CN108853059A - A kind of polypyrrole-polyvinylpyrrolidone nano particle and its preparation method and application - Google Patents
A kind of polypyrrole-polyvinylpyrrolidone nano particle and its preparation method and application Download PDFInfo
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Abstract
A kind of polypyrrole-polyvinylpyrrolidone nano particle, synchronous surface modification polyvinylpyrrolidone forms in pyrroles's polymerization process.Additionally provide the preparation method of above-mentioned nano particle, the polyvinylpyrrolidone of different molecular weight and concentration is separately added into distilled water, initiator is added after stirring and dissolving, add pyrroles, continue stirring to polymerization to complete, centrifuge washing obtains polypyrrole-polyvinylpyrrolidone nano particle of different-grain diameter.Above-mentioned polypyrrole-polyvinylpyrrolidone nano particle is additionally provided as the purposes in pharmaceutical carrier or oncotherapy material.The present invention grafts polyvinylpyrrolidone in nano grain surface, enhances the colloidal stability of nano material, makes it have good blood compatibility and biocompatibility；And the microscopic appearance of polypyrrole nano particle is regulated and controled by the molecular weight of change polyvinylpyrrolidone and concentration, to solve the technical problem in tumor thermotherapy effect.
Description
Technical field
The invention belongs to materialogy fields, are related to a kind of Bio-Nano-Materials, specifically a kind of polypyrrole-polyethylene
Pyrrolidones nano particle and its preparation method and application.
Background technique
The photo-thermal therapy of tumour, i.e. photo-thermal ablation technology, because its minimally invasive and efficient feature receives the wide of people
General concern.The basic principle of photo-thermal therapy is by conjunctive use near-infrared absorption agent and stronger for tissue penetration power
Near infrared light, using photothermal conversion mechanism generate high heat, make tumor tissues local heating, selectively kill tumour it is thin
Born of the same parents.For traditional treatment method, photo-thermal therapy is a kind of green treatment method, shows many advantages.For example,
NIR laser has good biological tissue's penetrability, and during penetrating tissue, the small and normal tissue of light absorption decaying is thin
Cellular damage is smaller；Secondly, photo-thermal therapy embodies great application potential in terms of the accuracy of oncotherapy and controllability.
The premise that NIR laser plays diagnosis and treatment effect is to be required to absorb NIR laser and convert thereof into the nano material of heat, i.e. institute
The optical-thermal conversion material of meaning.In photo-thermal therapy, optical-thermal conversion material passes through active or passive target (i.e. tumor locus blood vessel
High-permeability and anelasticity, enhanced permeability and retention, EPR) effect is enriched in tumor tissues
Place.Under the radiation of NIR laser, it is enriched in the optical-thermal conversion material at tumor tissues and absorbs NIR laser and convert thereof into heat
Amount causes tumour cell position temperature to increase, and then achievees the purpose that ablation and kill tumour cell.It can be seen that photo-thermal is controlled
Two treated are big, and basic key condition is NIR laser and optical-thermal conversion material.
Theoretically, all in the near infrared region to there is light absorpting ability and the preferable nano material of biocompatibility make
It is studied for optical-thermal conversion material for photo-thermal therapy.In recent years, in tumor thermal therapy field, most is in infrared light region
It is widely studied with the nano meter biomaterial (including inorganic material and organic material) absorbed by force.Inorganic material predominantly with
Metal nanoparticle (such as gold nano-material, palladium nano sheet etc.) based on gold, silver, palladium etc. or the semiconductor based on copper are received
Rice material (such as nano copper sulfate particle, copper selenide)；In addition, based on carbon (such as graphene, carbon pipe) inorganic material
The major class optothermal material for being.These materials usually require more complicated preparation process, and there are some functional defects.Example
Such as, pattern variation can occur under illumination condition and cause to absorb offset for gold nanorods, and copper sulphide nano particles are in vivo
It is not easy to be metabolized, the absorption coefficient of light of carbon material is lower, photothermal conversion efficiency is low etc., it limits it and further applies.Organic photo-thermal
Transition material, such as polyaniline, poly- (3,4- ethylidene) poly- (styrene sulfonic acid) (PEDOT：PSS) and polypyrrole (PPy) etc. is because gathering around
There are good biocompatibility, optical stability and excellent photothermal conversion performance to become innovative optical-thermal conversion material.?
In these innovative optical-thermal conversion materials, polypyrrole nano particle of uniform size, which seems, to be even more important.
Polypyrrole (PPy) is a kind of electroconductive polymer being polymerized by five-ring heterocycles, and this material is excellent because of its
Electric conductivity and outstanding environmental stability and be concerned.The position α of pyrrole monomer is suitable with β polymerizing powers, so polymerization
When show as three dimensional growth, therefore the microscopic appearance of PPy is often in cauliflower-shaped or warty.The relatively regular PPy of pattern is obtained, just
There must be the space factor that can control and limit pyrroles's aggregation growth, it can be along being carried out in a certain specific direction or region
Orderly aggregation growth.
