazole ring, one layer of shell with high stability and high porosity is formed；By loading photosensitizer, and then constitute metal organic framework (ZIF-8) new drug carrier.The method of the present invention advantage is: can pass through the draw ratio of regulation Au NRs, the light thermal property of regulating medicine carrier；Regulate and control the thickness and size of ZIF-8 shell by changing molar ratio and reaction time；Promote the dissociation of ZIF-8 shell by the photochemical and thermal reaction of Au NRs, to accelerate the release of photosensitizer, enhances photosensitizer photodynamics effect.The method of the present invention is simple, strong operability, while the pharmaceutical carrier good biocompatibility that the present invention synthesizes, can further satisfaction production and application.
Description
Technical field
The present invention relates to a kind of preparation methods of nano-medicament carrier based on metal organic framework and products thereof and application.
The invention belongs to nano biological medical material fields.
Background technique
As environmental degradation aggravates, global cancer morbidity and death rate presentation steeply rise trend.Treatment of cancer at present
Means mainly have: operation, radiotherapy, chemotherapy and immunotherapy etc..Wherein, chemotherapy is that treating cancer is the most frequently used
Means, but be constrained to the defects such as chemotherapeutic toxicity is larger, and targeting is poor, utilization ratio of drug is low, often caused seriously to patient
Toxic side effect, thus it is often ineffective.Therefore, multifunctional nano pharmaceutical carrier is researched and developed, drug targeting tumor locus is made
Drug controlled release simultaneously, a variety for the treatment of means joints, can significantly reduce the toxic side effect of Nano medication, improve the treatment of cancer
Effect.
Photo-thermal therapy (PTT) and photodynamic therapy (PDT) are as emerging anti-cancer therapies by extensive at present
Concern.PTT generates heat using illumination, is that specimens temperature increases, directly kill cancer cell, mitigates normal tissue
Injury.PDT delivers energy to oxygen using photosensitizer under laser irradiation, generates the very high singlet oxygen of activity, so with life
Oxidation reaction occurs for object molecule, generates cytotoxicity, killing tumor cell.Wherein, gold nanorods (Au NRs) have unique
Surface plasma resonance property (has the horizontal and vertical peak SPR), can match with the optical maser wavelength of near-infrared, make near infrared light
Subcutaneous deep assembling is penetrated, realizes subcutaneous assembling imaging and photo-thermal therapy.Chlorin e 6 (Ce6) is a kind of to be widely used
Chlorophyll family photosensitizer.Ce6 is a kind of amphipathic (water-soluble and fat-soluble) molecule, traditional light some compared to photofrin etc.
Quick dose, penetration into tissue is stronger, while Ce6 has very high singlet oxygen quantum generation rate, has on photodynamic therapy and compares
Good application.
Metal organic frame (MOFs) is a kind of logical by inorganic metal center (metal ion or metal cluster) and organic ligand
Self assembly interconnection is crossed, one kind of formation has the crystalline state porous material of periodic network structure.MOFs material has bigger
Specific surface area, preferable biocompatibility and biodegradable advantage, therefore, in terms of pharmaceutical carrier using great latent
Power.
Therefore, design it is novel prepare gold nanorods, photosensitizer and metal organic frame composite Nano pharmaceutical carrier become obtain
It obtains anticancer drug and cooperates with the key of photo-thermal and photodynamic therapy.
Summary of the invention
The present invention is in view of the shortcomings of the prior art, it is an object of that present invention to provide a kind of nanometer medicine based on metal organic frame
The preparation method of object carrier.
Another object of the present invention is: providing a kind of Nano medication based on metal organic frame of above method preparation
Vector product.
