CN102416178A - Water-soluble non-aggregated alkoxy-substituted phthalocyanine-silica nanometer particle - Google Patents

Water-soluble non-aggregated alkoxy-substituted phthalocyanine-silica nanometer particle Download PDF

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CN102416178A
CN102416178A CN2011103735256A CN201110373525A CN102416178A CN 102416178 A CN102416178 A CN 102416178A CN 2011103735256 A CN2011103735256 A CN 2011103735256A CN 201110373525 A CN201110373525 A CN 201110373525A CN 102416178 A CN102416178 A CN 102416178A
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phthalocyanine
particle
water
substituted phthalocyanine
aggregated
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CN102416178B (en
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王建
江舟
胡艳丽
韩璐
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Fuzhou University
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Fuzhou University
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Abstract

The invention provides a water-soluble non-aggregated alkoxy-substituted phthalocyanine-silica nanometer particle and a preparation method thereof. The water-soluble non-aggregated alkoxy-substituted phthalocyanine-silica nanometer particle is a photosensitizer nanometer particle for photodynamic therapy (PDT) and photodynamic diagnosis (PDD). Common phthalocyanine has the characteristics of poor water solubility and easiness of aggregation and thus use of the common phthalocyanine in the PDT and the PDD is influenced by the characteristics. The water-soluble non-aggregated alkoxy-substituted phthalocyanine-silica nanometer particle is characterized in that non-aggregated alkoxy-substituted phthalocyanine (MPc(OR)4) is coated with a SiO2 nanometer particle and the SiO2 nanometer particle with the non-aggregated alkoxy-substituted phthalocyanine (MPc(OR)4) is prepared into the water-soluble non-aggregated alkoxy-substituted phthalocyanine-silica (MPc(OR)4-SiO2) nanometer particle. The water-soluble non-aggregated alkoxy-substituted phthalocyanine-silica nanometer particle partly solves the problem of the common phthalocyanine, and is conducive to development of phthalocyanine as a photodynamic diagnosis and treatment reagent.

