CN112656959A - Se @ SiO2@MnO2-ICG nano composite and preparation method and application thereof - Google Patents
Se @ SiO2@MnO2-ICG nano composite and preparation method and application thereof Download PDFInfo
- Publication number
- CN112656959A CN112656959A CN202011268834.2A CN202011268834A CN112656959A CN 112656959 A CN112656959 A CN 112656959A CN 202011268834 A CN202011268834 A CN 202011268834A CN 112656959 A CN112656959 A CN 112656959A
- Authority
- CN
- China
- Prior art keywords
- sio
- mno
- icg
- solution
- stirring
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 title claims abstract description 55
- 229910052681 coesite Inorganic materials 0.000 title claims abstract description 53
- 229910052906 cristobalite Inorganic materials 0.000 title claims abstract description 53
- 229910052682 stishovite Inorganic materials 0.000 title claims abstract description 53
- 229910052905 tridymite Inorganic materials 0.000 title claims abstract description 53
- 239000002114 nanocomposite Substances 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Inorganic materials O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims abstract description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000002105 nanoparticle Substances 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 53
- 238000003756 stirring Methods 0.000 claims description 29
- 239000011669 selenium Substances 0.000 claims description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 20
- 238000010438 heat treatment Methods 0.000 claims description 18
- 235000019441 ethanol Nutrition 0.000 claims description 17
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 11
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 11
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 11
- 239000008367 deionised water Substances 0.000 claims description 11
- 229910021641 deionized water Inorganic materials 0.000 claims description 11
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 10
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 10
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 10
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 10
- 239000005642 Oleic acid Substances 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 10
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 10
- 239000012286 potassium permanganate Substances 0.000 claims description 10
- 239000006185 dispersion Substances 0.000 claims description 8
- 239000002243 precursor Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 229920004890 Triton X-100 Polymers 0.000 claims description 6
- 239000013504 Triton X-100 Substances 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- QGLWBTPVKHMVHM-KTKRTIGZSA-N (z)-octadec-9-en-1-amine Chemical compound CCCCCCCC\C=C/CCCCCCCCN QGLWBTPVKHMVHM-KTKRTIGZSA-N 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 239000012046 mixed solvent Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 239000010949 copper Substances 0.000 claims description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 230000000973 chemotherapeutic effect Effects 0.000 claims description 2
- 229960001701 chloroform Drugs 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 239000000463 material Substances 0.000 abstract description 12
- 239000002245 particle Substances 0.000 abstract description 7
- 238000002512 chemotherapy Methods 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 abstract description 3
- 239000003504 photosensitizing agent Substances 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 230000001659 chemokinetic effect Effects 0.000 abstract description 2
- 238000002347 injection Methods 0.000 abstract description 2
- 239000007924 injection Substances 0.000 abstract description 2
- 238000000593 microemulsion method Methods 0.000 abstract description 2
- 239000002159 nanocrystal Substances 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000011248 coating agent Substances 0.000 abstract 1
- 238000000576 coating method Methods 0.000 abstract 1
- 238000010411 cooking Methods 0.000 abstract 1
- 239000012221 photothermal agent Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 35
- 229960004657 indocyanine green Drugs 0.000 description 32
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 32
- 239000007787 solid Substances 0.000 description 11
- 238000011282 treatment Methods 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 10
- 238000002428 photodynamic therapy Methods 0.000 description 9
- 229940079593 drug Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 6
- 229910052711 selenium Inorganic materials 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 5
- 238000011068 loading method Methods 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 4
- 238000007626 photothermal therapy Methods 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 108010087230 Sincalide Proteins 0.000 description 2
- 238000003917 TEM image Methods 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000010609 cell counting kit-8 assay Methods 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000011572 manganese Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000002077 nanosphere Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000001931 thermography Methods 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Images
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to Se @ SiO2@MnO2The preparation method comprises the steps of synthesizing Cu by a thermal injection method2‑xSe nanocrystal coated with SiO by reverse microemulsion method2Synthesis of Se @ SiO2Nanoparticles, and then cooking the material in hot water to form a mediumPore structure, and finally coating manganese dioxide on mesoporous Se @ SiO2Se @ SiO with uniform synthetic particles and good dispersibility on the surfaces of the nanoparticles2@MnO2The nano composite is prepared by utilizing a mesoporous structure to load a photo-thermal reagent, a photosensitizer ICG and an anticancer drug DOX2@MnO2-ICG/DOX nanocomposites. The invention also aims to provide Se @ SiO prepared by the preparation method2@MnO2-ICG nanocomplexes and the clinical use of said compositions as photothermal agents, photosensitizers and chemokinetic agents in combination with chemotherapy.