The object of the invention is realized by following proposal: a kind of preparation side of the nano-medicament carrier based on metal organic frame
Method, on vertex of its surface using Zn atom as frame, passes through the N atom and Zn structure in imidazole ring using gold nanorods as seed
At chemical bond, one layer of shell with high stability and high porosity is formed；By loading photosensitizer, and then it is organic to constitute metal
Skeleton (ZIF-8) integrates photo-thermal/photodynamic therapy nano-medicament carrier, includes the following steps:
(1) Au NRs is synthesized: being prepared 0.2 M cetyl trimethylammonium bromide (CTAB) and 0.5 mM chlorauric acid solution, is taken 1.5
0.2 M CTAB solution of ml is slowly stirred dissolution in 37 DEG C, and it is molten that 5 ml, 0.5 mM gold chloride is added after CTAB is completely dissolved
Liquid mixes；The sodium borohydride solution for configuring 2 ml, 0.01 M ice bath takes 0.6 ml to be quickly adding into CTAB- gold chloride mixed liquor
In, be vigorously stirred 3 min, pay attention to avoiding generating whirlpool, solution gradually becomes sepia and obtains seed liquor, be stored at room temperature 2 hours it is standby
With；Growth-promoting media is prepared: preparing 200 ml of CTAB liquid of 0.1 M, 30 DEG C of heating are slowly stirred to obtain CTAB solution, prepare 0.01 M
100 ml of silver nitrate solution take 2 ml AgNO after CTAB is completely dissolved3Solution is added in CTAB solution, uniform stirring
It mixes, the HAuCl of 10ml0.01M is added4Solution stirs and evenly mixs；The ascorbic acid of 5 mL, 0.1 M is prepared, and takes 1.6 ml
Ascorbic acid solution is slowly dropped into above-mentioned solution under stirring well, continues uniform stirring, and solution gradually becomes colourless
Obtain growth-promoting media；The sulfuric acid solution that 4 ml 3% (V/V) are added mixes, and stands 30 min, uniformly instills the seed liquor of certain volume,
Deep claret solution can be obtained in 30 DEG C of reaction 12h, is centrifuged 35 min with 9500 rpm/ min of revolving speed, removes supernatant, precipitating
AuNR, 4 DEG C of preservations；
(2) PVP stablizes Au NRs: CTAB-Au NRs is taken out in the Au NRs solution of storage, 200uL, original liquid concentration is larger, from
The heart 9500rpm, 35min, remove supernatant, and precipitate A u NRs is dissolved in 2ml Q water and obtains Au NRs suspension；Weigh 0.5g
PVP(Mw=30000) ultrasonic dissolution in 10 mL methanol formed homogeneous solution, be added in Au NRs suspension, stir at room temperature
2 hr are mixed, then, by being centrifuged 20min with 8000rpm, PVP is collected and stablizes Au NRs precipitating, sample is redispersed in 4mL first
In alcohol；
(3) one-step synthesis method AuNR@ZIF-8 and load C e-6: the 2MI for weighing certain mass in advance is completely dissolved in 4 mL methanol
In solution；The photosensitizer Ce-6 for weighing certain mass is completely dissolved in 1 mL DMSO and obtains Ce-6 solution；Under room temperature, by 2
4 mL 2MI methanol solutions are added in the methanol solution of mL PVP stable Au NRs, are sufficiently mixed and stir 2 minutes, take 0.5 mL
Above-mentioned mixed liquor is added in Ce-6 solution, is sufficiently mixed under room temperature and is slowly stirred 10 min, then, takes 4 mL Zn
(CH3COO)2Solution is added in above-mentioned mixed solution, is sufficiently mixed under room temperature 1 hour, then with 9500 rpm/min revolving speeds
It is centrifuged 35min and collects product, washed twice with methanol, obtain the surface Au NRs and wrap attached ZIF-8 shell, and load photosensitizer Ce-
6 target product.
Mechanism of the present invention is: with cetyl trimethylammonium bromide (CTAB) for template, being received by gold kind dosage control
The golden stick draw ratio of rice, restores gold chloride (H AuCl using reducing agent4) gold nanorods (Au NRs) is generated as seed, using not
With the 2-methylimidazole (2MI) and zinc acetate (Zn (CH of concentration3COO)2) outside its surface synthesis ZIF-8 metal organic frame
Shell, while in shell synthesis process, attached photosensitizer Ce-6 is wrapped, obtains integrating photo-thermal/photodynamic therapy nanometer medicine
Object carrier.