Description

The non-gathering alkoxyl of water solublity substituted phthalocyanine-nano SiO 2 particle
Technical field
The invention belongs to the PDT field, relate to a kind of photosensitizer that is used for photodynamic therapy, the method for preparing of the non-gathering alkoxyl of a kind of water solublity substituted phthalocyanine-nano SiO 2 particle of more specifically saying so.
Background technology
Photodynamic therapy (PDT) is a kind of method that can be used for treating various tumors, cardiovascular, skin and ophthalmic diseases; Light power diagnosis (PDD) is based on fluorescence, utilizes photodynamic reaction to carry out the technology of medical diagnosis on disease.The principle of the photodynamic therapy of cancer is: photosensitizer (PS) but behind the administration certain hour relative rich combine in tumor tissues; This moment is with the visible light or near infrared light (NIR) the irradiation tumor tissues of suitable wavelength; The photosensitizer molecule of enrichment is activated in the tumor tissues; And the oxygen molecule around energy conduction given, cause reactive oxygen species (ROS), such as singlet oxygen ( 1O 2) or the generation of free radical.Life-span of ROS is short, and it can be confined to very little scope to the disorganization effect, so PDT can destroy illing tissue effectively, selectively, and does not damage surrounding health tissue.
Phthalocyanines photosensitizer stable in properties, and absorption maximum is positioned at the high red light district of tissue transmitance, become the research focus of PDT photosensitizer, also is expected to be used for the PDD technology.But, because the poorly water-soluble of phthalocyanine own is difficult for administration, the easy gathering causes that the degradation characteristics have influenced its application in clinical greatly under fluorescent quenching and the ROS productive rate.
In the nano-medicament carrier field, nano SiO 2 particle is the research object.Nano SiO 2 particle is a kind of nontoxic, tasteless, free of contamination inorganic material, has good hydrophilicity and stability; Also have excellent character such as light transmission, chemical inertness, bio-compatibility simultaneously, these characteristics all make it have broad application prospects at aspects such as cell marking, medicament transport, DNA transfection and Selective Separation.
Summary of the invention
The object of the present invention is to provide a kind of method for preparing that can be used for the non-gathering alkoxyl of the water solublity substituted phthalocyanine-nano SiO 2 particle of optical dynamic therapy.
For realizing above-mentioned purpose, the present invention adopts following technical scheme:
The method for preparing of the non-gathering alkoxyl of a kind of water solublity substituted phthalocyanine-nano SiO 2 particle may further comprise the steps:
(1) under the room temperature, in 10 mL redistilled waters, adds 0.18 gram TBAB and 0.4mL n-butyl alcohol while stirring, behind the reaction 5-30 min, obtain the stabilized uniform microemulsion;
(2) continue to stir; In the microemulsion of step (1); The N that adds four-α-(2,2,4-trimethyl-3-amoxy) phthalocyanine metal complex successively; Dinethylformamide solution, ammonia, VTES and 3-aminopropyl triethoxysilane obtain clarifying green solution behind the reaction 15-40 h;
(3) green solution of dialysis step (2) promptly gets the aqueous solution of the non-gathering alkoxyl of described water solublity substituted phthalocyanine-nano SiO 2 particle.
The central metal of the described four-α of step (2)-(2,2,4-trimethyl-3-amoxy) phthalocyanine metal complex is Al.The N of described four-α-(2,2,4-trimethyl-3-amoxy) phthalocyanine metal complex, the volume ratio of dinethylformamide solution, ammonia, VTES and 3-aminopropyl triethoxysilane is 200:500:100～250:30; The N of described four-α-(2,2,4-trimethyl-3-amoxy) phthalocyanine metal complex, the concentration of dinethylformamide solution is 4 * 10 -3Mol/L.
The described dialysis time of step (3) is 48-80h.
Remarkable advantage of the present invention is:
Non-aggregation alkoxyl substituted phthalocyanine is wrapped up with nano SiO 2 particle, solved effectively and used limitation.At first, SiO is advanced in the phthalocyanine embedding 2In the nanostructured, can avoid the influence of the internal milieu factor of complicacy, improve the stability of phthalocyanine.Secondly, single SiO 2Can a large amount of highly active non-gathering phthalocyanine molecules of embedding in the nanoparticle.SiO 2Nanoparticle not only becomes the hydrophilic carrier of hydrophobicity photosensitizer, also is the medium that photosensitizer keeps non-coherent condition, makes nanoparticle have the ability than hyperfluorescence and generation singlet oxygen, is suitable for the analysis of high sensitivity fluorescence diagnosis.
Method for preparing of the present invention has been used the substituted phthalocyanine that has than the large space steric effect, and this type phthalocyanine has good anti-ability of aggregation in common organic solvent; But shortcoming is water insoluble; Through adopting two kinds of silane combineds effect, behind formation phthalocyanine-nano SiO 2 particle, the system that obtains is not only water-soluble; And phthalocyanine is non-state of aggregation therein, and the good generation singlet oxygen and the ability of emitting fluorescence are arranged.This is very beneficial for the application of this type phthalocyanine in PDT and PDD.
Description of drawings
Fig. 1 is the AlClPc (OR) that method provided by the invention is prepared 4-SiO 2The transmission electron microscope picture of nano-particle.
