CN115708895A - Intraocular lens material and preparation method and application thereof - Google Patents
Intraocular lens material and preparation method and application thereof Download PDFInfo
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- CN115708895A CN115708895A CN202211551843.1A CN202211551843A CN115708895A CN 115708895 A CN115708895 A CN 115708895A CN 202211551843 A CN202211551843 A CN 202211551843A CN 115708895 A CN115708895 A CN 115708895A
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- cadmium
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Abstract
The application relates to the technical field of nano materials and the field of biomedical treatment, in particular to an intraocular lens material and a preparation method and application thereof. An artificial lens material, wherein MXene which is wrapped by photoresponsive mesoporous silica and loaded with a cell proliferation inhibitor and cadmium or nickel element is coated on the rear surface of an optical area of an artificial lens. The artificial lens material prepared by the preparation method is applied to the preparation of materials for treating or preventing after cataract. The application realizes the prevention and treatment of the after-cataract by the photothermal therapy and the drug sustained-release two-in-one therapy by coating the back surface of the optical area of the artificial lens with the MXene which is wrapped by the photoresponsive mesoporous silica and is loaded with the cell proliferation inhibitor and the cadmium or nickel element, and has high biocompatibility.
Description
Technical Field
The application relates to the technical field of nano materials and the field of biomedical treatment, in particular to an intraocular lens material and a preparation method and application thereof.
Background
Posterior Cataract (PCO) is the most common complication affecting vision after cataract extraction in combination with intraocular lens implantation surgery. Its incidence is 30-50% in adults (within 5 years), with about 20-30% of patients becoming blind again due to PCO and 43% requiring re-surgical treatment due to PCO. The incidence rate of PCO in children reaches 100 percent.
After cataract removal, an intraocular lens is implanted within the remaining lens capsule to restore the patient's postoperative visual function. However, a part of the intraocular lens remaining in the anterior capsule proliferates under the stimulation of postoperative inflammatory reaction, creeps between the posterior capsule of the lens and the posterior surface of the intraocular lens through epithelial mesenchymal transition, causing refractive interstitial opacification and posterior capsule shrinkage. The appearance of PCO causes a secondary loss of visual function and requires further treatment, such as post-laser capsulotomy. Laser treatment is costly and also presents risks after surgery.
The modes of controlling PCO are generally: design of intraocular lens, modified surgical technique, laser posterior capsulotomy, physical and chemical means. At present, physical and chemical methods are hot spots in the research of PCO prevention and treatment.
The physical modes comprise the removal of lens epithelial cells remained on the capsular sac during or after the operation as far as possible, high osmotic pressure treatment, photothermal treatment and the like. Chemical means include treatment with various cell proliferation inhibitors both intraoperatively and postoperatively. Nevertheless, the effective control efficiency of PCO is still not ideal, and no effective control method for PCO is available in clinical practice.
Chemical drugs are another common way to control PCO. Chemical drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs), e.g., COX-1 or COX-2 inhibitors, 5-fluorouracil (5-FU), methotrexate (MTX), epidermal growth factor inhibitors, e.g., gefitinib, erlotinib, cyclosporin A (CsA), tacrolimus, rapamycin, paclitaxel, ROCK signal pathway inhibitors, transforming growth factor beta (TGF-beta) inhibitors, and/or siRNA and miRNA of the above signal molecules, and the like, can be administered by various administration modes, such as topical eye drop therapy, intra-operative anterior chamber injection, infusion, and intraocular sustained release with an intraocular lens as a carrier, to achieve the prevention and treatment of PCO. Part of the medicines can achieve the effect of delaying the PCO course.
In the prior art, photothermal therapy is another PCO prevention and treatment mode with application prospect. Photothermal therapy is based on a light conversion agent, which can efficiently convert light energy into heat energy under laser irradiation of a specific wavelength to kill tissue cells at high temperature. However, the effective rate of the current photothermal therapy for preventing and treating PCO is only about 60 percent according to the report of the literature. In summary, neither pharmacotherapy nor photothermal therapy is effective in preventing PCO.