Studies have shown that the addition of dopant be capable of providing pyrroles's ordering growth needed for space factor, to be had
The polypyrrole of special microscopic appearance.
Dopant in polypyrrole synthesis mainly has Bronsted acid, surfactant etc..Wherein, surfactant has special
Molecular structure and working mechanism, the three dimensional growth of pyrroles can be limited by being introduced into the synthesis process of polypyrrole, obtain a system
Arrange the PPy with special micro looks.With the development of science and technology, emphasis of the promotion of PPy performance as PPy research, and the property of PPy
It can directly be influenced by its microscopic appearance, therefore seek optimum optimization process conditions to realize the controllability to specific morphology PPy
Preparation becomes the most important thing.
Summary of the invention
For above-mentioned technical problem in the prior art, the present invention provides a kind of polypyrrole-polyvinylpyrrolidones to receive
Rice grain and its preparation method and application, described this polypyrrole-polyvinylpyrrolidone nano particle and preparation method thereof
The technical issues of microscopic appearance that solve polypyrrole nano particle in the prior art with purposes influences tumor thermotherapy effect.
The present invention provides a kind of polypyrrole-polyvinylpyrrolidone nano particles, in the polypyrrole nano particle
Surface modification has polyvinylpyrrolidone.
Further, the molecular weight of the polyvinylpyrrolidone is 40kDa-1300kDa, concentration 1-25mg/mL.
Further, the molecular weight of the polyvinylpyrrolidone is 40kDa, concentration 25mg/mL；Nano particle
Diameter is 74.15nm.
Further, the molecular weight of the polyvinylpyrrolidone is 360kDa, concentration 25mg/mL；Nano particle
Partial size be 74.55nm.
Further, the molecular weight of the polyvinylpyrrolidone is 1300kDa, concentration 25mg/mL；Nano particle
Partial size be 68.98nm.
Further, the molecular weight of the polyvinylpyrrolidone is 360kDa, concentration 5mg/mL；Nano particle
Partial size is 83.79nm.
The present invention also provides a kind of polypyrrole-polyvinylpyrrolidone nano particle preparation methods, including walk as follows
Suddenly：
1) polyvinylpyrrolidone (PVP) is added in distilled water, the molecular weight of the polyvinylpyrrolidone is
Initiator is added after stirring and dissolving so that the concentration of the polyvinylpyrrolidone is 1-25mg/mL in 40kDa-1300kDa,
The initiator is FeCl3·6H2O, any one in ammonium persulfate or potassium permanganate, the initiator after addition
Concentration be 10-100mg/mL；
2) pyrroles is added, the volume ratio of the pyrroles and distilled water is 1:100-1:200,0-4 DEG C at a temperature of,
Stirring to polymerization is completed, and by acquired solution centrifuge washing, obtains polypyrrole-polyvinylpyrrolidone nano particle.
Further, in step 2), the polypyrrole-polyvinylpyrrolidone nano particle diameter is 74.15,
74.55,68.98 or 83.79nm.
Further, step 1) or 2), the mixing time is 10-60 minutes, and the reaction time is 1-8 small
When.
Further, step 1) or 2) in, be washed with distilled water 2~5 times.
The present invention also provides above-mentioned polypyrrole-purposes of the polyvinylpyrrolidone nano particle as pharmaceutical carrier.
The present invention also provides the above-mentioned polypyrrole stated-polyvinylpyrrolidone nano particles as oncotherapy material
In purposes.
The present invention improves polypyrrole nano particle by the method that dopant is added simultaneously in polypyrrole synthesis process
Pattern, synchronous surface modification and its regulation of application performance.Through inventor the study found that passing through the process in chemical oxidising polymerisation
Middle addition PVP, can be made PPy-PVP nano particle；By changing the chain length and concentration of PVP, may be implemented to PPy-PVP
A series of regulation of performances such as nano particle pattern, photothermal conversion efficiency, photo-thermal therapy, drug loading and releasability.
The method control of dopant PVP is added by selecting different initiators in the present invention simultaneously in PPy synthesis process
Pattern, the synchronous surface of PPy nano particle are modified and regulate and control its application performance.
Present invention process is simple, and product is easy to get, and chain length, the concentration by changing PVP can regulate and control PPy-PVP nano particle
A series of performances such as pattern, photothermal conversion efficiency, photo-thermal therapy, drug loading and releasability regulation.It is injected to tumour
Afterwards, PPy-PVP nano particle can be absorbed near infrared light and convert thermal energy for it and make tumor tissues local heating, kill swollen
Oncocyte；The colloidal stability of nano material can be enhanced in nano grain surface grafting PVP, make it have good blood phase
Capacitive and biocompatibility reduce body reticuloendothelial system and swallow to the non-specificity of nano material, keep nano material more
Ground is enriched in tumor region, improves the therapeutic effect to tumour.