Fig. 2 is the AlClPc (OR) that method provided by the invention is prepared 4-SiO 2The electronic figure of nano-particle in water.
Fig. 3 is the AlClPc (OR) that method provided by the invention is prepared 4-SiO 2Nano-particle and the AlClPc of embedding silicon dioxide (OR) not 4Fluorescence spectrum figure in water or DMF: excitation wavelength 645 nm, (a) AlClPc (OR) 4/ DMF; (b) AlClPc (OR) 4-SiO 2Aqueous dispersions; (c) AlClPc (OR) 4/ DMF solution is dispersed in (C in the water AlClPc (OR) 4=4.54 * 10 -5Mol/L; V DMF/ V H2O=1/99).
Fig. 4 is the AlClPc (OR) that method provided by the invention is prepared 4-SiO 2Nano-particle is to the extra large firefly fluorescein analog chemiluminescent reinforced effects comparison diagram of photoinduction of (Cypridina Luciferin methoxy-analogue is called for short MCLA, and structure is as shown in Figure 5).Use therein is 708nm illumination.
Fig. 5 is the structure chart of MCLA.The chinesization formal name used at school of MCLA: 2-methyl-6-(4-anisyl)-3,7-glyoxalidine be [1,2-A] pyrazine-3-keto hydrochloride also.
Fig. 6 is the structural representation of four-α-(2,2,4-trimethyl-3-amoxy) aluminum phthalocyanine.
The specific embodiment
The method for preparing of the non-gathering phthalocyanine-nano SiO 2 particle of water solublity of the present invention comprises the following steps:
(1) microemulsion of preparation water, TBAB (CTAB), n-butyl alcohol;
(2) in above-mentioned microemulsion, add four-α-(2,2,4-trimethyl-3-amoxy) phthalocyanine metal complex (MPc (OR) 4) N, dinethylformamide (DMF) solution, ammonia, VTES (TEVS), 3-aminopropyl triethoxysilane (APTES), reaction obtains clarifying green solution;
(3) dialyse above-mentioned clarifying green solution except that desalting with bag filter, obtain phthalocyanine-silicon dioxide (MPc (OR) 4-SiO 2) aqueous solution of nano-particle.
Said bag filter is the specification of 14 kd-44 mm;
A period of time in the said step (1) is approximately 5-30 min;
The response time is about 15-40 h in the said step (2); The volume ratio of TEVS and APTES consumption is about 10:3 to 25:3;
A period of time is about 48-80 h in the said step (3).
Described non-gathering alkoxyl substituted phthalocyanine is four-α-(2,2,4-trimethyl-3-amoxy) phthalocyanine metal complex (MPc (OR) 4), central metal is an aluminum.
Embodiment 1
Under the continuous stirring condition of room temperature, in 10 ml redistilled waters, add 0.18 gram CTAB, 400 μ l n-butyl alcohol, mix 20 min after, obtain the stabilized uniform microemulsion.Continue to stir, add 200 μ l 4 * 10 successively -3The AlClPc of mol/L (OR) 4/ DMF, 500 μ l ammonia, 250 μ l TEVS, 30 μ l APTES continue reaction 20 h, obtain clarifying green solution.Behind solution 72 h that obtain with bag filter dialysis, obtain AlClPc (OR) 4-SiO 2The nano-particle aqueous solution.
Embodiment 2
Under the continuous stirring condition of room temperature, in 10 ml redistilled waters, add 0.18 gram CTAB, 400 μ l n-butyl alcohol, behind the mixing 5min, obtain the stabilized uniform microemulsion.Continue to stir, add 200 μ l 4 * 10 successively -3The AlClPc of mol/L (OR) 4/ DMF, 500 ul ammonia, 250 μ l TEVS, 30 μ l APTES continue reaction 30 h, obtain clarifying green solution.Behind solution 48 h that obtain with bag filter dialysis, obtain AlClPc (OR) 4-SiO 2The nano-particle aqueous solution.
Embodiment 3
Under the continuous stirring condition of room temperature, in 10 ml redistilled waters, add 0.18 gram CTAB, 400 μ l n-butyl alcohol, mix 30 min after, obtain the stabilized uniform microemulsion.Continue to stir, add 200 μ l 4 * 10 successively -3The AlClPc of mol/L (OR) 4/ DMF, 500 μ l ammonia, 100 μ l TEVS, 30 μ l APTES continue reaction 40 h, obtain clarifying green solution.Behind solution 56 h that obtain with bag filter dialysis, obtain AlClPc (OR) 4-SiO 2The nano-particle aqueous solution.
Embodiment 4
The AlClPc that method provided by the invention is prepared (OR) 4-SiO 2Nano-particle electronic figure such as Fig. 2 in water, AlClPc (OR) 4-SiO 2The concentration of nanoparticles solution is 4.54 * 10 -5Mol/L, the monomer absworption peak near infrared region 708nm place explains that it is in non-coherent condition among the figure.
Embodiment 5
The AlClPc that method provided by the invention is prepared (OR) 4-SiO 2Nano-particle and the AlClPc of embedding silicon dioxide (OR) not 4Fluorescence spectrum figure in water or DMF such as Fig. 3.
AlClPc (OR) 4In water, do not dissolve, so there is not fluorescence (curve C); And AlClPc (OR) 4-SiO 2Nano-particle is fluorescence strong (curve B) in water, approaches the AlClPc (OR) of same concentrations 4Fluorescence intensity in DMF (curve A).The prepared AlClPc (OR) of this figure explanation method provided by the invention 4-SiO 2Nano-particle has water solublity, and phthalocyanine wherein with in organic solvent (like DMF), similar existence form is arranged, be non-state of aggregation, so the fluorescent emission ability is stronger.
Embodiment 6
The AlClPc that method provided by the invention is prepared (OR) 4-SiO 2Nano-particle is to the chemiluminescent reinforced effects comparison diagram of photoinduction such as Fig. 4 of extra large firefly fluorescein analog MCLA.
Singlet oxygen can be induced the chemiluminescence of MCLA, among Fig. 4, as AlClPc (OR) 4-SiO 2In the time of the nano-particle coexistence, chemiluminescent intensity and the luminous speed of MCLA all significantly improve, and the AlClPc (OR) that the present invention prepares is described 4-SiO 2Nano-particle has the ability of stronger generation singlet oxygen.
The above is merely preferred embodiment of the present invention, and all equalizations of doing according to claim of the present invention change and modify, and all should belong to covering scope of the present invention.

