CN113289014B - Zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with ultra-small particle size as well as preparation method and application thereof - Google Patents
Zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with ultra-small particle size as well as preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to a zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with an ultra-small particle size, and a preparation method and application thereof. Dissolving zwitterion polycysteine-g- (2-methacryloyloxyethyl phosphorylcholine) in deionized water, adding an aqueous solution of ferric chloride, and stirring at room temperature to perform a coordination reaction; and adding gallic acid solution into the solution, fully stirring, and dialyzing after the reaction is finished to obtain the zwitter-ion polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size. Compared with the prior art, the preparation reaction condition of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with the ultra-small particle size is mild, the design is reasonable, and the operation is simple and convenient. The zwitter-ion polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size, which are obtained by the invention, can realize photo-thermal-iron death combined treatment and traceless ablation of breast cancer through one-time administration and one-time low-dose 808nm near-infrared illumination, and have important application prospects in breast cancer noninvasive treatment.
Description
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to a zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with an ultra-small particle size, and a preparation method and application thereof.
Background
Iron death is a novel programmed cell death mode, and mainly induces cell death by lipid peroxidation through fenton reaction or ester oxygenase catalysis of highly expressed unsaturated fatty acids on cell membranes. Iron death therapy based on novel nanomaterials has received much attention in cancer therapy due to its unique anti-tumor therapeutic profile. At present, researchers have developed ferromagnetic nanomaterials, iron organic frameworks, iron nanocrystals, iron coordinated nanoparticles, and the like. The iron coordination nanoparticles are expected to deliver iron ions to tumor sites, and the Fenton reaction is accelerated, so that the iron death effect is improved. However, these iron nanomaterials have problems of uncontrollable iron delivery behavior, low fenton reaction activity at the tumor site, poor iron death effect, and risk of in vivo safety.
Therefore, the development of the ultra-small particle size iron nanoparticles with good biocompatibility and high Fenton reaction activity provides a practical and effective way for solving the problems, and has a clinical application prospect of realizing efficient treatment of tumors.
Literature search found that Shao-Kai Sun et al reported on the preparation of iron-Gallic Acid Coordination Polymer Nanonetworks and their performance studies in the title < Functional-Protein-associated organization of Fe-Gallic Acid Coordination Polymer Nanonetworks for Localized Photothermal Therapy > (Yaqiong Wang, Jing Zhang, Chuyu Zhang, Bingjie Li, Jiajio Wang, Xuejun Zhang, Dong Li, and o-Kai Sun, ACS Sustainable sham. Eng, 2019,7, 994. one 1005). However, the above reported method cannot prepare ultra-small particle size and unsaturated iron-coordinated nanoparticles, and the photothermal conversion efficiency is only 20.33%, resulting in low fenton reaction activity and poor iron death therapeutic effect, and also having problems of long-term biosafety, etc., and thus it is difficult to convert and apply in clinic.
Disclosure of Invention
In order to solve the problems that the iron-gallic acid coordination polymer nano network in the prior art can not realize the preparation of ultra-small particle size and unsaturated iron coordination nanoparticles, the photothermal conversion efficiency is low, the Fenton reaction activity is low, the iron death treatment effect is poor, long-term biotoxicity exists and the like, the invention provides the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size, and the preparation method and the application thereof.
The invention designs and synthesizes the zwitterion polypeptide/gallic acid/iron coordination nano particle with ultra-small particle size by utilizing the co-coordination chemical reaction of sulfydryl and hydroxyl and ferric iron, not only successfully avoids the problem of in vivo safety of the traditional nano material (>10nm), but also provides a simple and effective way for a photothermal therapy and iron death cooperative treatment system for tumors.
The preparation reaction condition of the amphoteric ion polypeptide/gallic acid/iron coordination nano particle with the ultra-small particle size is mild, the design is reasonable, and the operation is simple and convenient. The invention provides an experimental platform for constructing the polypeptide nano material with ultra-small particle size, unsaturated iron coordination mode, near infrared absorption, multi-mode imaging, photo-thermal treatment and iron death integration, and has important application prospect in the field of breast cancer noninvasive treatment.
The purpose of the invention can be realized by the following technical scheme:
the invention firstly provides a zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with ultra-small particle size, which is characterized in that the nanoparticle is formed by co-coordination of zwitterionic polycysteine-g- (2-methacryloyloxyethyl phosphorylcholine) and gallic acid with ferric ions.
In one embodiment of the present invention, the number average particle diameter of the nanoparticles is 5 to 8 nm.
