CN108066765A - Mitochondrially targeted silicon Nano medication delivery vector prepares and carrier application - Google Patents
Mitochondrially targeted silicon Nano medication delivery vector prepares and carrier application Download PDFInfo
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
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Abstract
The invention discloses a kind of preparation methods of Mitochondrially targeted silicon Nano medication delivery vector, be intended to provide a kind of preparation method it is simple, it is of low cost, have industrialized production future silicon Nano medication delivery vector prepare new process and new method, technical points be：Silane-water solution is mutually added to be led in the oil phase that X 100, alkane, alcohols and pore-foaming agent form by Qula under agitation as water forms water-in-oil inverse microemulsion, ethyl orthosilicate (TEOS) and ammonium hydroxide triggering polymerisation are added in after a period of stabilisation, acetone terminates reaction and obtains silicon nanoparticle, silicon nanoparticle is added in acetic acid solution again and removes pore-foaming agent to get nanometer grain.The silicon nanoparticle of preparation has hollow or solid construction, and grain size is 20 100nm, and shell mesopore diameter is 1 10nm.The nanoparticle also have the function of it is Mitochondrially targeted can be gathered spontaneously in mitochondria, new platform can be provided for the treatment of mitochondria class disease.
Description
Technical field
This technology is related to field of biological pharmacy, and particularly a kind of silicon Nano medication for Mitochondrially targeted treatment, which delivers, to be carried
The preparation method of body, silicon nanoparticle grain size prepared by this method is smaller, can be gathered spontaneously in mitochondria.
Background technology
As the energy plants of human body, mitochondria dysfunction can cause a variety of diseases, such as Alzheimer's disease (text
Offer 1：Nunomura A,et al.J Neuropathol Exp Neurol 2001；60:759-767；Document 2：Wang X,et
al.Biochimica et biophysica acta 2014；1842:1240-1247), Parkinson's disease (document 3：
S,et al.Biological Chemistry 1999；380:865-870), obesity (document 4：Blaikie FH,et
al.Bioscience reports 2006；26:231-243；Document 5：Martínez JA.et al.Journal of
Physiology&Biochemistry 2006；62:303-306), type-2 diabetes mellitus (document 6：Lowell BB,et
al.Science 2005；307:384-7), more property hardening (documents 7：Witte ME,et al.Trends in molecular
medicine 2014；20:179-187) and cancer (document 8：Neuzil J,et al.Journal of
bioenergetics and biomembranes 2007；39:65-72；Document 9：Armstrong JS.et al.British
journal of pharmacology 2006；147:239-248).For these diseases, there are many drugs in clinic
Extensive use is such as used to treat the curcumin (document 10 of Alzheimer's disease:Ono K,et al.Journal of
Neuroscience Research 2004；75:742-750), for the chemotherapeutic drug Paclitaxel, camptothecine, chlorine for the treatment of cancer
Ni Daming (documents 11：Floridi A,et al.Journal of the National Cancer Institute 1981；
66:497-499), for treating the anti-oxidant phosphorylation uncouplers dinitrophenol dinitrophenolate (document 12 of obesity：Harper JA,et
al.Obesity Reviews 2001；2:255-265) etc..But clinical treatment outcome shows that these drugs cannot enter line grain
In vivo, it is therapeutically effective concentration.Therefore how the key issue of mitochondria dysfunction treatment at present is by medicine
Object is safely and efficiently delivered in mitochondria and plays therapeutic effect.(document 13：Hockenbery DM.Environmental&
Molecular Mutagenesis 2010；51:476–489).To solve the problems, such as this, researcher is attempted using active transport
With two kinds of strategies of passive transport drug targeting is made to enter mitochondria, the former is special by drug delivery vehicle and mitochondria specific site
Opposite sex interaction realizes that cross-film is transported, such as gramicidin S peptide；The latter realizes that film leads to by changing the physicochemical property of mitochondrial membrane
The raising of permeability energy, such as potential, hydrophilic and hydrophobic.At present, the drug delivery system that can successfully target mitochondria mainly has
It is coupled Mitochondrially targeted peptide medicine delivery system (document 14：Li J,et al.Biochemical&Biophysical
Research Communications,2011,404:349-356), liposomal drug delivery system (document 15：Szeto
HH.Aaps Journal,2006,8:535-546), it is coupled lipophilic cation triphenylphosphine drug delivery system (document 16：