Description
Technical Field
The invention belongs to the technical field of nano composite particles, and relates to Se @ SiO2@MnO2-ICG nano-composite and preparation method and application thereof.
Background
In recent years, the trend of cancer therapy has shifted from monotherapy to combination therapy. It has been demonstrated that combination therapy by different cancer treatments has a far higher therapeutic effect than monotherapy and can reduce many side effects, such as combining optical therapy (photodynamic and photothermal therapy) with chemotherapy and chemokinetic therapy.
Selenium is an essential trace element for the health and growth of eukaryotic cells, and compared with complex-state selenium or organic selenium (biomolecules containing selenium), selenium nanoparticles (Se nanoparticles) are considered as novel selenium, having many advantages including optimal biocompatibility, simple synthesis, in vivo degradability, and excellent oxidation resistance and anticancer activity, making it possible to be clinically applied as a nano-drug.
Indocyanine green (ICG) is an FDA-approved diagnostic agent in the united states, and ICG has been widely used for PTT as well as PDT due to its NIR optical properties within the optimal absorption window. However, in oxygen-dependent PDT, the consumption of oxygen to generate Reactive Oxygen Species (ROS) leads to a more worsening of the otherwise hypoxic tumor microenvironment, which limits the anti-tumor effects of PDT.
For example, Chinese patent 201810798006.6 discloses an H-MnO2-synthesis and application of ICG composite material.Firstly synthesizing silver nanospheres as a template, then preparing hollow manganese dioxide nanoparticles by using potassium permanganate as a raw material and silver as a reducing agent, and synthesizing H-MnO (manganese dioxide) by using mesopores and electrostatic adsorption loaded ICG (ion-doped silica)2ICG, which is only capable of photothermal/photodynamic therapy, and is not particularly desirable in terms of tumor treatment effect.
Disclosure of Invention
The invention aims to provide Se @ SiO2@MnO2An ICG nano composite, a preparation method and an application thereof, so as to realize the multifunctional treatment of photothermal/photodynamic/chemotherapy/chemodynamic treatment and the like, and the multi-effect synergistic treatment.
The purpose of the invention can be realized by the following technical scheme:
on one hand, the invention provides Se @ SiO2@MnO2-a process for the preparation of an ICG nanocomposite comprising the steps of:
(1) dispersing selenium powder in oleic acid, heating and introducing nitrogen to remove oxygen and moisture, and then heating and stirring to obtain a Se-OA precursor;
(2) dissolving CuCl in mixed solvent of oleylamine and oleic acid, heating and introducing nitrogen to remove oxygen and moisture, heating and stirring, injecting Se-OA precursor to continue reacting to obtain Cu2-xSe, redispersion in organic solvents to give Cu2-xSe solution is used for later use;
(3) uniformly mixing n-hexane, n-hexanol, Triton X-100 and deionized water to be transparent, and then adding Cu2- xSe solution is reacted, then TEOS and ammonia water are dripped, the reaction is continued, ethanol is added for demulsification, excess TEOS is removed by washing, and Se @ SiO is obtained2Nano particles and dispersing in ethanol to obtain Se @ SiO2The solution is ready for use;
(4) taking Se @ SiO2Adding PVP solution into the solution, stirring, heating in water bath and boiling to form porous Se @ SiO2Dispersing in ethanol for later use;
(5) mixing KMnO4The solution is dripped into porous Se @ SiO under the stirring condition2After stirring, the unreacted KMnO was washed off4To obtain Se @ SiO2@MnO2A nanocomposite;
(6) taking Se @ SiO2@MnO2Dispersing the nano composite in ICG dispersion liquid, stirring, centrifuging and washing to obtain a target product Se @ SiO2@MnO2-ICG nanocomplexes.
Further, in the step (1), the mass concentration of the selenium powder dispersed in the oleic acid is 5-10mg/mL, the temperature for heating and stirring is 260-300 ℃, and the time is 20-40 min.