The invention also provides a preparation method of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size, which comprises the following steps:
(1) dissolving zwitterion polycysteine-g- (2-methacryloyloxyethyl phosphorylcholine) in deionized water, adding an aqueous solution of ferric chloride, and stirring at room temperature to coordinate;
(2) and adding gallic acid solution into the solution, fully stirring, and dialyzing after the reaction is finished to obtain the zwitter-ion polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size.
In one embodiment of the present invention, the zwitterionic polycysteine-g- (2-methacryloyloxyethyl phosphorylcholine) has the following structural formula:
In one embodiment of the invention, in the step (1), the stirring temperature is 20-25 ℃ and the time is 12-24 h, and the room temperature reaction is preferably 12 h.
In one embodiment of the present invention, in the step (1), the mass ratio of the zwitterionic polycysteine-g- (2-methacryloyloxyethyl phosphorylcholine) aqueous solution to the ferric chloride aqueous solution is 0.625-2.5: 1, preferably 1: 1.
In one embodiment of the invention, the stirring is carried out on a vortex shaker.
In one embodiment of the invention, in the step (2), the stirring temperature is 20-25 ℃ and the time is 1-3 h, and room temperature reaction is preferred for 1 h.
In one embodiment of the present invention, in the step (2), the coordination molar ratio of the ferric ions to the gallic acid is 1 to 3:1, preferably 3: 1. Under the preferred conditions Fe3+Ultra small particles,/GA 3:1The mesoiron ion has an unsaturated mono-coordination mode.
In one embodiment of the present invention, in step (2), the cut-off molecular weight of the dialysis bag used in dialysis is 1000, and the dialysis is performed for 12 to 24 hours in 1000mL of PBS × 2 to 4, preferably for 24 hours in 1000mL of PBS × 2.
The related properties of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with the ultra-small particle size are as follows:
the 808nm near-infrared photothermal conversion efficiency of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with the ultra-small particle size is as high as 59.5%.
The amphoteric ion polypeptide/gallic acid/iron coordination nanoparticle with the ultra-small particle size has multiple imaging capabilities (photothermal imaging, photoacoustic imaging and magnetic resonance imaging).
The invention also provides application of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with the ultra-small particle size, and the application of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with the ultra-small particle size in preparing an anti-tumor nano photothermal therapeutic agent or a tumor nano diagnostic agent.
In one embodiment of the invention, the tumor is selected from breast cancer.
In order to prove the anti-tumor effect of the photothermal therapy-iron death therapy of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size.
In some embodiments of the present invention, the anti-tumor effect of photothermal therapy-iron death therapy possessed by the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles is confirmed by cell experiments.
In some embodiments of the invention, unilucent iron death therapy using the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles of the invention up-regulates the expression of the apoptotic enzyme C-Caspase-3 in breast cancer cells by 44.5% at low doses of near infrared light (808nm, 1W/cm)210min) the expression level of the apoptosis enzyme C-Caspase-3 in the breast cancer cells is further up-regulated by 89.2 percent by the combined treatment of photothermal therapy and iron death, and the cell level proves that light is generatedHyperthermia-the synergistic effect of iron death therapy.
In some embodiments of the invention, using the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles of the invention, unilucent iron death therapy down-regulates the expression level of GPX-4, an iron death marker, in breast cancer cells by 56.0% while photothermal therapy-iron death combination therapy at low doses of near infrared radiation further down-regulates the expression level of GPX-4 in breast cancer cells by 94.7%, further demonstrating the synergistic effect of photothermal therapy-iron death therapy at the cellular level.
In some embodiments of the present invention, the anti-tumor effect of photothermal therapy-iron death therapy possessed by the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles is confirmed by animal experiments.
In some embodiments of the invention, the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles of the invention are administered by single intravenous injection and single low dose light irradiation (808nm, 1W/cm)2And 10min), the temperature of the tumor part of the tumor-bearing mouse is increased to 47.4 ℃, and the photoacoustic signal and the magnetic resonance signal of the tumor part are respectively increased by 5.2 times and 1.0 time after 4 h. Realizes the breast cancer (100 mm) of a nude mouse by one-time administration and one-time low-dose illumination3) The photothermal-iron death combined treatment and the traceless ablation thereof. GPX-4 activity in tumor tissues was down-regulated by 34.5% and 79.5% in the iron-only death treatment group and the combination treatment group, respectively, demonstrating synergy of photothermal therapy and iron death at the animal level.