Smith RAJ,et al.Proceedings of the National Academy of Sciences,2003,100:
5407-5412；Document 17：Marrache S,et al.Proceedings of the National Academy of
Sciences,2012,109:16288-16293) etc..But coupling TPP or targeting peptides need to carry out complicated chemical reaction,
And the organic solvent introduced in reaction process is difficult to eliminate completely, into may cause the devices such as nervous system, liver kidney in vivo
The damage of official.And liposome structure stability is poor, easily removes (document by quick with the protein-interacting in serum
18：Chonn A,et al.Advanced Drug Delivery Reviews,1998,30:73-83).Nano-medicament carrier can
With well solve above-mentioned delivery system there are the problem of, study the main organic/inorganic nano grain of more nano-medicament carrier at present
(metal nanoparticle, nanometer pharmaceutical carrier, carbon nanotubes pharmaceutical carrier), high molecular polymer (artificial synthesized amphiphilic
Property esters macromolecule, artificial synthesized peptide amphiphile family macromolecule, natural polysaccharide modified high-molecular), dendritic polymer, polymerization
Object-drug coupling body (polymer P GA, HPMA, PEG) etc..Silicon nanoparticle is due to having than table in numerous administration nano-drug administration systems
Area is big, chemically and thermally have good stability, the advantages that medicament storage and sustained release performance are excellent causes the very big interest of researcher,
It is widely used in (document 19 in drug delivery, image probe and biological diagnosis and treatment：Rosenholm JM,et
al.Nanomedicine,2012,7:111-120；Document 20：Ambika B,et al.Journal of the American
Chemical Society,2013,135:7815-7818).Silicon nano-delivery system since 1992 by since reporting for the first time just
It being widely used in drug controlled release, good biocompatibility makes it have good distribution and discharge capacity in vivo,
The absorption and loading that big specific surface area and pore volume is drug in duct provide sufficient space, unique meso-hole structure
And controllable aperture can realize better medicine sustained and controlled release, the substantial amounts of active group in surface can carry out functional modification realization
The targeted delivery of drug, stimuli responsive type release, while also can be by being coupled modified magnetic iron oxide, medical image molecule, light
Quick dose is waited the integration for realizing magnetic guiding, drug delivery, Multimodal medical image and a variety of therapeutic modalities.Silicon Nano medication delivers
It is bigger (generally higher than there are grain size although system has broad application prospects in terms of targeted therapy and slow controlled release
The problem of 200nm) being not easy by cellular uptake.It is well known that the grain size of drug delivery system directly affects its following in blood
Ring time and cellular uptake mechanism, submicron particles of the grain size more than 500nm are rapidly by capillary network after intravenous injection administration
It absorbs or by intrapulmonary capillary mechanical retention, grain size is more than the particle of 100nm easily by the reticuloendothelial system of liver and spleen
It swallows and removes, particle of the grain size in 50-100nm can enter hepatic parenchymal cells, and particle of the grain size less than 50nm can then lead to
It crosses lymphatic system and reticuloendothelial system penetrates into tumor blood vessels and enters tumour cell.Therefore, if wanting to make silicon nanometer medicine
Object delivery system enters after human body not to be removed quickly by body, and realizes tumour passive target, then is needed through certain method
Make silicon Nano medication delivery system that there is smaller grain size.
For the problems of Mitochondrially targeted drug delivery system, with reference to silicon nanoparticle in delivery process
Advantage, we have developed a kind of preparation sides for the small particle silicon administration nano-drug administration system that can encapsulate antitumor drug and diagnostic reagent
Method, the silicon administration nano-drug administration system have the function of Mitochondrially targeted, and the treatment for mitochondria dysfunction class disease provides new platform.
The content of the invention
For Mitochondrially targeted drug delivery system there are the problem of, the present invention provides one kind have Mitochondrially targeted work(
The small particle silicon nanoparticle preparation method of energy, and construct the Nano medication with target function based on the nanoparticle and carry
Body.