Wherein, the seed liquor is 0.1-1 mL using volume.
Further, the seed liquor is more preferably 0.5 mL using volume.
The 2MI amount is 0.5-0.9 mg.
Further, the 2MI more preferably measures as 7.125 mg.
The photosensitizer Ce-6 dosage is 5-15 mg.
Zn (the CH3COO)2Dosage be 8-15 mg.
Zn (the CH3COO)2Dosage be more preferably 7.2 mg.
The present invention provides a kind of nano-medicament carrier based on metal organic frame, is prepared according to any of the above-described the method
It obtains.
The present invention is provided using gold nanorods as seed, and attached metal organic frame shell is wrapped on surface and the multi-functional of photosensitizer receives
The preparation method of rice pharmaceutical carrier.This method controls the metal that reaction condition prepares different-thickness in gold nanorods the surface of the seed
Organic frame shell, and using the photosensitizer of the attached various concentration of one-step method packet, to obtain collecting photo-thermal/photodynamic therapy in one
The nano-medicament carrier of body.The multifunctional carrier have good biocompatibility, performance stable, photo-thermal and photodynamics effect compared with
Good feature.
More particularly to using Au NRs as seed, on vertex of its surface using Zn atom as frame, by imidazole ring
N atom and Zn constitute chemical bond, form one layer of shell with high stability and high porosity.By loading photosensitizer,
And then realize the dual activity of nano-carrier photo-thermal and photodynamic therapy.Products therefrom is able to satisfy the demand of clinical application.
The present invention has the advantages that
(1) present invention can pass through the draw ratio of regulation Au NRs, the light thermal property of regulating medicine carrier.
(2) present invention can regulate and control the thickness and size of ZIF-8 shell by changing molar ratio and reaction time.
(3) present invention can promote the dissociation of ZIF-8 shell by the photochemical and thermal reaction of Au NRs, to accelerate photosensitizer
Release enhances photosensitizer photodynamics effect.
(4) preparation method in the present invention is simple, strong operability, while the pharmaceutical carrier bio-compatible that the present invention synthesizes
Property it is good, can further satisfaction production and application.
Detailed description of the invention
Attached drawing 1 is the TEM image of Au NRs prepared by case study on implementation 1；
Attached drawing 2 is the TEM image of multifunctional nano pharmaceutical carrier prepared by case study on implementation 1；
Attached drawing 3 is the TEM image of multifunctional nano pharmaceutical carrier prepared by case study on implementation 2.
Specific embodiment
Below by way of specific embodiment, the technical scheme of the present invention will be further described.Embodiment below is to this
The further explanation of invention, and do not limit the scope of the invention.
Embodiment 1
A kind of preparation method of the nano-medicament carrier based on metal organic frame, using gold nanorods as seed, its surface with
Vertex of the Zn atom as frame constitutes chemical bond by N atom in imidazole ring and Zn, formed one layer have high stability and
The shell of high porosity；By loading photosensitizer, and then the nano-medicament carrier of metal organic framework (ZIF-8) is constituted, by such as
Lower step:
(1) Au NRs is synthesized:
Seed liquor synthesis: 0.2 M CTAB and 0.5 mM chlorauric acid solution are prepared (brown bottle is kept in dark place).Take 1.5 ml 0.2
M CTAB solution is slowly stirred dissolution in 37 DEG C, and the mixing of 5 ml, 0.5 mM chlorauric acid solution is added after CTAB is completely dissolved.
The sodium borohydride solution for configuring 2 ml, 0.01 M ice bath takes 0.6 ml to be quickly adding into CTAB- gold chloride mixed liquor, acutely
3 min(are stirred to pay attention to avoiding generating whirlpool), solution gradually becomes sepia, be stored at room temperature 2 hours it is spare.