By the PPy-PVP of preparation40kDa、PPy-PVP360kDa、PPy-PVP1300kDa(PVP concentration is 25mg/mL), PPy-
PVP360kDa(PVP concentration is 5mg/mL) four kinds of materials are scattered in 0.9% NaCl injection, and the resulting solution of 200uL is led to
Crossing tail vein and being injected into lotus has in the Balb/C nude mouse of 4T1 breast cancer tumour, by power density is 1W/cm after 24 hours2、
The near-infrared laser that wavelength is 808nm irradiates tumour 5 minutes.Experimental result discovery after carrying out laser irradiation, injects PPy-
PVP360kDaDaThe growth of -5mg/mL material group mouse tumor volume is obviously inhibited, and injects PPy- under equal conditions
PVP40kDa、PPy-PVP360kDa、PPy-PVP1300kDa(PVP concentration is 25mg/mL) three kinds of materials and only injection 0.9%
NaCl injection, mouse tumor inhibitory effect is unobvious in group.This is the experimental results showed that PPy- of the present invention
PVP360kDa- 5mg/mL nano particle has good internal antitumous effect, has potential application in fields such as oncotherapies
Prospect.
The present invention is compared with prior art, and technological progress is significant.The present invention is by the anti-of chemical oxidising polymerisation
It answers and PVP is added in system, while synthesizing PPy-PVP nano particle, a step realizes the structure tune to PPy-PVP nano particle
Control and surface PVP modification, and realize to the photo-thermal efficiency of PPy-PVP nano particle, drug loading, inside and outside photo-thermal therapy etc. one
The regulation of serial performance.Unharmful substance generates in reaction process of the invention, and therefore, preparation method of the invention is simply easy
Row, yield are high, are suitble to scale industrial production.
Detailed description of the invention
Fig. 1 (a, b) PPy-PVP40kDaNano particle (partial size 74.15nm), (c, d) PPy-PVP360kDaNano particle (grain
Diameter is 74.55nm), (e, f) PPy-PVP1300kDaNano particle (partial size 68.98nm), (g, h) PPy-PVP360kDa-5mg/mL
The SEM of nano particle (partial size 83.79nm) schemes and its grain size distribution.
Fig. 2 (a), (c), (e), (g) are respectively PPy-PVP40kDa、PPy-PVP360kDa、PPy-PVP1300kDa、PPy-
PVP360kDaFour kinds of nano particles of -5mg/mL are scattered in physiological saline the hydration kinetics diameter for 24 hours, after 48h, 72h.(b),
(d), (f), (h) are scattered in the hydration kinetics diameter in 1640 cell culture mediums for 24 hours, after 48h, 72h.Stand storage
72h, there is no apparent variation occurs for the hydration kinetics diameter of above-mentioned four kinds of PPy-PVP nano particles, it was demonstrated that material has
Good colloidal stability, further to lay a good foundation in living body assessment of levels their photothermal conversion, killing tumour ability.
(concentration of solution is the UV-visible-near infrared absorption of Fig. 3 (a) different-grain diameter PPy-PVP nano particle
25ppm)；(b) various concentration (10ppm, 40ppm) PPy-PVP360kDaThe ultraviolet-visible of -5mg/mL nano particle-near-infrared is inhaled
Receive spectrum.As can be seen that some strength can be absorbed in one timing of solution concentration, the PPy-PVP material of four kinds of different-grain diameters
Wavelength is the near-infrared laser of 808nm, but with PVP molecular weight, the increase of concentration, light absorption is gradually decreased；PPy-
PVP360kDaAbsorption of -5mg/mL the nano particle at 808nm is maximum, thus speculates its near-infrared absorption-thermal transition ability most
By force.
Fig. 4 PPy-PVP360kDa- 5mg/mL nano particle, pure PVP360kDaFourier transform infrared spectroscopy figure.From figure
As can be seen that 1553 are appeared in, 1473,1285,1042,966 and 932-788cm-1The characteristic peak at place corresponds to the C-C in PPy
Conjugation, asymmetric stretching vibration and symmetrical stretching vibration key, C-N stretching vibration, C-H plain bending and C-H annular become.2950,
1646,1490-1450cm-1The vibration peak at place is respectively that the stretching vibration of C-H in PVP, the stretching vibration of C=O, methylene are curved
Qu Zhendong, C-N stretching vibration illustrate during aoxidizing pyrrole monomer oxidation polymerization formation polypyrrole, PVP360kDaStrand is
Successfully it is connected to the surface (3370cm of PPy nano particle-1The peak of left and right is the flexible vibration of O-H in the water of PVP Molecular Adsorption
It is dynamic).