The reasons why the PCO cannot be effectively prevented by the drug therapy and the photothermal therapy are summarized as follows: (1) Cell proliferation inhibitors coated on the surface of IOLs in various ways cannot maintain sustained release of the drug for a long time, and after a period of time, the proliferation efficacy of anti-lens epithelial cells disappears; (2) The cell killing effect of the medicine and the toxic effect of the medicine on intraocular tissues are difficult to balance, and intraocular side effects are easy to cause; (3) The photosensitizer is coated on the annular outer edge of the side surface of the artificial lens, so that after 808nm infrared light is irradiated, the temperature is gradually decreased from the outer edge to the center of the artificial lens, the temperature in the central range is less than 42-45 ℃, an effective killing effect cannot be achieved, and the visual axis area is turbid; (4) When cells are killed by the photo-thermal effect, local inflammatory reaction can be caused, and inflammatory mediators can further stimulate proliferation and migration of lens epithelial cells and promote formation of PCO.
The applicant filed an invention patent application in 2020, publication No. CN114618019A, describing dip coating of silver doped MXene drug loaded material onto the posterior surface of intraocular lenses to obtain self-sterilizing intraocular lenses. However, the method has unsatisfactory effects in terms of drug loading and drug loading stability.
Disclosure of Invention
The invention provides an artificial lens material, wherein a light-responsive mesoporous silica wrapped MXene loaded with a cell proliferation inhibitor and a cadmium or nickel element is coated on the rear surface of an optical zone of an artificial lens.
The photosensitizer photoresponsive mesoporous silica with high light transmission and high photothermal conversion efficiency is loaded on the back surface of the artificial lens, and a cell proliferation inhibitor is also loaded, so that the inflammatory reaction caused by photothermal action is further reduced, the prevention and treatment efficiency of PCO is improved, and the photothermal treatment and the medicine slow release prevention and treatment of PCO are realized.
The artificial lens material, preferably the cell proliferation inhibitor is a non-steroidal anti-inflammatory drug. The non-steroidal anti-inflammatory drug can be COX-1 inhibitor, COX-2 inhibitor, 5-fluorouracil, methotrexate, epidermal growth factor inhibitor gefitinib or erlotinib, cyclosporine A, tacrolimus, rapamycin, paclitaxel, ROCK signaling pathway inhibitor, transforming growth factor beta inhibitor and/or siRNA or miRNA thereof.
The mass ratio of the optical response mesoporous silica to MXene loaded with a cell proliferation inhibitor and doped with cadmium or nickel elements is preferably 0.5
The mass ratio of the cell proliferation inhibitor to MXene doped with cadmium or nickel elements in the artificial lens material is 0.84.
The molar ratio of the doped cadmium or nickel element to MXene of the intraocular lens material is 0.005-0.05:1, preferably 0.01 to 0.02:1, most preferably in a ratio of 0.01:1.
the preparation method of the artificial lens material comprises the following steps:
(1) Carrying out polyethylene glycol surface modification on MXene doped with cadmium or nickel elements, then carrying out covalent bonding by using RGD polypeptide, and adding a cell proliferation inhibitor load to obtain MXene loaded with the cell proliferation inhibitor; (2) Mixing MXene loaded with a cell proliferation inhibitor with the photo-responsive mesoporous silica, adding deionized water, and stirring to obtain MXene coated with the photo-responsive mesoporous silica and loaded with the cell proliferation inhibitor;
(3) MXene which is wrapped by light-responsive mesoporous silica and loaded with a cell proliferation inhibitor is coated on the back surface of the optical area of the artificial lens.
The MXene doped with cadmium or nickel element is obtained by the following steps:
(1) Preparing MAX phase precursor: adding metal powder represented by M, aluminum powder represented by A and carbide or nitride powder corresponding to M in MAX phase into a ball milling device in proportion for grinding, adding excessive aluminum powder, sufficiently grinding, transferring into an alumina crucible, covering with a graphite foil, putting into a tube furnace, and heating and reacting under inert atmosphere to obtain Al-M n+1 AX n Sintering blocks;
(2) Mixing Al-M n+1 AX n Agglomerate filling machineGrinding to obtain precursor phase powder, soaking in hydrochloric acid, washing with deionized water to remove excessive metal elements, taking out precipitate, and drying in vacuum drying oven to obtain Al-M n+ 1 AX n A phase powder;
(3) Molten salt etching of Al-M n+1 AX n Phase powder to obtain cadmium or nickel element doped MXene: taking out the dried Al-MAX, putting the dried Al-MAX, cadmium chloride or nickel chloride, sodium chloride and potassium chloride into a ball milling device for full grinding, putting the ground mixed powder into an alumina crucible, putting the alumina crucible into a tubular furnace, reacting at a high temperature under an inert atmosphere, washing a reaction product with hydrochloric acid after the reaction is finished, filtering out a solvent, taking a precipitate, and adding deionized water for ultrasonic oscillation. And then repeatedly centrifugally cleaning the mixed solution by using deionized water to obtain the MXene material doped with cadmium or nickel elements.