Growth-promoting media is prepared: preparing 200 ml of CTAB liquid of 0.1 M, 30 DEG C of heating are slowly stirred dissolution；Prepare 0.01 M's
100 ml(brown bottle of silver nitrate solution is kept in dark place).After CTAB is completely dissolved, 2 ml Ag NO are taken3Solution is added to CTAB
In solution, uniform stirring is mixed.The H AuCl of 10 ml, 0.01 M is added4Solution stirs and evenly mixs；Prepare the anti-of 5 mL, 0.1 M
Bad hematic acid, and 1.6 ml ascorbic acid solutions is taken to be slowly dropped into above-mentioned solution under stirring well, continuation is uniformly stirred
It mixes, solution gradually becomes colourless.The sulfuric acid solution that 4 ml 3% (V/V) are added mixes, and stands 30 min；Uniformly instill 0.5 mL
The synthesis of first step process seed liquor, deep claret solution can be obtained in 30 DEG C of reaction 12h, with 9500 rpm/ min of revolving speed from
35 min of the heart removes supernatant, and precipitate A uNRs, 4 DEG C save, and the TEM image of prepared Au NRs is shown in Fig. 1.
(2) attached ZIF-8 shell is wrapped on the surface Au NRs, and loads photosensitizer Ce-6:
PVP stablizes Au NRs: 200uL CTAB-Au NRs is taken out in the Au NRs solution of storage, with 9500 rpm/ of revolving speed
Min is centrifuged 35 min, removes supernatant, and precipitate A uNR is dissolved in 2ml Q water.Weigh PVP(Mw=30000 0.5g) it is ultrasonic molten
Solution forms homogeneous solution in 10 mL methanol, is added in Au NRs suspension at room temperature, stirs 2 hr.Then, by with
8000rpm is centrifuged 20min, collects PVP and stablizes Au NRs precipitating.Sample is redispersed in 4mL methanol.
One-step synthesis method AuNR@ZIF-8 and load C e-6: the 2-MIM for weighing 7.125 mg in advance is completely dissolved in 4 mL
In methanol solution；The photosensitizer for weighing 6 mg is completely dissolved in 1 mL DMSO；Weigh 7.2 mg Zn (CH3COO)2Sufficiently dissolution
In 4 mL methanol solutions.Under room temperature, 4 mL 2-MIM first are added in the methanol solution of 2 mL PVP stable Au NRs
Alcoholic solution is sufficiently mixed and stirs 2 minutes.Take 0.5 mL Ce-6 solution that appeal mixed liquor is added, it is sufficiently mixed under room temperature
Merging is slowly stirred 10 min.Then, 4 mL Zn (CH are taken3COO)2Solution is added into appeal mixed solution, under room temperature
It is sufficiently mixed 1 hour, product is then collected with 9500 rpm/min revolving speeds centrifugation 35min, is washed twice with methanol, obtains Au
Attached ZIF-8 shell is wrapped on the surface NRs, and loads the target product of photosensitizer Ce-6, prepared multifunctional nano pharmaceutical carrier
TEM image is shown in Fig. 2.
As shown in Figure 1, the size of prepared Au NRs is 40 × 10 nm；From Figure 2 it can be seen that pharmaceutical carrier size is about
120 × 100 nm, the thickness of entire ZIF-8 MOF shell are about 40 nm.
Embodiment 2
A kind of preparation method of the nano-medicament carrier based on metal organic frame, it is approximate with embodiment 1, as follows:
(1) Au NRs is synthesized:
Seed liquor synthesis: 0.2 M CTAB and 0.5 mM chlorauric acid solution are prepared (brown bottle is kept in dark place).Take 1.5 ml 0.2
M CTAB solution is slowly stirred dissolution in 37 DEG C, and the mixing of 5 ml, 0.5 mM chlorauric acid solution is added after CTAB is completely dissolved.