Fig. 5 (a) different-grain diameter PPy-PVP nanoparticulate dispersion is 0.3W/cm in power2808nm laser emission under
Temperature variation curve (distilled water as control)；(b)PPy-PVP360kDaThermal drivers in -5mg/mL nano particle cooling procedure
Linear Fit Chart of the natural logrithm of power to the time (thus can get system time constant is 202.306)；(c) 8 periods 808
PPy-PVP in laser irradiation heating-laser shutdown temperature-fall period360kDaThe temperature change of -5mg/mL nanoparticulate dispersion is illustrated
Scheme (concentration：100ppm, power：2W/cm2)；(d) when material concentration is 100ppm, the dispersion of different-grain diameter PPy-PVP nano particle
Liquid and distilled water are 0.8W/cm in power2808nm laser emission under warm varied curve；(e) for (d) it is corresponding it is infrared heat at
As picture；(f) identical material concentration (50ppm), different-grain diameter PPy-PVP nanoparticulate dispersion are 0.8W/cm in power2's
Warm varied curve under 808nm laser emission；It (g) is (f) corresponding infrared thermal imaging figure.From Fig. 5 (a) as can be seen that laser shines
After penetrating, the temperature of these four materials is increased between 38~50 DEG C from environment temperature (20.6 DEG C), and the temperature difference reaches 17.4~29.4
℃.Under same experiment condition, distilled water heating is not significant (only increasing 3 DEG C).PPy- is calculated by system time constant
PVP40kDa(Sample I)、PPy-PVP360kDa(Sample II)、PPy-PVP1300kDa(Sample III) and PPy-
PVP360kDaThe photothermal conversion efficiency η of -5mg/mL (Sample IV) four kinds of materialsTRespectively 42.49%, 39.87%,
35.60% and 51.61%.Obviously, as the photothermal conversion efficiency of the increase material of PVP molecular weight reduces, and the dense of PVP is reduced
It spends photothermal conversion efficiency to increase, wherein PPy-PVP360kDa- 5mg/mL material photothermal conversion efficiency highest, i.e. photothermal conversion ability
Most preferably.From Fig. 5 (d) as can be seen that as the temperature difference of the increase material dispersion liquid of PVP molecular weight becomes smaller, but reduce the concentration of PVP
The temperature difference increases；Wherein PPy-PVP360kDa- 5mg/mL nanoparticulate dispersion temperature in 5min increases 50 DEG C or so, shows
Optimal near-infrared laser absorption-heat-convertibility energy.In addition, PPy-PVP360kDa- 5mg/mL nano particle shows good
Thermal stability (Fig. 5 (c)) still keeps good photo-thermal to turn by 8 laser irradiation heatings-laser shutdown cooling experimentation
Transducing power, and the temperature change difference in 8 periods is little.
Cell survival rate (b) and (a) after four kinds of PPy-PVP nano particle (concentration 500ppm) processing for 24 hours of Fig. 6 (a)
Corresponding cell Trypan Blue result (1640 cell culture mediums are control).After cell is incubated for 2h from different materials, deposit
Motility rate is 85% or more, it was demonstrated that these four materials have good cell compatibility.
Fig. 7 cellular level photo-thermal therapy effect：It (a) is 1.0W/cm through power2808nm laser emission 5min after mouse
(cell is first through the PPy-PVP of various concentration for the survival rate of breast cancer cell (4T1 cell)360kDaThe processing of -5mg/mL nano particle
For 24 hours, physiological saline is control).It is 1.0W/cm through overpower within the scope of experimental concentration (0-200 μ g/mL)2808nm swash
Light radiation 5min, and continue after cultivating for 24 hours, the survival rate of 4T1 cell is substantially reduced；The concentration of material is higher, raw to 4T1 cell
Long inhibition is more obvious.When the concentration of material is 200ppm, to the inhibition efficiency of tumour more than 90%；(b) laser treatment
The dead/live coloration result (dead cell can be contaminated for red) of cell afterwards, optical microscopy microscopic examination result shows to work as material
Overwhelming majority cell apoptosis, further demonstrates that PPy-PVP when concentration is 100ppm and 200ppm360kDa- 5mg/mL nanometers
Grain has good Vitro Tumor photo-thermal therapy effect.
The hemolysis rate of tetra- kinds of PPy-PVP nano particles of Fig. 8 (material concentration 500ppm, distilled water are control).It incubates jointly
After educating 2h, hemolysis rate under certain experimental concentration 5% hereinafter, do not observe apparent haemolysis, it was demonstrated that this
Four kinds of materials have good blood compatibility, and for Subsequent secure intravenous medical treatment provides guarantee.
The DOX drug loading rate of four kinds of PPy-PVP nano materials of Fig. 9 (a)；(b) DOX drug release patterns.From figure (a)
As can be seen that DOX concentration (100ppm) timing, PPy-PVP subtract the load efficiency of DOX with the increase of PVP molecular weight
It is small, but increased with the reduction of the concentration of PVP；Wherein, PPy-PVP360kDa- 5mg/mL material load rate is up to
26.39%.