Further, in the step (2), the concentration of CuCl in the mixed solvent is 2-8mg/mL, the volume ratio of oleic acid to oleylamine is 1:1-2, the temperature of heating and stirring is 200-. Preferably, the volume ratio of the Se-OA precursor to the CuCl solution is 1-4: 1.
Further, in the step (2), Cu2-xThe organic solvent used for Se dispersion is one or more selected from N-methyl pyrrolidone, dimethylformamide, dimethyl sulfoxide, acetone, tetrahydrofuran, absolute ethyl alcohol, hexane, methanol, isopropanol, trichloromethane or dichloromethane.
Further, in the step (3), n-hexane, n-hexanol, Triton X-100, deionized water and Cu2-xThe volume ratio of Se solution, TEOS and ammonia water is (140-: 1, wherein, Cu2-xThe concentration of the Se solution is 0.5-50mg/mL, and the concentration of the ammonia water is 25-28%;
adding Cu2-xThe reaction time after Se solution is 2-10min, the dropping speed of TEOS and ammonia water is 1-2 drops/s, and the reaction time after TEOS and ammonia water are added is 12-48 h;
the ratio of ethanol added for demulsification to the total volume of the solution is 1: 20-30.
Further, in the step (4), Se @ SiO2The concentration of the solution is 5-15mg/mL, the concentration of PVP is controlled to be 2-20mg/mL, and the stirring time is 5-40 min; preferably, Se @ SiO2The volume ratio of the solution to the PVP solution can be 1:5 and the like,
the water bath heating temperature is 80-95 deg.C, and the time is 15-40 min.
Further, step (ii)In step (5), porous Se @ SiO2The ethanol solution has a concentration of 2-20mg/mL and KMnO4The concentration of the solution is 0.02-2M, KMnO4Solution and porous Se @ SiO2The volume ratio of the ethanol solution is (2-20): (5-30);
the stirring time is 0.5-6 h.
Further, in the step (6), Se @ SiO2@MnO2The addition ratio of the nano-composite to the ICG dispersion is (2-15) mg: (1-10) mL, wherein the concentration of the ICG dispersion liquid is 1-8 mg/mL;
stirring for 12-50 h;
the centrifugal speed is 4000-10000rpm, and the time is 5-20 min.
On the other hand, the invention also provides Se @ SiO2@MnO2-ICG nanocomposites prepared using the preparation method as described above.
On the other hand, the invention also provides Se @ SiO2@MnO2Application of ICG nanocomposite, Se @ SiO2@MnO2-ICG nanocomposites for the preparation of photothermal, photodynamic, chemotherapeutic or chemo-dynamic therapeutic agents.
The multifunctional composite nano material firstly synthesizes CuSe nano crystal by a thermal injection method, and coats SiO by a reverse microemulsion method2Synthesis of Se @ SiO2The nanoparticles are then boiled in hot water to a mesoporous structure. Using SiO2The reducibility of the residual organic silicon on the surface reduces the added potassium permanganate into manganese dioxide coated porous Se @ SiO2The Se @ SiO with uniform particles and good dispersibility is finally synthesized on the surfaces of the nanoparticles2@MnO2The nano composite is prepared by utilizing a mesoporous structure to load a photo-thermal reagent, a photosensitizer ICG and an anticancer drug DOX2@MnO2-ICG/DOX nanocomposites. Photothermal therapy, photodynamic therapy and chemotherapy are carried out through near-infrared laser irradiation, meanwhile, the tumor microenvironment triggers the chemodynamic therapy, and multiple therapy modes are mutually cooperated, so that the tumor can be completely eliminated, and an ideal treatment effect is achieved.
Compared with the prior art, the invention has the following advantages:
(1) se @ SiO prepared by the method2@MnO2The ICG nano composite has uniform appearance and high photo-thermal conversion efficiency;
(2) se @ SiO prepared by the method2@MnO2ICG nanocomplexes can be MRI imaged, guiding therapy;
(3) se @ SiO prepared by the method2@MnO2the-ICG/DOX nano composite can realize the multifunctional treatment of photothermal/photodynamic/chemotherapy/chemodynamic treatment, and the multi-effect synergistic treatment.