The sodium borohydride solution for configuring 2 ml, 0.01 M ice bath takes 0.6 ml to be quickly adding into CTAB- gold chloride mixed liquor, acutely
3 min(are stirred to pay attention to avoiding generating whirlpool), solution gradually becomes sepia, be stored at room temperature 2 hours it is spare.
Growth-promoting media is prepared: preparing 200 ml of CTAB liquid of 0.1 M, 30 DEG C of heating are slowly stirred dissolution；Prepare 0.01 M's
100 ml(brown bottle of silver nitrate solution is kept in dark place).After CTAB is completely dissolved, 2 ml Ag NO are taken3Solution is added to CTAB
In solution, uniform stirring is mixed.The H AuCl of 10 ml, 0.01 M is added4Solution stirs and evenly mixs；Prepare the anti-of 5 mL, 0.1 M
Bad hematic acid, and 1.6 ml ascorbic acid solutions is taken to be slowly dropped into above-mentioned solution under stirring well, continuation is uniformly stirred
It mixes, solution gradually becomes colourless.The sulfuric acid solution that 4 ml 3% (V/V) are added mixes, and stands 30 min；Uniformly instill 0.5 mL
The synthesis of first step process seed liquor, deep claret solution can be obtained in 30 DEG C of reaction 12h.With 9500 rpm/ min of revolving speed from
35 min of the heart removes supernatant, precipitate A uNR, 4 DEG C of preservations.
(2) attached ZIF-8 shell is wrapped on the surface Au NRs, and loads photosensitizer Ce-6:
PVP stablizes Au NRs: 200 uL CTAB-Au NRs is taken out in the Au NRs solution of storage, with 9500 rpm/ of revolving speed
Min is centrifuged 35 min, removes supernatant, and precipitate A uNR is dissolved in 2ml Q water.Weigh PVP(Mw=30000 0.5g) it is ultrasonic molten
Solution forms homogeneous solution in 10 mL methanol, is added in Au NRs suspension at room temperature, stirs 2 hr.Then, by with
8000rpm is centrifuged 20min, collects PVP and stablizes Au NRs precipitating.Sample is redispersed in 4mL methanol.
One-step synthesis method AuNR@ZIF-8 and load C e-6: the 2-MIM for weighing 8 mg in advance is completely dissolved in 4 mL methanol
In solution；The photosensitizer for weighing 10 mg is completely dissolved in 1 mL DMSO；Weigh 7.2 mg Zn (CH3COO)2It is completely dissolved in 4
In mL methanol solution.Under room temperature, the methanol solution 4 mL 2-MIM methanol of addition of 2 mL PVP stable Au NRs are molten
Liquid is sufficiently mixed and stirs 2 minutes.It takes 0.5 mL Ce-6 solution that appeal mixed liquor is added, is sufficiently mixed under room temperature simultaneously
It is slowly stirred 10 min.Then, 4 mL Zn (CH are taken3COO)2Solution is added into appeal mixed solution, under room temperature sufficiently
Mixing 1 hour then collects product with 9500 rpm/min revolving speeds centrifugation 35min, is washed twice with methanol, obtain Au NRs
Attached ZIF-8 shell is wrapped on surface, and loads the target product of photosensitizer Ce-6, the TEM of the multifunctional nano pharmaceutical carrier of preparation at
As figure is shown in Fig. 3.
As seen from Figure 3, pharmaceutical carrier size is about 200 × 160 nm, and the thickness of entire ZIF-8 MOF shell is about 75
nm。
Embodiment 3
A kind of preparation method of the nano-medicament carrier based on metal organic frame, it is approximate with embodiment 1, as follows:
(1) Au NRs is synthesized:
Seed liquor synthesis: 0.2 M CTAB and 0.5 mM chlorauric acid solution are prepared (brown bottle is kept in dark place).Take 1.5 ml 0.2
M CTAB solution is slowly stirred dissolution in 37 DEG C, and the mixing of 5 ml, 0.5 mM chlorauric acid solution is added after CTAB is completely dissolved.