As shown in (b) figure, in pH=5.4, T=37 DEG C, pH=7.4, T=37 DEG C, pH=5.4, T=50 DEG C of three groups of experiments
In, work as pH=7.4, at T=37 DEG C, the preparation of drug is 20%, and in pH=7.4, T=50 DEG C, drug it is tired
Product release rate has reached 23%；PH=5.4 is compared, T=50 DEG C, the cumulative release amount of drug reaches 25%.Analysis learns, with
The burst size of the raising of temperature, drug increases；With the reduction of the pH of solution, release amount of medicine increases.And the position of tumor locus
The physiological environment that local environment is a slant acidity is set, the release of drug is more conducive to；And PPy-PVP360kDa-5mg/mL
The photo-thermal of nano material, which absorbs conversion, can be such that tumor locus temperature increases, and promote the release of drug.PPy-PVP360kDa-5mg/mL
Nano material is a kind of controlled release with pH and NIR laser (temperature) double-response characteristic to the release of DOX, this is to more preferable
Ground improves the chemotherapy effect of DOX, and the toxic side effect for reducing DOX in chemotherapy process is most important.
The temperature variation curve of Figure 10 (a) nude mouse tumor；(b) near-infrared laser radiates each time point infrared thermal imaging figure；
(c) tumour relative volume variation diagram；(d) tumor volume change curve.The result shows that blank control group (injecting normal saline, nothing
By whether there is or not apply laser) tumour growth is unaffected；And it is injected intravenously different-grain diameter PPy-PVP nano material and is aided with 808nm
The nude mouse tumor growth of NIR laser irradiation is effectively suppressed.It is similar with the photo-thermal therapy of cellular level, in reduction PVP molecule
Nano particle obtained has preferably in body photothermal conversion effect under amount or concentration conditions.Correspondingly, tumour relative volume increases
Add and slows down；Wherein, PPy-PVP360kDa- 5mg/mL (Sample IV)-DOX nano material shows optimal oncotherapy effect
Fruit.This is because the PPy-PVP nano material for being enriched in tumor locus can effectively absorb NIR and swash under the irradiation of laser
Light, and photothermal conversion is carried out, while the drug release loaded comes out.Under the double action of high temperature and drug, Sample IV-
DOX shows good tumor thermal therapy effect.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, those skilled in the art
Member can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Range.
Embodiment 1
The PVP of molecular weight 40kDa, concentration 25mg/mL are added in distilled water, are added 2.48g's after stirring and dissolving
FeCl3·6H2O.In 4 DEG C of temperature, pyrroles is added and reacts 4h.By acquired solution centrifuge washing, PPy-PVP is obtained40kDaNanometer
Particle (Fig. 1 a, b).With the diameter (at least measuring 50) of Image J 1.40G software measurement nano particle, PPy-PVP40kDaIt receives
The diameter of rice grain is 74.15nm, PVP40kDaAddition effectively improve PPy nano particle colloidal stability (Fig. 2 a,
b)。
Embodiment 2
The PVP of molecular weight 360kDa, concentration 25mg/mL are added in distilled water, are added 2.48g's after stirring and dissolving
FeCl3·6H2O.In 4 DEG C of temperature, pyrroles is added and reacts 4h.By acquired solution centrifuge washing, PPy-PVP is obtained360kDaNanometer
Particle (Fig. 1 c, d).With the diameter (at least measuring 50) of Image J 1.40G software measurement nano particle, PPy-PVP360kDa
The partial size of nano particle is 74.55nm, PVP360kDaAddition effectively improve PPy nano particle colloidal stability (figure
2c、d)。
Embodiment 3
The PVP of molecular weight 1300kDa, concentration 25mg/mL are added in distilled water, are added 2.48g's after stirring and dissolving
FeCl3·6H2O.In 4 DEG C of temperature, pyrroles is added and reacts 4h.By acquired solution centrifuge washing, PPy-PVP is obtained1300kDaNanometer
Particle (Fig. 1 e, f).With the diameter (at least measuring 50) of Image J 1.40G software measurement nano particle, PPy-PVP1300kDa
The partial size of nano particle is 68.98nm, PVP1300kDaAddition effectively improve PPy nano particle colloidal stability (figure
2e、f)。
Embodiment 4
The PVP of molecular weight 360kDa, concentration 5mg/mL are added in distilled water, are added 2.48g's after stirring and dissolving
FeCl3·6H2O.In 4 DEG C of temperature, pyrroles is added and reacts 4h.By acquired solution centrifuge washing, PPy-PVP is obtained360kDa-5mg/
ML nano particle (Fig. 1 g, h).With the diameter (at least measuring 50) of Image J 1.40G software measurement nano particle, PPy-
PVP360kDaThe partial size of -5mg/mL nano particle is 83.79nm, and FTIR result (Fig. 4) shows PVP360kDa- 5mg/mL successfully connects
It connects on the surface of PPy nano particle, and effectively improves the colloidal stability (Fig. 2 g, h) of nano particle.
Embodiment 5
It disperses four kinds of different materials in the culture hole of 96 porocyte culture plates, obtains the suspension with different materials concentration
Liquid.With near-infrared laser (the power density 0.8W/cm of 808nm wavelength2) irradiation various concentration gradient material solution and steaming
Distilled water (blank group) is changed with time situation by FLIR E60 thermal infrared imager recording materials dispersion liquid and distillation coolant-temperature gage
And corresponding infrared thermal imaging photo (Fig. 5 d, e, f, g).For understand four kinds of materials photothermal conversion efficiency, by laser irradiation,
It closes each 5min and obtains temperature variation curve (Fig. 5 a), the system time constant (figure obtained further according to temperature-fall period linear fit
5b), the photothermal conversion efficiency of four kinds of PPy-PVP nano particles may finally be calculated.To detect PVP360kDa- 5mg/mL material
Photo and thermal stability, repeat 8 periods of laser irradiation-closing, record the solution temperature changing value in each period.