In the invention, the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle has the characteristics of ultra-small particle size, unsaturated iron coordination mode, intrinsic photo-thermal performance, intracellular acidic pH value responsiveness and the like, is favorable for accelerating Fenton reaction at a tumor part and promoting iron death, thereby realizing the synergistic treatment effect of photo-thermal treatment and iron death of multi-mode imaging guidance (photo-thermal imaging, photo-acoustic imaging and magnetic resonance imaging) and achieving the traceless eradication effect of tumors.
The invention provides a simple and effective new way for obtaining the zwitter-ion polypeptide composite nano particle with ultra-small particle size, unsaturated iron coordination mode, near infrared light absorption, pH responsiveness, multi-mode imaging, photo-thermal treatment and iron death integration and the application of the zwitter-ion polypeptide composite nano particle in a cancer cooperative treatment system.
Compared with the prior art, the invention has the following advantages:
(1) the amphoteric ion polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size are efficiently synthesized, wherein the phosphorylcholine greatly reduces the nonspecific protein adsorption and enhances the stability of the nanomaterial;
(2) the characteristics of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles such as ultra-small particle size, unsaturated iron coordination mode, intrinsic photo-thermal performance, intracellular acidic pH value responsiveness and the like are beneficial to accelerating the Fenton reaction of a tumor part and promoting iron death, so that the synergistic treatment effect of photo-thermal therapy and iron death is realized.
(3) Photothermal imaging, photoacoustic imaging and magnetic resonance imaging of the tumor can be realized through low-dose near-infrared illumination, so that the multi-mode imaging-guided cooperative treatment and traceless eradication of the breast cancer and other tumors are realized.
Drawings
FIG. 1 is a scheme showing the synthesis scheme of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size in example 1;
FIG. 2 is a graph showing the dynamic light scattering of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron complexed nanoparticles of example 1;
FIG. 3 is a temperature rise and fall curve diagram (808nm, 1W/cm) of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticle (1.2mg/mL) in example 1 under three-circle illumination2，10min)；
FIG. 4 is a schematic representation of the in vitro growth inhibitory effect of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron complexed nanoparticles on 4-T1 cells in example 1;
FIG. 5 is a schematic diagram of the expression levels of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with ultra-small particle size in example 1 on C-Caspase-3 and GPX-4 proteins in 4-T1 cells before and after near infrared illumination;
FIG. 6 is a photo-thermal image of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles of example 1;
FIG. 7 is a photo-acoustic image of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles of example 1;
FIG. 8 is a MRI image of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles of example 1;
FIG. 9 is a schematic diagram of the inhibitory effect of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size on the growth of 4-T1 tumor in example 1.
FIG. 10 is a schematic diagram showing the effect of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles on GPX-4 activity of 4-T1 tumor before and after near infrared illumination in example 1.
Detailed Description
The invention is described in detail below with reference to the figures and specific embodiments.
Example 1
Preparation of zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size:
step one, 2mL of zwitterionic poly-cysteine-g- (2-methacryloyloxyethyl phosphorylcholine) aqueous solution (2mg/mL) is taken in a 25mL glass bottle, 100. mu.L of ferric chloride solution (40mg/mL) is slowly added, the solution is diluted to 5mL with deionized water, and the mixture is stirred at room temperature for 12 h.
And step two, adding 50 mu L of gallic acid solution (20mg/mL) into the solution, placing the solution on a vortex oscillator to fully stir for 5min, and then stirring the solution at room temperature to continue the reaction for 1 h. After the reaction, the mixture was dialyzed against 10mmol/L PBS (pH 7.4) for 12h (2 × 1L, MW 1000 in dialysis bag) to obtain zwitterionic polypeptide/gallic acid/iron complex nanoparticles having an ultra-small particle size (the synthesis scheme is shown in fig. 1).
The dynamic light scattering spectrum of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticle prepared in this example is shown in FIG. 2, the number average particle size is 6.6 + -1.0 nm, and the PDI is 0.48 + -0.05.
Example 2
The photo-thermal conversion effect of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles prepared in example 1 was tested.
200. mu.L of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron complex nanoparticle solution (1.2mg/mL) at 1W/cm2The temperature of the solution was recorded at intervals of 30 seconds by a thermocouple probe while irradiating with near infrared light of 808nm, and the temperature of the solution was recorded at intervals of 30 seconds after cutting off the irradiation after 10 minutes. This process was repeated 3 times. The temperature rise and fall curve chart of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle (1.2mg/mL) with ultra-small particle size under three-circle illumination is shown in figure 3, the temperature of the solution rises by about 27 ℃, and the solution has good photo-thermal stability.
Example 3
Experiment on the effect of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticle prepared in example 1 on breast cancer cells in vitro.