The molar ratio of the MAX, cadmium chloride or nickel chloride, naCl and KCl is 1-6; the temperature of the tubular furnace is 550-850 ℃, and the reaction time is 4-10 hours.
Preferably, the photo-responsive mesoporous silica is obtained by:
mixing dodecanol, sodium hydroxide, hexadecyl trimethyl ammonium bromide and deionized water, heating and stirring uniformly to obtain a mixed solution, dropwise adding tetraethoxysilane into the mixed solution, heating for reaction, centrifugally collecting a reaction product, washing, centrifuging again, and drying a precipitate in vacuum to obtain the catalyst.
The artificial lens material is applied to the preparation of materials for treating or preventing after cataract.
The application realizes the prevention and treatment of the after-cataract by the photothermal therapy and the drug sustained-release two-in-one therapy by coating the back surface of the optical area of the artificial lens with the MXene which is wrapped by the photoresponsive mesoporous silica and is loaded with the cell proliferation inhibitor and the cadmium or nickel element, and has high biocompatibility.
By utilizing the photodynamic therapy of MXene coated by the photoresponsive mesoporous silica and loaded with the cell proliferation inhibitor and the cadmium or nickel element, the infrared light irradiation has effective killing effect, and simultaneously, the drug release is accurately controlled, so that the effective drug concentration is maintained for a longer time, the curative effect is improved, and the toxic and side effects are reduced.
The light-responsive mesoporous silica coated MXene loaded with the cell proliferation inhibitor and the cadmium or nickel element does not influence the light transmittance and the refractive index of the intraocular lens, and has practical application value.
Drawings
FIG. 1 shows different Ti loadings 3 C 2 Intraocular lens appearance of light responsive rapamycin at concentrations (0 μ g/ml to 500 μ g/ml);
FIG. 2 is a graph of the photo-controlled cumulative release of rapamycin;
figure 3 is a graphical representation of PCO after one month implantation of differently treated coated lenses in rabbit eyes.
Detailed Description
The embodiment provides an artificial lens material, wherein a light-responsive mesoporous silica-wrapped MXene loaded with a cell proliferation inhibitor and doped with cadmium or nickel elements is coated on the rear surface of an optical zone of the artificial lens.
MXene is a graphene-like structure obtained by MAX phase processing. The specific molecular formula of the MAX phase is M n+1 AX n (n =1,2or 3), wherein M refers to a transition metal of the first group, such as Sc, ti, zr, V, nb, cr or Mo; a is an Al element, and X is a C and/or N element. As M-X has stronger bond energy and A has more active chemical activity, A can be removed from the MAX phase through etching, and the 2D structure MXene similar to graphene can be obtained. And doping cadmium salt or nickel salt when etching the MAX by using a molten salt method to obtain the cadmium or nickel element doped MXene.
The MXene doped with cadmium or nickel element can be obtained by the following steps:
(1) Preparing MAX phase precursor: adding metal powder represented by M, aluminum powder represented by A and carbide or nitride powder corresponding to M in MAX phase into a ball milling device in proportion for grinding, adding excessive aluminum powder, sufficiently grinding, transferring into an alumina crucible, covering with a graphite foil, putting into a tube furnace, and heating and reacting under inert atmosphere to obtain Al-M n+1 AX n ；
The specific operation can be as follows: the metal powder represented by M, the carbide or nitride powder corresponding to M, and the aluminum powder were ground using a ball mill in a ratio of 1. The ball milled precursor powder was then loaded into an alumina crucible, covered with graphite foil, and then placed into a tube furnace. Purging the furnace with argon at room temperature for 30 minutes, heating the powder to 1380 ℃ and maintaining it at about 100sccm argon for 2 hours;
transition metals include, but are not limited to, sc, ti, V, cr, zr, nb, hf, ta. The corresponding mass ratio is 1. The MAX phase ceramics produced contain, but are not limited to, ti 2 AlC、Ti 2 AlN、V 2 AlC、V 2 AlN、Nb 2 AlC、Nb 2 AlN、Ta 2 AlC、Ti 3 AlC 2 、Ti 3 AlN 2 、V 3 AlC 2 、Ta 3 AlC 2 、Ta 3 AlN 2 、Ti 4 AlC 3 、Ti 4 AlN 3 、Ta 4 AlC 3 、Ta 4 NAl 3 、Nb 4 AlC 3 Any one or a combination of two or more MAX phase ceramics;