The sodium borohydride solution for configuring 2 ml, 0.01 M ice bath takes 0.6 ml to be quickly adding into CTAB- gold chloride mixed liquor, acutely
3 min(are stirred to pay attention to avoiding generating whirlpool), solution gradually becomes sepia, be stored at room temperature 2 hours it is spare.
Growth-promoting media is prepared: preparing 200 ml of CTAB liquid of 0.1 M, 30 DEG C of heating are slowly stirred dissolution；Prepare 0.01 M's
100 ml(brown bottle of silver nitrate solution is kept in dark place).After CTAB is completely dissolved, 2 ml Ag NO are taken3Solution is added to CTAB
In solution, uniform stirring is mixed.The H AuCl of 10 ml, 0.01 M is added4Solution stirs and evenly mixs；Prepare the anti-of 5 mL, 0.1 M
Bad hematic acid, and 1.6 ml ascorbic acid solutions is taken to be slowly dropped into above-mentioned solution under stirring well, continuation is uniformly stirred
It mixes, solution gradually becomes colourless.The sulfuric acid solution that 4 ml 3% (V/V) are added mixes, and stands 30 min；Uniformly instill 0.2 mL
The synthesis of first step process seed liquor, deep claret solution can be obtained in 30 DEG C of reaction 12h.With 9500 rpm/ min of revolving speed from
35 min of the heart removes supernatant, precipitate A uNR, 4 DEG C of preservations.
(2) attached ZIF-8 shell is wrapped on the surface Au NRs, and loads photosensitizer Ce-6:
PVP stablizes Au NRs: 200uL CTAB-Au NRs is taken out in the Au NRs solution of storage, with 9500 rpm/ of revolving speed
Min is centrifuged 35 min, removes supernatant, and precipitate A uNR is dissolved in 2ml Q water.Weigh PVP(Mw=30000 0.5g) it is ultrasonic molten
Solution forms homogeneous solution in 10 mL methanol, is added in Au NRs suspension at room temperature, stirs 2 hr.Then, by with
8000rpm is centrifuged 20min, collects PVP and stablizes Au NRs precipitating.Sample is redispersed in 4mL methanol.
One-step synthesis method AuNR@ZIF-8 and load C e-6: the 2-MIM for weighing 7.125 mg in advance is completely dissolved in 4 mL
In methanol solution；The photosensitizer for weighing 10 mg is completely dissolved in 1 mL DMSO；Weigh 7.2 mg Zn (CH3COO)2It is sufficiently molten
Solution is in 4 mL methanol solutions.Under room temperature, 4 mL 2-MIM are added in the methanol solution of 2 mL PVP stable Au NRs
Methanol solution is sufficiently mixed and stirs 2 minutes.Take 0.5 mL Ce-6 solution that appeal mixed liquor is added, under room temperature sufficiently
It mixes and is slowly stirred 10 min.Then, 4 mL Zn (CH are taken3COO)2Solution is added into appeal mixed solution, room temperature condition
Under be sufficiently mixed 1 hour, product is then collected with 9500 rpm/min revolving speeds centrifugation 35min, is washed twice with methanol, obtains Au
Attached ZIF-8 shell is wrapped on the surface NRs, and loads the target product of photosensitizer Ce-6.
Embodiment 4
A kind of preparation method of the nano-medicament carrier based on metal organic frame, it is approximate with embodiment 1, as follows:
(1) Au NRs is synthesized:
Seed liquor synthesis: 0.2 M CTAB and 0.5 mM chlorauric acid solution are prepared (brown bottle is kept in dark place).Take 1.5 ml 0.2
M CTAB solution is slowly stirred dissolution in 37 DEG C, and the mixing of 5 ml, 0.5 mM chlorauric acid solution is added after CTAB is completely dissolved.
The sodium borohydride solution for configuring 2 ml, 0.01 M ice bath takes 0.6 ml to be quickly adding into CTAB- gold chloride mixed liquor, acutely
3 min(are stirred to pay attention to avoiding generating whirlpool), solution gradually becomes sepia, be stored at room temperature 2 hours it is spare.