The zwitterionic polypeptide/gallic acid/iron coordination nanoparticle (PCGA @ FeNP) with ultra-small particle size prepared in example 1 is prepared by using cell culture solution with the concentration of 2.34, 4.69, 9.38, 18.75, 37.5, 75, 150 and 300 mu g/mL respectively, and then cultured with 4-T1 cells (breast cancer) for 72h or cultured for 12h, and then irradiated by near infrared laser for 10min (808nm, 1W/cm)2) And continuing to culture for 48 hours. The results of the cell activity test by using the MTT method are shown in fig. 4, the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size show good cancer cell killing capability of the iron death therapy, and particularly under the irradiation of near-infrared laser, the nanoparticles can be further promoted to kill cancer cells, so that the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size have good phototherapeutic-iron death synergistic treatment effect.
Example 4
Experiment on the influence of the prepared zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with ultra-small particle size on the expression levels of C-Caspase-3 and GPX-4 proteins in 4-T1 cells before and after near-infrared illumination.
The zwitterionic polypeptide/gallic acid/iron complex nanoparticles (1.2mg/mL) with ultra-small particle size prepared in example 1 were added to a 6-well plateOr further irradiating with light for 10min (808nm, 1W/cm)2) PBS was used as control. Incubation was performed at 37 ℃ for 24h, trypsinized, washed three times with cold PBS, centrifuged at 1000rpm for 10min to collect cells, and suspended in RIPA lysis buffer. The lysate was centrifuged and the supernatant was collected and the protein concentration was determined using BCA protein assay (Thermo Fisher Scientific). Total protein was determined using the dioctadenin protein, and the proteins of each sample were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and then transferred to a polyvinylidene difluoride membrane. After incubation in 2% BSA for 60min, the membranes were incubated with C-Caspase-3 and GPX-4 antibodies overnight at 4 ℃. Subsequently, the membrane was incubated with secondary antibodies at room temperature for 30min, washed three times with TBST, and visualized using a ChemiDoc MP detection system (Bio-Rad). The results are shown in fig. 5, the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size can up-regulate C-Caspase-3 and down-regulate GPX-4 protein, especially under the irradiation of near-infrared laser, can further promote the up-regulation of C-Caspase-3 and the down-regulation of GPX-4 protein, which shows that the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size can induce iron death besides inducing apoptosis, and meanwhile, the photo-thermal can further accelerate Fenton reaction to promote iron death, so that the therapeutic effect of cooperation of photothermal therapy and iron death is good.
Example 5
Photothermographic imaging of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles prepared in example 1;
the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle (3mg/mL) with ultra-small particle size prepared in example 1 was injected into tumor-bearing mice via tail vein, and the tumor site was irradiated with light for 10min (808nm, 1W/cm) 4h after injection2) And imaging the image by using a near-infrared thermal imager. As shown in FIG. 6, the tumor site temperature of the tumor-bearing mice injected with the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles having ultra-small particle sizes increased to 47.4 ℃ while the tumor site temperature of the tumor-bearing mice injected with PBS increased only about 3.5 ℃. Indicates that the zwitter ion polypeptide/gallic acid/iron coordination nano particle with ultra-small particle size passes through near infrared light mediumThe photo-thermal effect can kill cancer cells.
Example 6
Photoacoustic imaging of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles prepared in example 1;
the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle (3mg/mL) with ultra-small particle size prepared in example 1 is injected into a tumor-bearing mouse through tail vein, and the photoacoustic imaging is performed on the tumor-bearing mouse at 0h, 1h, 2h, 4h, 6h, 8h and 12h after injection, and as a result, as shown in FIG. 7, the photoacoustic signal at the tumor part of the tumor-bearing mouse injected with the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with ultra-small particle size is gradually enhanced within the in vivo circulation time, and the photoacoustic signal is strongest at 4h after injection, is 5.2 times higher than 0h, and then is gradually weakened. The zwitter-ion polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size can be greatly enriched at tumor sites and have good photoacoustic imaging capability, so that the zwitter-ion polypeptide/gallic acid/iron coordination nanoparticles are expected to be used for multi-mode imaging-guided accurate cancer treatment.
Example 7
Magnetic resonance imaging of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles prepared in example 1;
the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle (3mg/mL) with ultra-small particle size prepared in example 1 is injected into tumor-bearing mice through tail vein, and the tumor-bearing mice are subjected to magnetic resonance imaging at 0h, 1h, 2h, 4h, 6h, 8h and 12h after injection. The results are shown in fig. 8, the magnetic resonance signals of the tumor part of the tumor-bearing mice injected with the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle sizes are gradually enhanced within the in vivo circulation time, the magnetic resonance signals are strongest after 4h injection and are 1.0 times higher than 0h, and then are gradually weakened. The zwitter-ion polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size can be greatly enriched at tumor sites and have good magnetic resonance imaging capability, so that the zwitter-ion polypeptide/gallic acid/iron coordination nanoparticles are expected to be used for multi-mode imaging-guided accurate cancer treatment.