(2) Mixing Al-M n+1 AX n Fully grinding the sintered cake to obtain MAX phase powder, then washing and filtering the MAX phase powder by using hydrochloric acid and deionized water through a vacuum filtration device in sequence to remove excessive metal elements, and taking out the precipitate after cleaning and placing the precipitate in a vacuum drying oven for drying;
hydrochloric acid can be washed with 9M HCl until no bubbles are formed, typically 500ml of 9MHCl is sufficient to wash 50-60g of Al-M n+1 AX n； The temperature of vacuum drying can be 80 ℃;
(3) Etching MAX by a molten salt method to obtain MXene doped with cadmium or nickel elements: taking out the dried MAX, putting the MAX and cadmium chloride or nickel chloride, sodium chloride and potassium chloride into a ball milling device for full grinding, putting the ground mixed powder into an alumina crucible, putting the alumina crucible into a tubular furnace, reacting at high temperature under an inert atmosphere, washing a reaction product after the reaction is finished by hydrochloric acid, filtering out a solvent, taking out a precipitate, and adding deionized water for ultrasonic oscillation. And then repeatedly carrying out centrifugal cleaning by using deionized water to obtain the MXene material doped with cadmium or nickel element.
The molar ratio of the doped cadmium or nickel element to MXene is 0.005-0.05:1, preferably 0.01 to 0.02:1, most preferably in a ratio of 0.01:1.
the molar ratio of the MAX, cadmium chloride or nickel chloride, naCl and KCl is 1-6; the temperature of the tubular furnace is 550-850 ℃, and the reaction time is 4-10 hours.
The cell proliferation inhibitor is non-steroidal anti-inflammatory drug, such as COX-1 or COX-2 inhibitor, 5-fluorouracil (5-FU), methotrexate (MTX), epidermal growth factor inhibitor (e.g., gefitinib, erlotinib, cyclosporin A (CSA), tacrolimus, rapamycin, paclitaxel, ROCK signal pathway inhibitor, transforming growth factor beta (TGF-beta) inhibitor, and/or siRNA and miRNA of the above signal molecules. This is not particularly required in this embodiment, and any clinically usable nsaid can be used in the present application. Rapamycin is preferably used.
The intraocular lens used may be hydrophobic acrylates, acrylate hydrogels, silicone gels, silicone hydrogels, fluorosilicone acrylates, polystyrene and polymethylmethacrylate, polycarbonate, polysiloxane, and/or mixtures thereof, and the like, which are not specifically required in this embodiment, as long as clinically useful intraocular lenses can be used in the present application.
The used light-responsive mesoporous silica is wrapped by MXene loaded with a cell proliferation inhibitor and cadmium or nickel element, wherein the mass ratio of the light-responsive mesoporous silica to the MXene loaded with the cell proliferation inhibitor and the cadmium or nickel element is in the range from 0.02 to 1, the preferable ratio is in the range from 0.2 to 0.6. The different mass ratios of the photoresponsive mesoporous silica to MXene loaded with a cell proliferation inhibitor and doped with cadmium or nickel elements can influence the inhibition efficiency of the drug-loaded intraocular lens on the proliferation of residual lens epithelial cells in the capsular bag. When the mass ratio of the photoresponsive mesoporous silica to MXene loaded with a cell proliferation inhibitor and doped with cadmium or nickel elements is less than 0.02. When the mass ratio of the photoresponsive mesoporous silica to the MXene loaded with the cell proliferation inhibitor and doped with cadmium or nickel elements is more than 1. When the mass ratio of the photoresponsive mesoporous silica to MXene loaded with a cell proliferation inhibitor and doped with cadmium or nickel elements is in the range of 0.2-0.6.
The used MXene loaded with the cell proliferation inhibitor and the cadmium or nickel element-doped MXene has a mass ratio of the cell proliferation inhibitor to the cadmium or nickel element-doped MXene ranging from 0.1 to 1.5, preferably ranging from 0.4 to 1, and preferably ranging from 0.84. The MXene performance can be enhanced by doping corresponding metal elements such as cadmium or nickel into the MXene material. The enhancement effect is mainly reflected in the photo-thermal property and high sensitivity of the MXene material, and is more beneficial to realizing various applications such as photo-thermal tumor treatment, photodynamic treatment, photo-thermal drug release and the like.