Claims (4)

1. the method for preparing of the non-gathering alkoxyl of a water solublity substituted phthalocyanine-nano SiO 2 particle, it is characterized in that: described method for preparing may further comprise the steps:
(1) under the room temperature, in 10 mL redistilled waters, adds 0.18 gram TBAB and 0.4mL n-butyl alcohol while stirring, behind the reaction 5-30 min, obtain the stabilized uniform microemulsion;
(2) continue to stir; In the microemulsion of step (1); The N that adds four-α-(2,2,4-trimethyl-3-amoxy) phthalocyanine metal complex successively; Dinethylformamide solution, ammonia, VTES and 3-aminopropyl triethoxysilane obtain clarifying green solution behind the reaction 15-40 h;
(3) green solution of dialysis step (2) promptly gets the aqueous solution of the non-gathering alkoxyl of described water solublity substituted phthalocyanine-nano SiO 2 particle.
2. the method for preparing of the non-gathering alkoxyl of water solublity according to claim 1 substituted phthalocyanine-nano SiO 2 particle; It is characterized in that: step (2) described four-α-(2; 2,4-trimethyl-3-amoxy) central metal of phthalocyanine metal complex is Al.
3. the method for preparing of the non-gathering alkoxyl of water solublity according to claim 1 substituted phthalocyanine-nano SiO 2 particle; It is characterized in that: step (2) described four-α-(2; 2; 4-trimethyl-3-amoxy) N of phthalocyanine metal complex, the volume ratio of dinethylformamide solution, ammonia, VTES and 3-aminopropyl triethoxysilane is 200:500:100～250:30; The N of described four-α-(2,2,4-trimethyl-3-amoxy) phthalocyanine metal complex, the concentration of dinethylformamide solution is 4 * 10 -3Mol/L.
4. the method for preparing of the non-gathering alkoxyl of water solublity according to claim 1 substituted phthalocyanine-nano SiO 2 particle is characterized in that: the described dialysis time of step (3) is 48-80h.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103864833A (en) * 2014-03-24 2014-06-18 福州大学 Axial end hydroxyl substituted silicon phthalocyanine and self-assembling body thereof
CN108712916A (en) * 2016-03-01 2018-10-26 化学智能公司 Surgical examination gloves
JP7371476B2 (en) 2018-12-13 2023-10-31 東洋インキＳｃホールディングス株式会社 Near-infrared fluorescent composition and near-infrared fluorescent labeling agent

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103864833A (en) * 2014-03-24 2014-06-18 福州大学 Axial end hydroxyl substituted silicon phthalocyanine and self-assembling body thereof
CN103864833B (en) * 2014-03-24 2016-09-07 福州大学 A kind of axial end hydroxyl replaces silicon phthalocyanine and self-assembly thereof
CN108712916A (en) * 2016-03-01 2018-10-26 化学智能公司 Surgical examination gloves
JP7371476B2 (en) 2018-12-13 2023-10-31 東洋インキＳｃホールディングス株式会社 Near-infrared fluorescent composition and near-infrared fluorescent labeling agent

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