To achieve the above object, technical scheme is as follows：It is prepared using reverse microemulsion method with Mitochondrially targeted
The small particle silicon nanoparticle of function, and realize that Intramitochondrial targeting is assembled using the nanoparticle as pharmaceutical carrier, it is characterised in that
It comprises the following steps that：
(1) silane is dissolved in water and prepares microemulsion water phase, and triton x-100, alkane, alcohols and pore-foaming agent are mixed with micro emulsion
Liquid oil phase；(2) oil phase is added in reactor, is mutually slowly added into oil phase water forms water-in-oil inverse under agitation
Microemulsion system stirs a period of time microemulsion；
(3) ethyl orthosilicate (TEOS) and ammonium hydroxide triggering polymerisation are added in after microemulsion is stablized, is added in after reaction
Acetone terminates reaction, forms silicon nanoparticle；
(4) silicon nanoparticle is cleaned 2-5 times successively with absolute ethyl alcohol and deionized water, removes unreacted monomer and solvent；
(5) nanoparticle cleaned up is added in acetic acid solution, and the pore dosage form in nanoparticle is removed under stirring condition
Into mesoporous, deionized water cleans 2-5 times to get nanometer grain；
(6) silicon nanoparticle loads drug using infusion method, and silicon nanoparticle is placed in drug solution, 4 DEG C of standing 48h；Centrifugation
It collects nanoparticle to be cleaned 4-10 times with the PBS solution of pH7.4, washes away the drug of unloaded to get medicine silicon nanoparticle is carried.
Silicon nanoparticle prepared by above-mentioned technique is hollow or solid, grain size 20-100nm, and shell mesopore diameter is 1-
10nm；
Silicon nanoparticle prepared by above-mentioned technique has the function of Mitochondrially targeted, can be gathered spontaneously in mitochondria；
Silane in above-mentioned steps (1) includes but not limited to aminopropyl triethoxysilane (APS), 3- (glycidyl)
Propyl trimethoxy silicane (GPTMS), 3- (methacryloxy) propyl trimethoxy silicane (MEMO), dichloro-dimethyl silicon
Alkane (DMCS), trim,ethylchlorosilane (TMCS), hexamethyldisilazane (HMDS) etc.；Alkane includes but not limited to n-hexane, first
Alkane, propane, butane, hexane etc.；Alcohols includes but not limited to ethyl alcohol, propyl alcohol, isopropanol, n-butanol, isobutanol, n-hexyl alcohol, just
Octanol, n-heptanol etc.；Pore-foaming agent includes but not limited to cetyl trimethylammonium bromide (CTAB), dodecyl dimethyl benzyl
Ammonium chloride (DDBAC), didecyl Dimethy ammonium chloride (DDAC), tetrabutylammonium bromide (TBAB), CaCO3、Mg CO3Deng.
The concentration of silane is 0.1-1% (w/v) in water phase in above-mentioned steps (1)；Distribution ratio is grouped in oil phase is：Pore-foaming agent
0.001-0.1% (w/v), alkane 40-80% (w/v), Triton X-100 10-20% (w/v), alcohols 10-20% (w/v).
Mixing speed in above-mentioned steps (2) is 200-1000rpm；Stirring stabilization time is 20-120min.
The addition of ethyl orthosilicate (TEOS) is 0.1-1% in above-mentioned steps (3), adds in mass concentration (w/v, g/ml)
For 28% ammonium hydroxide, and the final concentration of 0.1-1% of addition (w/v, g/ml) for adjusting ammonium hydroxide；Reaction time is 12-48h, reaction
Temperature is 20-40 DEG C；Acetone addition is the 20-50% of reaction system total volume.
Acetic acid additive amount is the 50-200% of nanoparticle volume in above-mentioned steps (5)；Mixing speed is 200-1000rpm,
Reaction time is 1-8h；Reaction temperature is 20-40 DEG C；
The drug loaded in above-mentioned steps (6) includes but not limited to adriamycin, taxol, camptothecine, Lonidamine, 5- fluorine
The clinical treatments drug such as uracil, oxaliplatin, docetaxel, gemcitabine, capecitabine, vinorelbine, curcumin, Yin
Diindyl cyanines are green to wait photo-thermal therapies drug and near-infrared contrast agent, Fe2+、Mn2+、Gd2+Wait magnetic resonance imaging contrasts.
The invention has the advantages that
(1) hollow nanometer grain is prepared using reverse microemulsion method, its preparation method is simple, micro- by water-in-oil inverse
Newborn one step of system is i.e. available, and be easy to purify, without chemical modification, do not introduce other organic solvents etc..
(2) compared with other mesoporous silicon carriers, hollow nanometer grain grain size is smaller, and has hollow structure, greatly
Specific surface area is added greatly, makes it have higher drug delivered payload capability.
(3) hollow nanometer grain has the ability assembled in cell mitochondrial in itself, while has slow-release capability,
The long-term treatment to mitochondria dysfunction class disease can be achieved.
Description of the drawings
Fig. 1 is the TEM image and particle diameter distribution of hollow nanometer grain.