The preparation method of the intraocular lens material in the embodiment comprises the following steps:
(1) Carrying out polyethylene glycol surface modification on MXene doped with cadmium or nickel elements, carrying out covalent bonding by using arginine-glycine-aspartic acid (Arg-Gly-Asp, RGD) peptide, and adding a cell proliferation inhibitor for loading to obtain the MXene loaded with the cell proliferation inhibitor;
(2) Mixing MXene loaded with a cell proliferation inhibitor with the photo-responsive mesoporous silica, adding deionized water, and stirring to obtain MXene coated with the photo-responsive mesoporous silica and loaded with the cell proliferation inhibitor;
(3) Mixing MXene loaded with a cell proliferation inhibitor with the photo-responsive mesoporous silica, adding deionized water, and stirring, wherein the MXene material has electrostatic adsorption property and can be adsorbed with the photo-responsive mesoporous silica to form MXene coated with the photo-responsive mesoporous silica and loaded with the cell proliferation inhibitor;
(4) The stirring speed can be 2000-3000 r/min, and the stirring time can be 24h;
(5) Coating MXene which is wrapped by light-responsive mesoporous silica and loaded with a cell proliferation inhibitor on the back surface of an optical area of the intraocular lens;
(6) Sealing the anterior surface, lateral surfaces and lens loop of the optic zone of the intraocular lens with adhesive tape, leaving only the posterior surface of the optic zone of the lens exposed to air, and applying O to the intraocular lens 2 And (3) carrying out plasma treatment for 5min, immersing the artificial lens in a Gemini surfactant for full combination, mixing the artificial lens with the MXene wrapped by the photoresponsive mesoporous silica and loaded with the cell proliferation inhibitor, and fixing the MXene wrapped by the photoresponsive mesoporous silica and loaded with the cell proliferation inhibitor to the rear surface of the optical area of the artificial lens.
The photoresponsive mesoporous silica is obtained by the following steps:
mixing dodecanol, sodium hydroxide, hexadecyl trimethyl ammonium bromide and deionized water, heating and stirring uniformly to obtain a mixed solution, dropwise adding tetraethoxysilane into the mixed solution, heating for reaction, centrifugally collecting a reaction product, washing, centrifuging again, and drying a precipitate in vacuum to obtain the catalyst.
The specific operation can be as follows: a round bottom flask was charged with 20mg dodecanol, 30mg sodium hydroxide, 0.1g CTAB (cetyltrimethylammonium bromide) and 50mL deionized water, mixed, heated to 60 deg.C and stirred for 0.5h. Then 0.75ml TEOS (tetraethyl orthosilicate) was added dropwise to the solution using a constant pressure dropping funnel and stirred at 60 ℃ for 2 hours to allow the TEOS to react completely. The reaction product was collected by centrifugation, washed with ethanol and centrifuged again. Repeating for four times to remove CTAB and dodecanol, and vacuum drying the precipitate.
The artificial lens material prepared by the method can be used for preparing a material for treating or preventing after cataract.
Two specific working examples are provided below in the order of material preparation, and the working examples are only used for explaining the scheme of the present application and are not intended to limit the scheme of the present application to the working examples.