Drawings
FIG. 1 is Se @ SiO solid of example 12@MnO2-low power TEM images of ICG nanocomposites;
FIG. 2 is Se @ SiO solid of example 12@MnO2-high power TEM images of ICG nanocomposites;
FIG. 3 is Se @ SiO solid of example 12@MnO2-ICG nanocomposite particle size distribution profile;
FIG. 4 is Se @ SiO solid of example 12@MnO2-uv absorption profile of ICG nanocomposite;
FIG. 5 is Se @ SiO solid of example 12@MnO2-photothermal performance plots of ICG nanocomposites at different concentrations;
FIG. 6 is Se @ SiO solid of example 12@MnO2-ICG nanocomposite temperature rise and fall profile;
FIG. 7 is Se @ SiO solid of example 12@MnO2-a map of dissolved oxygen performance of ICG nanocomposites;
FIG. 8 is Se @ SiO solid of example 12@MnO2-Se @ SiO of ICG nano composite after medicine loading2@MnO2-ICG/DOX nanocomposite drug release profile;
FIG. 9 is Se @ SiO solid of example 12@MnO2-r of ICG nanocomposite1And r2A relaxation rate;
FIG. 10 is Se @ SiO solid of example 12@MnO2-cell viability map of ICG nanocomplexes;
FIG. 11 shows Se @ SiO solid obtained after drug loading in example 12@MnO2Relative size plot of mouse tumors when ICG/DOX nanocomplexes were treated in vivo.
Detailed Description
The invention is described in detail below with reference to the figures and specific embodiments. The present embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation manner and a specific operation process are given, but the scope of the present invention is not limited to the following embodiments.
In the following examples, unless otherwise specified, the starting materials or processing techniques are all those conventionally available in the art.
Example 1
Se @ SiO2@MnO2-a process for the preparation of an ICG nanocomposite comprising the steps of:
(1) dispersing 43.5mg of selenium powder in 12mL of oleic acid, heating for 5 minutes and introducing nitrogen to remove oxygen and moisture; then, the temperature is increased to 280 ℃ and kept for 30 minutes under vigorous stirring, and a light yellow Se-OA precursor (solution) is prepared for later use; then, CuCl is dissolved in a mixed solvent of 5mL of oleylamine and 5mL of oleic acid, after heating for 5 minutes and introducing nitrogen to remove oxygen and moisture, the mixture is continuously stirred for 10 minutes at 220 ℃; then injecting 12mL of Se-OA precursor into the mixed solution and continuing to react for 5 minutes to generate a dark green solution, namely the obtained Cu2-xWashing with Se and ethanol for three times, and dispersing the obtained product in 10mL of n-hexane to obtain Cu2-xSe solution is used for later use;
(2) mixing 30mL of n-hexane, 3mL of n-hexanol, 3mL of Triton (Triton X-100) and 0.9mL of deionized water uniformly to obtain a transparent mixture, and adding 3mL of Cu prepared in the step (1)2-xSe solution; after 5 minutes, 0.18mL tetraethyl orthosilicate (i.e., TEOS) and 0.18mL ammonia were added dropwise thereto; the reaction was continued for 24 hours, ethanol was added to demulsify the emulsion, and then the emulsion was washed several times with ethanol to remove excess TEOS to obtain Se @ SiO2Dispersing the pure product of the nano particles in ethanol, wherein the concentration of the pure product of the nano particles is 5 mg/mL;
(3) taking 4mL of Se @ SiO2The nano particles are stirred in 20mL of 10mg/mL PVP solution for 30min, boiled in hot water at 95 ℃ to form a porous structure, and then dispersed in an ethanol solution; 10mL of 0.05M KMnO4The solution is added dropwise with 20mL of 5mg/mL porous Se @ SiO under the stirring condition2Was stirred for 4 hours, and then washed three times with deionized water to remove unreacted KMnO4To obtain pure Se @ SiO2@MnO2Dispersing the nano-composite into deionized water, wherein the concentration is 2 mg/mL;
for the Se @ SiO prepared above2@MnO2The nano composite is subjected to various characterizations, and low-power TEM (figure 1) shows that the material has clear particles and good dispersity; high power TEM (FIG. 2) shows Se @ SiO2MnO of surface nanosphere2The successful formation of small particles and the particle size distribution (FIG. 3) also show that the final size of the material is only 68.3nm, indicating that Se @ SiO2@MnO2The nanocomposite can be safely used in vivo.