Fig. 2 is adriamycin and carries adriamycin silicon nanoparticle in positioning intracellular Hela, bar=30 μm..
Fig. 3 is the TEM image and particle diameter distribution of the hollow silicon nanoparticle containing SPIO.
Fig. 4 is the TEM image and particle diameter distribution of the hollow silicon nanoparticle containing Gd (DOTA).
Specific embodiment
The present invention is described in detail with reference to specific embodiment.Following embodiment will be helpful to the technology of this field
Personnel further understand the present invention, but do not form any limitation of the invention.Anyone is within the scope of the invention as claimed
Any type of modification made, still within the claims in the present invention protection domain.Embodiment 1
(1) 20 μ L aminopropyl triethoxysilanes (APS), which are dissolved in 4.4mL deionized waters, prepares microemulsion water phase, 15mg
Cetyl trimethylammonium bromide (CTAB), 72.6mL hexamethylenes, the mixing of 17.88g Triton X-100 and 17.6mL n-octyl alcohol
Prepare microemulsion oil phase；
(2) it is 400rpm that oil phase, which is added to adjustment speed of agitator in reactor, and water is mutually slowly added into shape in oil phase
Into water-in-oil inverse microemulsion system, 30min microemulsions are stirred；
(3) microemulsion adds in 900 μ L ethyl orthosilicates (TEOS) and 800 μ L ammonium hydroxide triggering polymerisation, reaction after stablizing
After add in 40mL acetone and terminate reaction, form silicon nanoparticle；
(4) silicon nanoparticle is cleaned three times successively with absolute ethyl alcohol and deionized water, removes unreacted monomer and solvent；
(5) nanoparticle cleaned up is added in isometric acetic acid solution, is reacted under conditions of 400rpm rotating speeds
1h removal nanoparticle in pore-foaming agent formed it is mesoporous, deionized water clean three times to get nanometer grain；
(6) silicon nanoparticle loads drug using infusion method, and silicon nanoparticle is placed in the Doxorubicin solution that concentration is 5mg/ml,
4 DEG C of standing 48h；Nanoparticle is collected by centrifugation to be cleaned five times with the PBS solution of pH7.4, washes away the adriamycin of unloaded to get loading
The silicon nanoparticle of adriamycin.
Silicon nanoparticle prepared by above-mentioned technique is hollow nanoparticle, and average grain diameter is 31.67 ± 3.14nm, nanoparticle center
Bore dia is 11.24 ± nm (Fig. 1), and surface area and pore volume are respectively 235.43m2/ g and 0.45cm3/ g, shell wall surface are mesoporous
A diameter of 7.84nm, porosity 32.55%, and silicon nanoparticle have the ability (Fig. 2) that spontaneous targeting gathers mitochondria.
Its process is：The cell density for adjusting human cervical carcinoma cell Hela suspensions is 5 × 104/ mL, take 1mL cell suspension inoculations to swash
In the burnt capsule of light copolymerization.Supernatant discarding after incubation is paved with ware bottom to cell adds in the doxorubicin hydrochloride (DOX) containing isoconcentration, carries
The culture medium of medicine silicon nanoparticle (Si-DOX), 4h is incubated with cell altogether.Culture medium is discarded, adds in 1mL 100nM's
Mitotracker Deep Red probe solutions are incubated 30min.Supernatant discarding, cell is with after PBS cleaning 3 times, laser co-focusing
The positioning scenarios of microscopic system observation DOX, Si-DOX in the cell.Wherein, DOX and Mitotracker Deep Red distinguish
It is excited with 488nm and 633nm, corresponding transmitted wave is 520-600nm and 650-700nm.The results show is for free Ah mould
Element is mainly gathered in nucleus, the Pearson's coefficient (Pearson ' s Coefficient) of the two for 0.126 ±
0.032.And adriamycin does not enter nucleus, but be uniformly dispersed in cytoplasm, with Mitotracker discrete areas phases
Together, the Pearson's coefficient of the two is 0.762 ± 0.065, shows that adriamycin is largely assembled in cell mitochondrial.