Operation example 1
Firstly, adding Ti, tiC and Al into a ball mill according to the mass ratio of 1. Purging with argon gas at room temperature for 30min, heating to 1380 deg.C, and cooling at a rate of 3 deg.C/min; cooling to room temperature, soaking and washing with 9M hydrochloric acid until no bubbles are generated, vacuum filtering with a vacuum filtration device, washing with deionized water, vacuum filtering, drying the obtained precipitate in a vacuum drying oven at 80 deg.C for at least 6 hr to obtain Al-Ti 3 AlC 2 ；
Al-Ti 3 AlC 2 Adding cadmium chloride, sodium chloride and potassium chloride into a ball milling device according to a molar ratio of 1; taking out the reaction product, soaking for 1 hour by using 10% dilute hydrochloric acid, filtering out the solution by using a vacuum filtration device, washing by using deionized water, taking out the precipitate, adding the deionized water, and ultrasonically oscillating for 1 hour. Then repeatedly centrifugally cleaning with deionized water until the pH of supernatant is 6, and finally centrifuging once again to obtain Ti doped with cadmium element 3 C 2 A material;
the obtained Ti 3 C 2 The material is subjected to polyethylene glycol surface modification, then RGD polypeptide is used for covalent bonding, and cell proliferation inhibitor (rapamycin) load is added, so that cell proliferation inhibitor (rapamycin) loaded Ti can be obtained 3 C 2 A nanomaterial;
a round bottom flask was charged with 20mg dodecanol, 30mg sodium hydroxide, 0.1g CTAB (cetyltrimethylammonium bromide) and 50mL deionized water, mixed, heated to 60 deg.C and stirred for 0.5h. Then 0.75ml TEOS (tetraethyl orthosilicate) was added dropwise to the solution using a constant pressure dropping funnel, and stirred at 60 ℃ for 2 hours to completely react TEOS. The reaction product was collected by centrifugation, washed with ethanol and centrifuged again. Repeating the step of removing CTAB and dodecanol for four times, and finally carrying out vacuum drying on the precipitate to obtain the photoresponsive mesoporous silica;
ti to be loaded with cell proliferation inhibitor (rapamycin) 3 C 2 The nanometer material and the photoresponsive mesoporous silica are mixed, added with deionized water and stirred for 24 hours at 2000 r/min, and can be adsorbed with the photoresponsive mesoporous silica to form Ti wrapped by the photoresponsive mesoporous silica due to the electrostatic adsorption property of MXene material 3 C 2 And (3) preparing a system.
Finally, the anterior surface, the lateral surfaces and the lens haptics of the optic zone of the intraocular lens are sealed with adhesive tape, leaving only the posterior surface of the optic zone of the lens exposed to air, and the intraocular lens is sealed with O 2 Treating with plasma for 5min, soaking in Gemini surfactant for full combination, and adding Ti loaded with medicine 3 C 2 The composite material is applied to the posterior surface of the intraocular lens.
Operation example 2
Firstly, adding V, al and C into a ball mill according to the atomic ratio of 2 to 1.5 for grinding, grinding at 400rpm for 18h, fully grinding, transferring into an alumina crucible, covering with graphite foil, and putting into a tube furnace. Cleaning the furnace with argon gas at room temperature for 30min, heating to 1500 deg.C, and heating and cooling at 5 deg.C/min; cooling to room temperature, soaking and washing with 9M hydrochloric acid until no bubbles are generated, vacuum filtering with a vacuum filtration device, washing with deionized water, filtering, drying the obtained precipitate in a vacuum drying oven at 60 deg.C for at least 6 hr to obtain V with excessive Al 2 AlC；
Al-V 2 Adding AlC, nickel chloride, sodium chloride and potassium chloride into a ball milling device according to a molar ratio of 1; taking out the reaction product, soaking for 1 hour by using 10% dilute hydrochloric acid, filtering out the solution by using a vacuum filtration device, washing by using deionized water, taking out the precipitate, adding the deionized water, and ultrasonically oscillating for 1 hour. Then repeatedly centrifugally cleaning with deionized water until the pH of supernatant is 6, and finally centrifuging once again to obtain the nickel-doped V 2 C, material;
subjecting the obtained V to 2 C materialPerforming polyethylene glycol surface modification, performing covalent bonding by RGD polypeptide, and adding cell proliferation inhibitor (rapamycin) to obtain V loaded with cell proliferation inhibitor (rapamycin) 2 C, nano material;
a round bottom flask was charged with 20mg dodecanol, 30mg sodium hydroxide, 0.1g CTAB (cetyltrimethylammonium bromide), and 50mL deionized water, mixed, heated to 60 ℃ and stirred for 0.5h. Then 0.75ml TEOS (tetraethyl orthosilicate) was added dropwise to the solution using a constant pressure dropping funnel and stirred at 60 ℃ for 2 hours to allow the TEOS to react completely. The reaction product was collected by centrifugation, washed with ethanol and centrifuged again. Repeating the step of removing CTAB and dodecanol for four times, and finally carrying out vacuum drying on the precipitate to obtain the photoresponsive mesoporous silica;
v to be loaded with cell proliferation inhibitor (rapamycin) 2 The C nano material and the light responsive mesoporous silica are mixed, deionized water is added into the mixture, and the mixture is stirred for 24 hours at 2000 r/min, and the MXene material has electrostatic adsorption property and can be adsorbed with the light responsive mesoporous silica to form V wrapped by the light responsive mesoporous silica 2 And C, system.