(4) Taking 8mg Se @ SiO2@MnO2Dispersing the nano particles in 2mL of 1mg/mL ICG solution, stirring for 36h, centrifuging, and washing with deionized water to obtain Se @ SiO2@MnO2-ICG nanocomposite, dispersed in water for later use.
In this example, Se @ SiO2In the process of preparing the pure product of the nano particles, n-hexane, n-hexanol, Triton X-100, deionized water and Cu2-xThe volume ratio of Se solution, TEOS and ammonia water can be (140-200): (10-25): (2-9): (10-30): (0.5-5): 1, the ratio is arbitrarily adjusted to be middle point value or end point value, such as 140:10:10:2:10:0.5:1, 200:25:25:9:30:5:1, and the like.
Example 2
And (3) absorbance test:
se @ SiO obtained in example 12@MnO2The ICG nanocomposites were dispersed in water and the absorption peak at near infrared was measured with UV-Vis spectrophotometer and the successful loading of ICG is shown in FIG. 4.
Example 3
Se@SiO2@MnO2-ICG nanocompositeTesting the photo-thermal performance of the compound:
the Se @ SiO obtained in example 1 is taken2@MnO2Respectively dispersing the ICG nano-composite in deionized water, and putting 0, 50, 100, 200 and 400 mu g/mL solutions in 200 mu L centrifuge tubes with the power density of 1W/cm2And (5) irradiating the laser with the wavelength of 808nm for 5min, and recording the temperature of the solution at different time points. The solution temperature gradually increased with increasing irradiation time and the temperature rise rate was faster with higher concentration, as shown in FIG. 5, which illustrates Se @ SiO2@MnO2The ICG nanocomposite has excellent photothermal conversion properties; 400. mu.g/mL of the solution was placed in a 200. mu.L centrifuge tube at a power density of 1W/cm2And (3) performing laser irradiation with the wavelength of 808nm, and closing the laser to freely cool to room temperature after the temperature is stable (figure 6).
Example 4
Dissolved oxygen test: 1mL of Se @ SiO with different concentrations2@MnO23mL of H were added to each of the ICG nanocomposites (0,60, 120. mu.g/mL)2O2(100. mu.M), the electrodes of the portable dissolved oxygen tester were immediately inserted for testing, and data were collected over 600 seconds. Fig. 7 shows that the material can rapidly generate a large amount of oxygen in a short period of time, and can be used for cooperating with photodynamic therapy and chemotherapy.
Example 5
Drug loading: 24mg of Se @ SiO obtained in example 1 were added2@MnO2Stirring ICG nano particles and 6mL DOX (1mg/mL) together for 36h, centrifuging, washing with deionized water, collecting supernatant, and calculating the drug loading rate by using an ultraviolet spectrophotometer;
and (3) drug release: the obtained Se @ SiO2@MnO2-ICG/DOX NCs were evenly divided into 3 portions, dissolved in PBS solution at pH 5.0, 6.5 and 7.4, followed by evenly dividing each solution again into two portions, with or without 808nm laser irradiation; under the condition of stirring, respectively centrifugally collecting supernatant liquid at preset time for testing concentration by using an ultraviolet spectrophotometer, after laser irradiation of a laser group for 5 minutes, centrifugally testing DOX content by using the ultraviolet spectrophotometer again, continuously adding the centrifugal product into the corresponding PBS solution with the same amount, continuously stirring, repeating the operation steps, and calculating the load efficiency of DOX by using the following formulaRate:
as can be seen from fig. 8, the material can rapidly release DOX under dual regulation of acidity and laser, and can reduce systemic side effects while enhancing the curative effect.
Example 6
MRI performance testing: se @ SiO with different Mn contents2@MnO2The nanoparticles (0, 0.0625, 0.125, 0.25, 0.5, 1mM) were divided into two groups, with or without the addition of 50mM H2O2(ii) a The scanning equipment is ICP-810E (TR/TE 350/0.04 ms). FIG. 9 shows that the MRI imaging signal is obviously improved along with the increase of the Mn ion concentration, and the material has very good MRI performance.