As shown in Fig. 5 (a), after laser irradiation, the temperature of these four materials is increased to 38 from environment temperature (20.6 DEG C)~
Between 50 DEG C, the temperature difference reaches 17.4~29.4 DEG C.Under same experiment condition, distilled water heating is not significant (only increasing 3 DEG C).
PPy-PVP can be calculated by system time constant40kDa(Sample I)、PPy-PVP360kDa(Sample II)、PPy-
PVP1300kDa(Sample III) and PPy-PVP360kDaThe light and transformation efficiency η of four kinds of materials of -5mg/mL (Sample IV)TPoint
It Wei 42.49%, 39.87%, 35.60% and 51.61%.Obviously, as the photothermal conversion of the reduction material of PVP molecular weight is imitated
Rate increases, and the concentration photothermal conversion efficiency for reducing PVP is also in increase trend.Wherein, with PPy-PVP360kDa- 5mg/mL material light
Thermal transition efficiency highest, photothermal conversion ability are best (temperature increases 50 DEG C or so in Fig. 5 d, 5min).Same solution concentration, function
Under rate density, the temperature difference with the increase material dispersion liquid of PVP molecular weight becomes smaller, but the concentration temperature difference for reducing PVP increases；It is same
Under power density, the higher material of solution concentration more can carry out photothermal conversion and increase temperature (shown in Fig. 5 d, f).In addition,
PPy-PVP360kDa- 5mg/mL nano particle shows good thermal stability, by 8 laser irradiation heating-laser shutdowns
After temperature-fall period, which still keeps good photothermal conversion ability (Fig. 5 c).
Embodiment 6
It selects L929 cell as sample, the bio-compatible of different-grain diameter PPy-PVP nano particle is verified by CCK-8 method
Property and external photo-thermal therapy tumor effect.Specific step is as follows：Logarithmic phase L929 cell is collected, with the density of 8000 cells/wells
It is inoculated in 96 porocyte culture plates, is placed in CO2After being cultivated for 24 hours in incubator, nano particle is added into each hole and cultivates
24h.According to CCK-8 kit specification, 10 μ L CCK-8 working solutions are added into every hole.Continue after cultivating 1h, utilizes
BioTekDa microplate reader reads the light absorption value at 450nm, influence of the assay various concentration material to the division of L929 cell
(Fig. 6 a).CCK-8 test after, clean each hole 3 times with physiological saline, using phase contrast microscope (Leica DM IL LED,
Germany) observation and L929 cell after PPy-PVP nano material culture for 24 hours microscopic appearance.After taking pictures, add into each hole
Enter 1ml Trypan Blue liquid.Dyeing ten minutes later, is cleaned trypan blue dyeing liquor 3 times with physiological saline, uses microscope observation platform
Expect blue solution to the staining conditions (Fig. 6 b) of cell.
External photo-thermal therapy tumor effect evaluation procedure is as follows：Logarithmic phase 4T1 cell is collected, with the close of 8000 cells/wells
Degree is inoculated in 96 porocyte culture plates, is placed in CO2After cultivating for 24 hours in incubator, being added into each hole, there is best photo-thermal to turn
Change the PPy-PVP of efficiency360kDa- 5mg/mL nano particle continues to cultivate 4h.It is the radiation training of 808nm near-infrared laser beam with wavelength
Plate is supported, every hole radiates 5min, laser intensity 1W/cm2.After continue to be placed in CO2After cultivating for 24 hours in incubator, CCK-8 is used
Kit evaluates the survival rate (Fig. 7 a) of 4T1 cell after laser emission.It is further dyed using dead/live, evaluates material
External photo-thermal therapy tumor effect (Fig. 7 b).
As shown in Figure 6 a, after cell is incubated for for 24 hours jointly from different materials, control group, cell survival rate is 85%
More than, the experiment proves that these four materials all have good cell compatibility.By 808nm laser emission 5min and continue to train
After supporting for 24 hours, the survival rate of 4T1 cell is substantially reduced, and the concentration of material is higher, is more obvious to the inhibition of 4T1 cell growth.
When the concentration of material is 200ppm, to the inhibition efficiency of tumour more than 90%.As shown in Figure 7b, optical microscopy microscopy knot
Fruit shows that most cells are contaminated for red, i.e. cell apoptosis, consistent with CCK-8 experimental result, further demonstrates that
PPy-PVP360kDa- 5mg/mL nano particle has good Vitro Tumor photo-thermal therapy effect.