Embodiment 2
1) 30 μ L aminopropyl triethoxysilanes (APS), which are dissolved in 5.3mL deionized waters, prepares microemulsion water phase, and 20mg is double
Ten alkyl dimethyl ammonium chlorides (DDAC), 68.5mL hexamethylenes, 16.94g Triton X-100 and 27.6mL n-heptanol mixing system
Standby microemulsion oil phase；
(2) it is 300rpm that oil phase, which is added to adjustment speed of agitator in reactor, and water is mutually slowly added into shape in oil phase
Into water-in-oil inverse microemulsion system, 30min microemulsions are stirred, then add in Fe3O4Nanoparticle continues to stir 30min；
(3) 1.5mL ethyl orthosilicates (TEOS) and 1.2mL ammonium hydroxide triggering polymerisation, reaction are added in after microemulsion is stablized
After add in 40mL acetone and terminate reaction, form silicon nanoparticle；
(4) silicon nanoparticle is cleaned three times successively with absolute ethyl alcohol and deionized water, removes unreacted monomer and solvent；
(5) nanoparticle cleaned up is added in isometric acetic acid solution, is reacted under conditions of 400rpm rotating speeds
1h removal nanoparticle in pore-foaming agent formed it is mesoporous, deionized water clean three times, obtain with Fe3O4It is received for the silicon containing SPIO of core
The grain of rice.
Silicon nanoparticle prepared by above-mentioned technique is hollow nanoparticle, and average grain diameter is 30.10 ± 2.18nm, nanoparticle center
Bore dia be 7.64 ± 1.36nm (Fig. 3), shell wall surface mesopore diameter be 6.89nm, porosity 29.14%.
Embodiment 3
(1) c-terminus in Pen Suan Portugals amine (DOTA) introduces alkyl protection, forms Tb (DOTA), Tb (DOTA) and aminopropyl
Triethoxysilane (APS) polymerization forms APS-Tb (DOTA), and 25 μ L aminopropyl triethoxysilanes APS-Tb (DOTA) are dissolved in
Prepare microemulsion water phase in 4.7mL deionized waters, 20mg cetyl trimethylammonium bromides (CTAB), 74.3mL n-hexanes,
15.96g Triton X-100 and 19.7mL n-octyl alcohols are mixed with microemulsion oil phase；
(2) it is 400rpm that oil phase, which is added to adjustment speed of agitator in reactor, and water is mutually slowly added into shape in oil phase
Into water-in-oil inverse microemulsion system, 30min microemulsions are stirred；
(3) 1.2mL ethyl orthosilicates (TEOS) and 0.9mL ammonium hydroxide triggering polymerisation, reaction are added in after microemulsion is stablized
After add in 50mL acetone and terminate reaction, form silicon nanoparticle；
(4) silicon nanoparticle is cleaned three times successively with absolute ethyl alcohol and deionized water, removes unreacted monomer and solvent；
(5) silicon nanoparticle is added to volume ratio as 1:1 CH2Cl2In/TFA solution, 2h is stirred under the conditions of 400rpm, makes Tb
(DOTA) slough blocking group and form DOTA；
(6) nanoparticle cleaned up is added in isometric acetic acid solution, is reacted under conditions of 400rpm rotating speeds
1h removal nanoparticle in pore-foaming agent formed it is mesoporous, deionized water clean three times to get nanometer grain；
(7) nanoparticle is dispersed in the gadolinium acetate aqueous solution of pH 5.5,90 DEG C of reflux 2h make Gd and the complete chelas of DOTA
It closes, obtains the hollow nanometer grain containing Gd (DOTA).
Silicon nanoparticle prepared by above-mentioned technique is hollow nanoparticle, and average grain diameter is 38.03 ± 3.77nm, nanoparticle center
Bore dia is 7.01 ± 1.40nm, and shell wall surface mesopore diameter is 8.57nm, and porosity is 27.39% (Fig. 4).
Claims (9)
1. a kind of preparation method of Mitochondrially targeted silicon Nano medication delivery vector, which is characterized in that comprise the following steps that：
(1) silane is dissolved in water and prepares microemulsion water phase, and triton x-100, alkane, alcohols and pore-foaming agent are mixed with microemulsion oil
Phase；(2) oil phase is added in reactor, and water is added to formation water-in-oil inverse micro emulsion body in oil phase under agitation
Microemulsion stirs in system；
(3) ethyl orthosilicate (TEOS) and ammonium hydroxide triggering polymerisation are added in after microemulsion is stablized, adds in acetone after reaction
Reaction is terminated, forms silicon nanoparticle；
(4) silicon nanoparticle is cleaned 2-5 times successively with absolute ethyl alcohol and deionized water, removes unreacted monomer and solvent；
(5) nanoparticle cleaned up is added in acetic acid solution, and the pore-foaming agent removed under stirring condition in nanoparticle forms Jie
Hole, deionized water clean 2-5 times to get nanometer grain.