Finally, the anterior surface, the lateral surfaces and the lens haptics of the optic zone of the intraocular lens are sealed with adhesive tape, leaving only the posterior surface of the optic zone of the lens exposed to air, and the intraocular lens is sealed with O 2 Treating with plasma for 5min, soaking in Gemini surfactant for full combination, and loading medicine-loaded V 2 The C composite material is coated on the back surface of the artificial lens.
Operation example 3
Grinding Ti, tiC and Al at the mass ratio of 1 3 AlC 2 ；
Mixing Al-Ti 3 AlC 2 And fully grinding cadmium chloride, sodium chloride and potassium chloride according to a molar ratio of 1 3 C 2 Materials (mass ratio)0.6) to 1), mixing the obtained Ti 3 C 2 The material is modified on the surface by polyethylene glycol, and rapamycin load (rapamycin and Ti) is added 3 C 2 The mass ratio of the materials is 0.84 3 C 2 Nano material, cadmium-doped element and Ti 3 C 2 In a molar ratio of 0.01:1;
adding the obtained material into dodecanol, sodium hydroxide, CTAB (cetyl trimethyl ammonium bromide) and deionized water, mixing, centrifuging, removing CTAB and dodecanol, and finally vacuum-drying the precipitate to obtain the photoresponsive mesoporous silica.
Ti to be loaded with rapamycin 3 C 2 Mixing the nano material with the photo-responsive mesoporous silica, adding deionized water, stirring at 2000 r/min for 24h, and stirring with Ti 3 C 2 The electrostatic adsorption property of the nano material and the light-responsive mesoporous silica are adsorbed to form the light-responsive mesoporous silica-coated rapamycin-loaded Ti 3 C 2 And (3) preparing a system. Rapamycin-loaded Ti coated by controlling photoresponsive mesoporous silica 3 C 2 The addition amount of the system obtains Ti with different concentrations 3 C 2 (0. Mu.g/ml-500. Mu.g/ml) of an intraocular lens.
Finally, the haptics are sealed with tape and the intraocular lens is sealed with O 2 Treating with plasma for 5min, soaking in Gemini surfactant for full combination, and adding Ti loaded with medicine 3 C 2 The composite material is coated on the surface of the optical area of the artificial lens. FIG. 1 shows different Ti loadings 3 C 2 Intraocular lens appearance of concentration light responsive rapamycin.
Effect test
1. 50. Mu.g/ml Ti obtained in working example 3 was added 3 C 2 Intraocular lens with light responsive rapamycin at 808nm NIR (near Infrared laser) at 1.0Wcm -2 Power, cumulative release profile of rapamycin after 10min of irradiation. As can be seen from FIG. 2, the cumulative release rate of rapamycin after 3 cycles of light exposure was 74.1%. 48 hour release of rapamycin from an artificial lens without lightThe amount was only 19.6%. Thus, the novel intraocular lens obtained in working example 3 can realize the light-controlled release of rapamycin.
2. 50. Mu.g/ml Ti obtained in operation example 3 3 C 2 The marking code of the artificial lens of the photoresponse rapamycin is' element doping Rapa @ Ti 3 C 2 -IOL”，
Compared with the operation example 3, the etching process does not add cadmium chloride, and cadmium element doping is not formed, so that Rapa @ Ti is obtained 3 C 2 -IOL”
Doping artificial lens' element with Rapa @ Ti 3 C 2 IOL "with" Rapa @ Ti 3 C 2 IOLs at 808nm NIR (near Infrared laser), respectively, at 1.0Wcm -2 Power, irradiating once a week for 10min each time to obtain' element doped Rapa @ Ti 3 C 2 IOL + Laser "and" Rapa @ Ti 3 C 2 -IOL+Laser”。
Commercial intraocular lenses (C-IOLs), "Rapa @ Ti 3 C 2 -IOL”、“Rapa@Ti 3 C 2 IOL + Laser "," elemental doping Rapa @ Ti 3 C 2 IOL "," elemental doped Rapa @ Ti 3 C 2 IOL + Laser "were implanted in rabbit eyes separately, and after one month, the effect of inhibiting PCO was observed.
Wherein the IOL is an artificial lens, the Rapa is rapamycin, and the Laser is infrared Laser.
As can be seen from FIG. 3, in 1 month of follow-up, the Ti-carrying cadmium element was doped 3 C 2 Artificial lens' element doping Rapa @ Ti of photoresponse rapamycin 3 C 2 After an IOL + Laser test, the PCO formation of rabbit eyes can be effectively inhibited through a high-efficiency photothermal effect and the light-operated release of rapamycin.