Embodiment 7
Blood compatibility is that blood exogenous substance or material generate the reaction to meet the requirements, is the application for evaluating material
One great influence index of performance.The blood compatibility of 4 kinds of PPy-PVP nano materials is had rated by experiment in vitro.Experiment
Steps are as follows：The stable Kunming mouse whole blood 2mL of taking heparin, it is (3min, 3000rpm) and heavy with brine red blood cell to be centrifuged
Starch 3 times.By resulting erythrocyte normal saline dilution to 50mL, it is configured to erythrocyte suspension, is placed in 4 DEG C of refrigerators
It is spare.Setting distilled water group is control group.Four kinds of material concentrations of experimental group are 500ppm, by experimental group and erythrocyte suspension
With 0.15mL：The ratio of 0.75mL mixes, and control group distilled water mixes with the centrifugation object of erythrocyte suspension and (is respectively set three
Group parallel laboratory test).Above-mentioned solution is incubated for 2h under the conditions of 37 DEG C, the liquid after incubation is then centrifuged (5min, 5000rpm)
Separate to obtain supernatant.Using light absorption value of the ultraviolet-visible-near infrared spectrometer measurement supernatant at 570nm, (haemolysis is
Haemocyte bursts and releases hemoglobin, and hemoglobin is soluble in physiological saline, and characteristic absorption is shown at 570nm, therefore
Light absorption value at 570nm is directly proportional to the content of hemoglobin in supernatant), the hemolysis rate (HP) of material is obtained by calculation.
As shown in fig. 7, after erythrocyte is incubated for 2h jointly from different materials, control group, material group haemocyte it is molten
Blood rate is not 5% hereinafter, observe apparent haemolysis, it was demonstrated that these four materials have good blood compatibility
Property, for Subsequent secure intravenous medical treatment provides guarantee.
Embodiment 8
Drug loading experiment：1mL chemotherapeutics DOX is added into 4 kinds of PPy-PVP nano materials (500ppm) respectively
The PPy-PVP nano material of carrying medicament can be obtained in (100ppm), stirring (400rpm, for 24 hours).This experiment uses efficient liquid phase
After chromatography (HPLC) measurement load in supernatant DOX concentration, the concentration for being carried on DOX in material can be obtained.Specific behaviour
Making experiment, steps are as follows：The DOX liquid (0ppm, 25ppm, 50ppm, 75ppm, 100ppm) of configuration standard concentration first, upper machine
Test, HPLC test condition：Mobile phase A：Acetonitrile solution (50%)；Mobile phase B：The phosphoric acid solution (50%) of pH=3；Test waves
It is long：425nm；Flow velocity：0.8mL/min.By the PPy-PVP nano material centrifuge separation after load DOX drug, supernatant is taken, on
Machine test concentrations.By experimental calculation drug loading rate, to seek maximum drug loading.
Drug release experiment：3mg load is had to the PPy-PVP of DOX respectively360kDa- 5mg/mL nano material (DOX：100μ
G/ml, PPy-PVP360kDa-5mg/mL：Phosphate buffer solution (PBS, the pH for being marked with 4mL respectively 1mg/ml) are installed on dialysis
=7.4) and in the reaction flask of Acetic acid-sodium acetate (pH=5.4), be respectively placed in 37 DEG C be incubated in 50 DEG C of shaking tables, each group is done
Three Duplicate Samples.At each scheduled time point, after the buffer containing DOX for drawing 1mL, adds 1mL and correspond to the fresh of pH
Buffer solution.The concentration of the DOX of release is determined by HPLC, calculates the accumulative total volume of DOX in different time points.
Embodiment 9
30 healthy nude mices are taken, stochastic averagina is divided into 7 groups (control group 6, other groups equal 4), every nude mice back skin
150 μ L of lower injection contain 1 × 106A 4T1 tumour cell (is scattered in the RPMI-1640 cell culture medium that 150 μ L are free of fetal calf serum
In), continue raising nude mice 2 weeks according to normal process.Disperse the PPy-PVP nano material of different-grain diameter in 0.9% physiology
In salt water (1000ppm), the first six group mouse injects 200 μ L physiological saline, the PPy- of (I.V.) 0.1mL by tail vein respectively
PVP40kDa(Sample I)、PPy-PVP360kDa(Sample II)、PPy-PVP1300kDa(Sample III)、PPy-PVP360kDa-
5mg/mL(Sample IV)、PPy-PVP360kDaDa- 5mg/mL (Sample IV)-DOX, last group pass through intratumor injection
(I.T.)PPy-PVP360kDa-5mg/mL(Sample IV)-DOX.Then, with NIR laser (1W/cm2, wavelength 808nm) shine
Penetrate mouse 5min.The temperature and thermograph of the tumour of every group of mouse are monitored and recorded using FTIR TM E60 thermal infrared imager
(such as Figure 10 a, b).In subsequent mouse breeding process, monitor and record different time points relative tumour volume (V/V0,
Middle V0 represents primary tumor volume) and every mouse appearance of tumors (such as Figure 10 c, d).