Growth-promoting media is prepared: preparing 200 ml of CTAB liquid of 0.1 M, 30 DEG C of heating are slowly stirred dissolution；Prepare 0.01 M's
100 ml(brown bottle of silver nitrate solution is kept in dark place).After CTAB is completely dissolved, 2 ml Ag NO are taken3Solution is added to CTAB
In solution, uniform stirring is mixed.The H AuCl of 10 ml, 0.01 M is added4Solution stirs and evenly mixs；Prepare the anti-of 5 mL, 0.1 M
Bad hematic acid, and 1.6 ml ascorbic acid solutions is taken to be slowly dropped into above-mentioned solution under stirring well, continuation is uniformly stirred
It mixes, solution gradually becomes colourless.The sulfuric acid solution that 4 ml 3% (V/V) are added mixes, and stands 30 min；Uniformly instill 1 mL's
Deep claret solution can be obtained in the seed liquor of first step process synthesis, 30 DEG C of reaction 12h.With 9500 rpm/ min of revolving speed centrifugation
35 min remove supernatant, precipitate A uNR, 4 DEG C of preservations.
(2) attached ZIF-8 shell is wrapped on the surface Au NRs, and loads photosensitizer Ce-6:
PVP stablizes Au NRs: 200uL CTAB-Au NRs is taken out in the Au NRs solution of storage, with 9500 rpm/ of revolving speed
Min is centrifuged 35 min, removes supernatant, and precipitate A uNR is dissolved in 2ml Q water.Weigh PVP(Mw=30000 0.5g) it is ultrasonic molten
Solution forms homogeneous solution in 10 mL methanol, is added in Au NRs suspension at room temperature, stirs 2 hr.Then, by with
8000rpm is centrifuged 20min, collects PVP and stablizes Au NRs precipitating.Sample is redispersed in 4mL methanol.
One-step synthesis method AuNR@ZIF-8 and load C e-6: the 2-MIM for weighing 7.125 mg in advance is completely dissolved in 4 mL
In methanol solution；The photosensitizer for weighing 10 mg is completely dissolved in 1 mL DMSO；Weigh 7.2 mg Zn (CH3COO)2It is sufficiently molten
Solution is in 4 mL methanol solutions.Under room temperature, 4 mL 2-MIM are added in the methanol solution of 2 mL PVP stable Au NRs
Methanol solution is sufficiently mixed and stirs 2 minutes.Take 0.5 mL Ce-6 solution that appeal mixed liquor is added, under room temperature sufficiently
It mixes and is slowly stirred 10 min.Then, 4 mL Zn (CH are taken3COO)2Solution is added into appeal mixed solution, room temperature condition
Under be sufficiently mixed 1 hour, product is then collected with 9500 rpm/min revolving speeds centrifugation 35min, is washed twice with methanol, obtains Au
Attached ZIF-8 shell is wrapped on the surface NRs, and loads the target product of photosensitizer Ce-6.