Example 7
Se@SiO2@MnO2-evaluation of biological safety of ICG nanocomplex:
in this example, the CCK-8 kit is used to examine the effect of a549 cell and Beas-2B cell activities on nanoparticles, and the method is as follows: a549 (human non-small cell lung cancer cell) or Beas-2B (human normal lung epithelial cell) and Se @ SiO obtained in example 12@MnO2And (4) detecting the cell survival rate by using a CCK-8 kit after the ICG nano compound is co-cultured. The results show that the material has a cell viability as high as more than 90% even at concentrations as high as 400ug/mL, indicating that the material can be safely used in vivo (fig. 10).
Example 8
In this example, in vivo therapeutic studies on materials were divided into 5 groups of experiments: tumor-bearing mice were randomly divided into 5 groups: (1) control group (No treatment), (2) NIR, (3) DOX, (4) Se @ SiO2@MnO2ICG (i.e.from example 1) + NIR, (5) Se @ SiO2@MnO2ICG/DOX (i.e. drug loaded nanocomplex obtained in example 5) + NIR; the tail vein of each mouse was injected with 200. mu.L (2mg/mL) of the corresponding material, and the groups (2), (4) and (5) were injected with the material and then irradiated with laser5min(808nm，1.0W/cm2) The thermal imaging instrument records temperature change and thermal imaging photos, the weight of the mouse and the size of the tumor are recorded once every two days, and the calculation formula of the size of the tumor is as follows: volume (length and width)2)/2. As can be seen from fig. 11, the complete ablation of the group (5) tumors did not recur after 16 days of treatment, indicating an excellent antitumor effect of the material.
The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. 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 improvements and modifications within the scope of the present invention based on the disclosure of the present invention.
Claims (10)
1. Se @ SiO2@MnO2-a process for the preparation of an ICG nanocomposite, characterized in that it comprises the following steps:
(1) dispersing selenium powder in oleic acid, heating and introducing nitrogen to remove oxygen and moisture, and then heating and stirring to obtain a Se-OA precursor;
(2) dissolving CuCl in mixed solvent of oleylamine and oleic acid, heating and introducing nitrogen to remove oxygen and moisture, heating and stirring, injecting Se-OA precursor to continue reacting to obtain Cu2-xSe, redispersion in organic solvents to give Cu2-xSe solution is used for later use;
(3) uniformly mixing n-hexane, n-hexanol, Triton X-100 and deionized water to be transparent, and then adding Cu2-xSe solution is reacted, then TEOS and ammonia water are dripped, the reaction is continued, ethanol is added for demulsification, excess TEOS is removed by washing, and Se @ SiO is obtained2Nano particles and dispersing in ethanol to obtain Se @ SiO2The solution is ready for use;
(4) taking Se @ SiO2Adding PVP solution into the solution, stirring, heating in water bath and boiling to form porous Se @ SiO2Dispersing in ethanol for later use;
(5) mixing KMnO4The solution is dripped into porous Se @ SiO under the stirring condition2After stirring, the unreacted KMnO was washed off4To obtain Se @ SiO2@MnO2A nanocomposite;
(6) taking Se @ SiO2@MnO2Dispersing the nano composite in ICG dispersion liquid, stirring, centrifuging and washing to obtain a target product Se @ SiO2@MnO2-ICG nanocomplexes.
2. Se @ SiO as claimed in claim 12@MnO2The preparation method of the-ICG nano composite is characterized in that in the step (1), the mass concentration of the selenium powder dispersed in the oleic acid is 5-10mg/mL, the temperature for heating and stirring is 260-300 ℃, and the time is 20-40 min.
3. Se @ SiO as claimed in claim 12@MnO2The preparation method of the-ICG nano composite is characterized in that in the step (2), the concentration of CuCl in the mixed solvent is 2-8mg/mL, the volume ratio of oleic acid to oleylamine is 1:1-2, the temperature for heating and stirring is 200-300 ℃, the stirring time is 20-40min, and the time for continuing the reaction is 3-20min after the Se-OA precursor is added.
4. Se @ SiO as claimed in claim 12@MnO2-a process for the preparation of an ICG nanocomposite, characterized in that in step (2), Cu2-xThe organic solvent used for Se dispersion is one or more selected from N-methyl pyrrolidone, dimethylformamide, dimethyl sulfoxide, acetone, tetrahydrofuran, absolute ethyl alcohol, hexane, methanol, isopropanol, trichloromethane or dichloromethane.