(6) silicon nanoparticle loads drug using infusion method, and silicon nanoparticle is placed in drug solution, 4 DEG C of standing 48h；It is collected by centrifugation
Nanoparticle is cleaned 4-10 times with the PBS solution of pH7.4, washes away the drug of unloaded to get medicine silicon nanoparticle is carried.
2. preparation method according to claim 1, it is characterized in that, the silane in the step (1) includes but not limited to ammonia
Propyl-triethoxysilicane (APS), 3- (glycidyl) propyl trimethoxy silicane (GPTMS), 3- (methacryloxypropyls
Base) propyl trimethoxy silicane (MEMO), dichlorodimethylsilane (DMCS), trim,ethylchlorosilane (TMCS), two silicon of hexamethyl
One or two or more kinds of alkane in ammonia alkane (HMDS) etc. include but not limited in n-hexane, methane, propane, butane, hexane etc.
One or two or more kinds；Alcohols includes but not limited to ethyl alcohol, propyl alcohol, isopropanol, n-butanol, isobutanol, n-hexyl alcohol, just pungent
One or two or more kinds in alcohol, n-heptanol etc.；Pore-foaming agent includes but not limited to cetyl trimethylammonium bromide (CTAB), ten
Dialkyl dimethyl benzyl ammonium chloride (DDBAC), didecyl Dimethy ammonium chloride (DDAC), tetrabutylammonium bromide (TBAB),
CaCO3、MgCO3One or two or more kinds in；
The concentration of silane is 0.1-1% (w/v, g/ml) in water phase in the step (1)；Distribution ratio is grouped in oil phase is：Pore
Agent 0.001-0.1% (w/v, g/ml), alkane 59.999-79.999% (w/v, g/ml), Triton X-100 10-20% (w/
V, g/ml), alcohols 10-20% (w/v, g/ml).
3. preparation method according to claim 1, it is characterized in that, the volume ratio of water phase and oil phase in the step (2)
For 1:5-40, mixing speed 200-2000rpm；Mixing time is 20-120min；Ethyl orthosilicate in the step (3)
(TEOS) the final concentration of 0.1-1% of addition (w/v, g/ml) adds in mass concentration (w/v, g/ml) and is 28% ammonium hydroxide, and adjusts
The final concentration of 0.1-1% of addition (w/v, g/ml) of whole ammonium hydroxide；Reaction time is 12-48h, and reaction temperature is 20-40 DEG C；Acetone
Addition is the 20-50% of reaction system total volume.
4. preparation method according to claim 1, it is characterized in that, acetic acid concentration is 10%-100% in the step (5)
(w/v, g/ml), the additive amount in the acetic acid late into the night are the 50-200% of nanoparticle volume；Mixing speed is 200-1000rpm, reaction
Time is 1-8h；Reaction temperature is 20-40 DEG C.
5. a kind of silicon nano-carrier that any preparation methods of claim 1-4 obtain.
6. silicon nano-carrier according to claim 5, it is characterized in that, prepared silicon nanoparticle has hollow structure or reality
Core structure；Hollow structure：Grain size is 20-100nm, a diameter of 5-20nm of center cavity, and mesopore diameter is 1- on shell wall surface
10nm, porosity 20-40%；Solid construction grain size is 20-100nm, mesopore diameter 1-10nm, porosity 20-40%.
7. a kind of application of silicon nano-carrier described in claim 5 or 6, it is characterized in that, silicon nanoparticle has Mitochondrially targeted
Function can be gathered spontaneously in human or animal's cell mitochondrial.
8. the application of silicon nano-carrier according to claim 7, it is characterized in that, silicon nanoparticle loads medicine using infusion method
Object, silicon nanoparticle are placed in drug solution, 0-4 DEG C of standing 36-72h；Nanoparticle is collected by centrifugation and cleans 4-10 with PBS buffer solutions
It is secondary, the drug of unloaded is washed away to get medicine silicon nanoparticle is carried.
9. the application of silicon nano-carrier according to claim 7, it is characterized in that, the drug includes but not limited to Ah mould
Element, taxol, camptothecine, Lonidamine, 5 FU 5 fluorouracil, oxaliplatin, docetaxel, gemcitabine, capecitabine, different length
The near-infrareds contrast agent such as one or two or more kinds or indocyanine green in the clinical treatments drug such as spring flower alkali, curcumin contain
Fe2+、Mn2+Or Gd2+Magnetic resonance imaging contrast.
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