The scope of the present invention is not limited thereto, and any person skilled in the art can easily conceive various equivalent modifications or substitutions within the technical scope of the present invention, and these modifications or substitutions should be covered within the scope of the present invention.
Claims (10)
1. An artificial lens material is characterized in that the rear surface of an optical area of an artificial lens is coated with MXene which is wrapped by photoresponsive mesoporous silica and loaded with a cell proliferation inhibitor and cadmium or nickel element.
2. Intraocular lens material according to claim 1, characterized in that the intraocular lens material according to claim 1 is characterized in that the cell proliferation inhibitor is a non-steroidal anti-inflammatory drug.
3. Intraocular lens material according to claim 2, characterized in that the non-steroidal anti-inflammatory drug is a COX-1 inhibitor, a COX-2 inhibitor, 5-fluorouracil, methotrexate, epidermal growth factor inhibitor gefitinib or erlotinib, cyclosporin a, tacrolimus, rapamycin, paclitaxel, ROCK signaling pathway inhibitor, transforming growth factor β inhibitor and/or siRNA or miRNA thereof.
4. Intraocular lens material according to claim 1, characterized in that the mass ratio of photo-responsive mesoporous silica to MXene loaded with cell proliferation inhibitor, cadmium or nickel elements is 0.2-1.
5. Intraocular lens material according to claim 1, characterized in that the mass ratio of inhibitor of cell proliferation to cadmium or nickel element doped MXene is 0.1-1.5.
6. Intraocular lens material according to claim 1, characterized in that the molar ratio of doped cadmium or nickel elements to MXene is 0.005-0.05:1.
7. a method of making an intraocular lens material according to any one of claims 1 to 6, characterized by the steps of:
(1) Carrying out polyethylene glycol surface modification on MXene doped with cadmium or nickel elements, then carrying out covalent bonding by RGD polypeptide, and adding a cell proliferation inhibitor for loading to obtain MXene loaded with the cell proliferation inhibitor;
(2) Mixing MXene loaded with a cell proliferation inhibitor with the photo-responsive mesoporous silica, adding deionized water, and stirring to obtain MXene coated with the photo-responsive mesoporous silica and loaded with the cell proliferation inhibitor;
(3) MXene coated by light-responsive mesoporous silica and loaded with a cell proliferation inhibitor is coated on the back surface of the optical area of the artificial lens.
8. Method for the production of an intraocular lens material according to claim 7, characterized in that MXene doped with cadmium or nickel elements is obtained by the following steps:
(1) Preparing MAX phase precursor: adding metal powder represented by M, aluminum powder represented by A and carbide or nitride powder corresponding to M in MAX phase into a ball milling device in proportion for grinding, adding excessive aluminum powder, sufficiently grinding, transferring into an alumina crucible, covering with a graphite foil, putting into a tube furnace, and heating and reacting under inert atmosphere to obtain Al-M n+1 AX n Sintering blocks;
(2) Mixing Al-M n+1 AX n Fully grinding the sintered block to obtain precursor phase powder, then soaking in hydrochloric acid, washing with deionized water to remove excessive metal elements, taking out the precipitate after washing, and drying in a vacuum drying oven to obtain Al-M n+1 AX n A phase powder;
(3) Molten salt etching of Al-M n+1 AX n Phase powder to obtain cadmium or nickel element doped MXene: taking out the dried Al-MAX, putting the dried Al-MAX, cadmium chloride or nickel chloride, sodium chloride and potassium chloride into a ball milling device for full grinding, putting the ground mixed powder into an alumina crucible, putting the alumina crucible into a tubular furnace, reacting at a high temperature in an inert atmosphere, washing a reaction product with hydrochloric acid after the reaction is finished, filtering out a solvent, taking a precipitate, and adding deionized water for ultrasonic oscillation. And then repeatedly centrifugally cleaning the mixed solution by using deionized water to obtain the MXene material doped with cadmium or nickel elements.
9. The process according to claim 8, wherein the molar ratio of MAX, cadmium chloride or nickel chloride, naCl and KCl is 1; the temperature of the tubular furnace is 550-850 ℃, and the reaction time is 4-10 hours.
10. Use of the intraocular lens material according to any one of claims 1 to 6 or the intraocular lens material obtained by the production method according to any one of claims 7 to 9 for the production of a material for the treatment or prevention of after-cataract.
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