Claims (9)
1. a kind of preparation method of the nano-medicament carrier based on metal organic frame, which is characterized in that with gold nanorods be kind
Son forms one layer by the N atom and Zn composition chemical bond in imidazole ring on vertex of its surface using Zn atom as frame
Shell with high stability and high porosity；By loading photosensitizer, and then constitute the nanometer of metal organic framework (ZIF-8)
Pharmaceutical carrier includes the following steps:
(1) Au NRs is synthesized: being prepared 0.2 M cetyl trimethylammonium bromide (CTAB) and 0.5 mM chlorauric acid solution, is taken 1.5
0.2 M CTAB solution of ml is slowly stirred in 37 DEG C, and it is mixed that 5 ml, 0.5 mM chlorauric acid solution is added after CTAB is completely dissolved
It is even to obtain CTAB- gold chloride mixed liquor；The sodium borohydride solution for configuring 2 ml, 0.01 M ice bath, takes 0.6 ml to be quickly adding into
In CTAB- gold chloride mixed liquor, be vigorously stirred 3 min, until solution gradually becomes sepia, be stored at room temperature 2 hours it is spare, must plant
Sub- liquid；Growth-promoting media is prepared: preparing 200 ml of CTAB liquid of 0.1 M, 30 DEG C of heating are slowly stirred dissolution；Prepare the nitre of 0.01 M
Acid silver 100 ml of solution takes 2 ml Ag NO after CTAB is completely dissolved3Solution is added in CTAB solution, and uniform stirring is mixed
It is even, the H AuCl of 10 ml, 0.01 M is added4Solution stirs and evenly mixs to obtain growth-promoting media；The ascorbic acid of 5 mL, 0.1 M is prepared, and
It takes 1.6 ml ascorbic acid solutions to be slowly dropped into above-mentioned growth-promoting media under stirring well, continues uniform stirring, solution
Gradually become colourless, the sulfuric acid solution that 4 ml 3% (V/V) are added mixes, and stands 30 min；Uniformly instill the kind of certain volume
Deep claret solution can be obtained in sub- liquid, 30 DEG C of reaction 12h, is centrifuged 35 min with 9500 rpm/ min of revolving speed, removes supernatant,
Precipitate A uNR, 4 DEG C of preservation Au NRs solution；
(2) PVP stablizes Au NRs:PVP and stablizes Au NRs: CTAB-Au NRs, 200uL are taken out in the Au NRs solution of storage,
Original liquid concentration is larger, is centrifuged 9500rpm, 35min, removes supernatant, precipitate A u NRs, and being dissolved in 2ml Q water, to obtain Au NRs outstanding
Supernatant liquid；Weigh PVP(Mw=30000 0.5g) ultrasonic dissolution in 10 mL methanol formed homogeneous solution, be added to Au at room temperature
In NRs suspension, 2 hr are stirred, then, by being centrifuged 20min with 8000rpm, PVP is collected and stablizes Au NRs precipitating, by sample
It is redispersed in 4mL methanol；
(3) one-step synthesis method AuNR@ZIF-8 and load C e-6: the 2MI for weighing certain mass in advance is completely dissolved in 4 mL methanol
In solution；The photosensitizer Ce-6 for weighing certain mass is completely dissolved in 1 mL DMSO and obtains Ce-6 solution；Under room temperature, by 2
4 mL 2MI methanol solutions are added in the methanol solution of mL PVP stable Au NRs, are sufficiently mixed and stir 2 minutes, take 0.5 mL
Above-mentioned mixed liquor is added in Ce-6 solution, is sufficiently mixed under room temperature and is slowly stirred 10 min, then, takes 4 mL Zn
(CH3COO)2Solution is added in above-mentioned mixed solution, is sufficiently mixed under room temperature 1 hour, then with 9500 rpm/min revolving speeds
It is centrifuged 35min and collects product, washed twice with methanol, obtain the surface Au NRs and wrap attached ZIF-8 shell, and load photosensitizer Ce-
6 target product.
2. preparation method according to claim 1, it is characterised in that the seed liquor is 0.1-1 mL using volume.
3. preparation method according to claim 2, it is characterised in that the seed liquor is more preferably 0.5 using volume
mL。
4. preparation method according to claim 1, it is characterised in that the 2MI amount is 0.5-0.9 mg.
5. the preparation method according to claim 4, it is characterised in that the 2MI amount is 7.125 mg.
6. preparation method according to claim 1, it is characterised in that the photosensitizer Ce-6 dosage is 5-15 mg.
7. preparation method according to claim 1, it is characterised in that the Zn (CH3COO)2Dosage be 8-15 mg.
8. preparation method according to claim 7, it is characterised in that the Zn (CH3COO)2Dosage be more preferably
7.2 mg。
9. a kind of nano-medicament carrier based on metal organic frame, it is characterised in that -8 any side according to claim 1
Method is prepared.
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