As shown in Figure 10, blank control group (injecting normal saline, no matter whether there is or not apply laser) tumour growth is not by obvious
It influences；And be injected intravenously PPy-PVP nano material and be aided with 808nm NIR laser irradiation nude mouse tumor growth effectively pressed down
System.Laser irradiation is imposed, the tumour temperature difference reduces with the increase (5mg/mL and 25mg/mL) of PVP molecular weight and concentration, swells
Tumor inhibitory effect is deteriorated；The Sample IV-DOX for wherein loading DOX is best to mouse tumor therapeutic effect.This is because swashing
Under the irradiation of light, the PPy-PVP nano material for being enriched in tumor locus can effectively absorb NIR laser, and carry out photo-thermal and turn
It changes and generates high temperature and kill tumour.
Claims (11)
1. a kind of polypyrrole-polyvinylpyrrolidone nano particle, it is characterised in that：In the polypyrrole nano grain surface
It is modified with polyvinylpyrrolidone.
2. a kind of polypyrrole-polyvinylpyrrolidone nano particle according to claim 1, it is characterised in that：Described
The molecular weight of polyvinylpyrrolidone is 40kDa-1300kDa, and concentration is 1-25 mg/mL.
3. a kind of polypyrrole-polyvinylpyrrolidone nano particle according to claim 2, it is characterised in that：Described
The molecular weight of polyvinylpyrrolidone is 40kDa, and concentration is 25 mg/mL；The diameter of nano particle is 74.15 nm.
4. a kind of polypyrrole-polyvinylpyrrolidone nano particle according to claim 2, it is characterised in that：Described
The molecular weight of polyvinylpyrrolidone is 360kDa, and concentration is 25 mg/mL；The partial size of nano particle is 74.55 nm.
5. a kind of polypyrrole-polyvinylpyrrolidone nano particle according to claim 2, it is characterised in that：Described
The molecular weight of polyvinylpyrrolidone is 1300kDa, and concentration is 25 mg/mL；The partial size of nano particle is 68.98 nm.
6. a kind of polypyrrole-polyvinylpyrrolidone nano particle according to claim 2, it is characterised in that：Described
The molecular weight of polyvinylpyrrolidone is 360kDa, and concentration is 5 mg/mL；The partial size of nano particle is 83.79 nm.
7. a kind of preparation method of polypyrrole-polyvinylpyrrolidone nano particle described in claim 1, it is characterised in that packet
Include following steps：
1）Polyvinylpyrrolidone is added in distilled water, the molecular weight of the polyvinylpyrrolidone is 40kDa-
Initiator is added after stirring and dissolving so that the concentration of the polyvinylpyrrolidone is 1-25 mg/mL in 1300kDa, described
Initiator be FeCl3·6H2O, any one in ammonium persulfate or potassium permanganate, the initiator is dense after addition
Degree is 10-100 mg/mL；
2）Add pyrroles, the volume ratio of the pyrroles and distilled water is 1:100-1:200, in 0-4oAt a temperature of C, stirring
It is completed to polymerization, by acquired solution centrifuge washing, obtains polypyrrole-polyvinylpyrrolidone nano particle.
8. a kind of preparation method of polypyrrole-polyvinylpyrrolidone nano particle according to claim 7, feature exist
In：The polypyrrole-polyvinylpyrrolidone nano particle diameter is 74.15,74.55,68.98 or 83.79 nm.
9. a kind of preparation method of polypyrrole-polyvinylpyrrolidone nano particle according to claim 7, feature exist
In：Step 1）Or 2）, the mixing time is 10-60 minutes, and the reaction time is 1-8 hours；Step 2）In, with steaming
Distilled water is washed 2 ~ 5 times.
10. polypyrrole described in claim 1-purposes of the polyvinylpyrrolidone nano particle as pharmaceutical carrier.
11. polypyrrole described in claim 1-polyvinylpyrrolidone nano particle is as the purposes in oncotherapy material.
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| CN112156187A (en) * | 2020-11-09 | 2021-01-01 | 上海理工大学 | Preparation method of polypyrrole nanoparticles with adjustable photothermal conversion capacity |
| CN113248731A (en) * | 2021-04-25 | 2021-08-13 | 江苏大学 | PNIPAm/PPy composite hydrogel and preparation method and application thereof |
| CN113248731B (en) * | 2021-04-25 | 2023-12-26 | 江苏大学 | PNIPAm/PPy composite hydrogel and preparation method and application thereof |
| CN113332445A (en) * | 2021-05-13 | 2021-09-03 | 浙江大学杭州国际科创中心 | CaO2Cu-ferrocene multifunctional nano-particles and preparation method thereof |
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| CN113912872A (en) * | 2021-09-14 | 2022-01-11 | 中山大学 | Polypyrrole nanoparticle for copper-induced oxidative polymerization and preparation method and application thereof |
| CN113995837A (en) * | 2021-11-05 | 2022-02-01 | 中国科学院长春应用化学研究所 | Template-free hollow tannic acid-iron nano coordination sphere and preparation method and application thereof |
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