Example 8
Experiment on the influence of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticle prepared in example 1 on breast cancer growth in vivo.
Mice inoculated with 4-T1 tumor were divided into four groups: PBS, PBS + NIR, zwitterionic polypeptide/gallic acid/iron coordinating nanoparticles (3mg/mL), zwitterionic polypeptide/gallic acid/iron coordinating nanoparticles + NIR (3 mg/mL). Injecting once on day 0, and irradiating PBS + NIR, zwitterionic polypeptide/gallic acid/iron coordination nanoparticle + NIR for 10min (808nm, 1W/cm)2) While mice were weighed and tumor volumes were measured every 1 day. After the treatment, tumors of tumor-bearing mice of each treatment group were harvested on day 16 and analyzed for the iron death marker GPX-4. From the plotted tumor volume curve (fig. 9) it can be found that: the tumors of the PBS, PBS and NIR groups continuously grow, the tumors of the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle group slowly grow, for the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle and NIR, all the mice tumors are completely ablated and do not scar on the 4 th day, and the recurrence phenomenon of the tumors does not appear in the 16-day treatment process. Furthermore, as can be seen from fig. 10, the GPX-4 activity in tumor tissues was down-regulated by 34.5% and 79.5% in the zwitterionic polypeptide/gallic acid/iron coordinating nanoparticle group, zwitterionic polypeptide/gallic acid/iron coordinating nanoparticle + NIR group, respectively. The results show that the amphoteric ion polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size have the synergistic effect of photothermal therapy and iron death, and have a transformation application prospect in noninvasive breast cancer treatment.
The embodiments described above are intended to facilitate a person of ordinary skill in the art in understanding and using the invention. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make modifications and alterations without departing from the scope of the present invention.
Claims (10)
1. A zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with ultra-small particle diameter is characterized in that the nanoparticle is formed by co-coordination of zwitterionic polycysteine-g- (2-methacryloyloxyethyl phosphorylcholine) and gallic acid with ferric ions;
the structural formula of the zwitterionic polycysteine-g- (2-methacryloyloxyethyl phosphorylcholine) is as follows:
2. The zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with ultra-small particle size according to claim 1, wherein the number average particle size of the nanoparticle is 5-8 nm.
3. The method for preparing the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with ultra-small particle size according to claim 1, comprising the steps of:
(1) dissolving zwitterion polycysteine-g- (2-methacryloyloxyethyl phosphorylcholine) in deionized water, adding an aqueous solution of ferric chloride, and stirring at room temperature to coordinate;
(2) and adding gallic acid solution into the solution, fully stirring, and dialyzing after the reaction is finished to obtain the zwitter-ion polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size.
4. The method for preparing the zwitterionic polypeptide/gallic acid/iron coordination nanoparticles with ultra-small particle size according to claim 3, wherein the stirring temperature in step (1) is 20-25 ℃ and the stirring time is 12-24 h.
5. The method for preparing the ultra-small-particle-size zwitterionic polypeptide/gallic acid/iron coordination nanoparticle as claimed in claim 3, wherein in the step (1), the mass ratio of the zwitterionic polycysteine-g- (2-methacryloyloxyethyl phosphorylcholine) aqueous solution to the ferric chloride aqueous solution is 0.625-2.5: 1.
6. The method for preparing the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with the ultra-small particle size according to claim 3, wherein the stirring temperature in the step (2) is 20-25 ℃ and the stirring time is 1-3 h.
7. The method for preparing the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with ultra-small particle size according to claim 3, wherein in the step (2), the coordination molar ratio of ferric ions to gallic acid is 1-3: 1.
8. The method for preparing the zwitterionic polypeptide/gallic acid/iron coordination nanoparticle with the ultra-small particle size according to claim 3, wherein in the step (2), the cut-off molecular weight of a dialysis bag used in dialysis is 1000, and the dialysis is performed for 12-24 h, and the volume of the PBS is 1000mL multiplied by 2-4.
9. The use of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticle of claim 1, wherein said ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticle is used in the preparation of an anti-tumor nano photothermal therapeutic agent.
10. The use of the ultra-small particle size zwitterionic polypeptide/gallic acid/iron coordination nanoparticles according to claim 9 wherein said tumor is selected for breast cancer.
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