5. Se @ SiO as claimed in claim 12@MnO2The preparation method of the ICG nano composite is characterized in that in the step (3), n-hexane, n-hexanol, Triton X-100, deionized water and Cu2-xThe volume ratio of Se solution, TEOS and ammonia water is (140-200): (10-25): 2-9): 10-30):(0.5-5): 1, wherein, Cu2-xThe concentration of the Se solution is 0.5-50mg/mL, and the concentration of the ammonia water is 25-28%.
Adding Cu2-xThe reaction time after Se solution is 2-10min, the dropping speed of TEOS and ammonia water is 1-2 drops/s, and the reaction time after TEOS and ammonia water are added is 12-48 h;
the ratio of ethanol added for demulsification to the total volume of the solution is 1: 20-30.
6. Se @ SiO as claimed in claim 12@MnO2The preparation method of the-ICG nanocomposite is characterized in that, in the step (4), Se @ SiO2The concentration of the solution is 5-15mg/mL, the concentration of the PVP solution is 2-20mg/mL, and the stirring time is 5-40 min;
the water bath heating temperature is 80-95 deg.C, and the time is 15-40 min.
7. Se @ SiO as claimed in claim 12@MnO2The preparation method of the-ICG nanocomposite is characterized in that, in the step (5), porous Se @ SiO2The ethanol solution has a concentration of 2-20mg/mL and KMnO4The concentration of the solution is 0.02-2M, KMnO4Solution and porous Se @ SiO2The volume ratio of the ethanol solution is (2-20): (5-30);
the stirring time is 0.5-6 h.
8. Se @ SiO as claimed in claim 12@MnO2The preparation method of the-ICG nanocomposite is characterized in that, in the step (6), Se @ SiO2@MnO2The addition ratio of the nano-composite to the ICG dispersion is (2-15) mg: (1-10) mL, wherein the concentration of the ICG dispersion liquid is 1-8 mg/mL;
stirring for 12-50 h;
the centrifugal speed is 4000-10000rpm, and the time is 5-20 min.
9. Se @ SiO2@MnO2-ICG nanocomposites obtained by the preparation process according to any one of claims 1 to 8.
10. The Se @ SiO of claim 92@MnO2-use of an ICG nanocomposite, characterized in that the Se @ SiO2@MnO2-ICG nanocomposites for the preparation of photothermal, photodynamic, chemotherapeutic or chemo-dynamic therapeutic agents.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011268834.2A CN112656959A (en) | 2020-11-13 | 2020-11-13 | Se @ SiO2@MnO2-ICG nano composite and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011268834.2A CN112656959A (en) | 2020-11-13 | 2020-11-13 | Se @ SiO2@MnO2-ICG nano composite and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112656959A true CN112656959A (en) | 2021-04-16 |
Family
ID=75403345
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011268834.2A Pending CN112656959A (en) | 2020-11-13 | 2020-11-13 | Se @ SiO2@MnO2-ICG nano composite and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112656959A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105079027A (en) * | 2015-08-13 | 2015-11-25 | 上海工程技术大学 | Porous Se-SiO2 nanoparticle as well as preparation method and application thereof |
| CN108969766A (en) * | 2018-07-19 | 2018-12-11 | 深圳华创生物医药科技有限公司 | Photosensitized composite material and preparation method with tumor microenvironment response oxygenation performance |
| CN110623940A (en) * | 2019-09-09 | 2019-12-31 | 上海工程技术大学 | Selenium/silicon dioxide/gold nano composite particle and preparation method and application thereof |
| CN111228300A (en) * | 2019-12-30 | 2020-06-05 | 清华大学 | Preparation method and application of manganese dioxide-coated polydopamine-selenium nanoenzyme |
-
2020
- 2020-11-13 CN CN202011268834.2A patent/CN112656959A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105079027A (en) * | 2015-08-13 | 2015-11-25 | 上海工程技术大学 | Porous Se-SiO2 nanoparticle as well as preparation method and application thereof |
| CN108969766A (en) * | 2018-07-19 | 2018-12-11 | 深圳华创生物医药科技有限公司 | Photosensitized composite material and preparation method with tumor microenvironment response oxygenation performance |
| CN110623940A (en) * | 2019-09-09 | 2019-12-31 | 上海工程技术大学 | Selenium/silicon dioxide/gold nano composite particle and preparation method and application thereof |
| CN111228300A (en) * | 2019-12-30 | 2020-06-05 | 清华大学 | Preparation method and application of manganese dioxide-coated polydopamine-selenium nanoenzyme |
Non-Patent Citations (3)
| Title |
|---|
| MINYI ZHANG ET AL.: "Tumor environment responsive degradable CuS@mSiO2@MnO2/DOX for MRI guided synergistic chemo-photothermal therapy and chemodynamic therapy", 《CHEMICAL ENGINEERING JOURNAL》 * |
| WENYAN KONG ET AL.: "Se@SiO2@Au-PEG/DOX NCs as a multifunctional theranostic agent efficiently protect normal cells from oxidative damage during photothermal therapy", 《DALTON TRANS》 * |
| XIJIAN LIU ET AL.: "Selenium nanocomposites as multifunctional nanoplatform for imaging guiding synergistic chemo-photothermal therapy", 《COLLOIDS AND SURFACES B: BIOINTERFACES》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107753946B (en) | Aptamer-modified targeted drug-loaded nanoparticle and preparation method and application thereof | |
| CN108159422B (en) | Self-assembly drug delivery system and preparation method of composite preparation thereof | |
| CN108675280B (en) | Phenothiazine derivative fluorescent carbon dot and preparation method and application thereof | |
| CN108888767B (en) | Nano composite material, preparation method and application thereof | |
| US20110196285A1 (en) | Hollow Mesoporous Silica Sphere Coated with Gold and Preparation Method Thereof and Use in Cancer Therapy | |
| Youssef et al. | Titania and silica nanoparticles coupled to Chlorin e6 for anti-cancer photodynamic therapy | |
| CN105412948B (en) | It is multi-functional to contain hollow mesoporous prussian blue nano diagnosis and treatment agent of gadolinium and its preparation method and application | |
| CN103961705B (en) | The preparation of the hollow copper sulfide/poly-dopamine complex of modified with folic acid and application thereof | |
| CN109010850B (en) | Preparation method and application of curcumin-loaded glucan-modified gadolinium-doped hollow mesoporous silica nanomaterial | |
| Cai et al. | Polypyrrole-coated UCNPs@ mSiO 2@ ZnO nanocomposite for combined photodynamic and photothermal therapy | |
| CN104784707B (en) | A kind of hollow nuclear shell structure nano diagnosis and treatment agent of cancer target and its preparation method and application | |
| CN111569073A (en) | Photosensitizer-loaded mesoporous Prussian blue-manganese nanoparticles and preparation method thereof | |
| CN105903015A (en) | Multifunctional thermosensitive agarose hydrogel and preparation method and application thereof | |
| CN108904471B (en) | Nano drug carrier Au/MnO2And preparation method and application thereof | |
| CN108969766B (en) | Photosensitive composite material with tumor microenvironment response oxygenation performance and preparation method thereof | |
| Boudon et al. | Magneto-optical nanomaterials: a SPIO–phthalocyanine scaffold built step-by-step towards bimodal imaging | |
| CN103463639B (en) | A kind of controlled release durg delivery system and preparation method thereof | |
| CN110623940A (en) | Selenium/silicon dioxide/gold nano composite particle and preparation method and application thereof | |
| Li et al. | Targeted pH/redox dual-responsive nanoparticles for cancer chemotherapy combined with photodynamic/photothermal therapy | |
| CN112336858B (en) | Bismuth-manganese-based composite particle and preparation method and application thereof | |
| CN114306636A (en) | Photoresponse silicon dioxide material and preparation method and application thereof | |
| Jia et al. | Near-infrared upconversion photosensitizer enabling photodynamic production and in situ dynamic monitoring of hydroxyl radical in live mice | |
| CN112656959A (en) | Se @ SiO2@MnO2-ICG nano composite and preparation method and application thereof | |
| CN112023041A (en) | Selenium/silicon dioxide/bismuth nano composite material and preparation and application thereof | |
| CN112972423A (en) | Cascade reaction-based nano enzyme and chemotherapeutic drug co-loaded bionic nano drug carrier and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210416 |