阅读说明：本技术 一种光还原自降解高分子及其制备方法和应用 (Photoreduction self-degradation polymer and preparation method and application thereof ) 是由 丁明明 翁闯 贺晓溶 刘信夫 张琴 谭鸿 傅强 于 2020-04-08 设计创作，主要内容包括：本发明涉及智能高分子材料领域,涉及一种光还原自降解高分子及其制备和应用。本发明提供一种光还原自降解高分子材料,所述材料的分子结构的主链含有还原敏感基团,支链含有光敏感基团,分子结构中还含有还原剂残基；所得材料在光刺激的作用下由于光敏感基团的脱除从而激活了还原剂残基,还原剂残基与还原敏感基团发生反应使得高分子材料的主链断裂,实现了高分子材料的还原降解。本发明所得光还原自降解高分子材料在还原性生理环境中能够响应细胞内水平的GSH实现主链的断裂；在缺乏还原剂的情况下,该聚合物在光照条件原位释放还原基团,同样能够实现主链的还原自降解。(The invention relates to the field of intelligent high polymer materials, and relates to a photoreduction self-degradation high polymer, and preparation and application thereof. The invention provides a photoreduction self-degradation high polymer material, wherein the main chain of the molecular structure of the material contains a reduction sensitive group, the branched chain contains a photosensitive group, and the molecular structure also contains a reducing agent residue; the obtained material activates the residue of the reducing agent due to the removal of the photosensitive group under the action of light stimulation, and the reducing agent residue reacts with the reduction sensitive group to break the main chain of the high polymer material, thereby realizing the reduction degradation of the high polymer material. The photoreduction self-degradation high polymer material obtained by the invention can respond to intracellular GSH to realize the main chain fracture in a reductive physiological environment; in the absence of a reducing agent, the polymer releases reducing groups in situ under the illumination condition, and the reduction self-degradation of the main chain can be realized.)

1. A photoreduction self-degradation high polymer material is characterized in that the main chain of the molecular structure of the photoreduction self-degradation high polymer material contains a reduction sensitive group, the branched chain contains a photosensitive group, and the molecular structure of the photoreduction self-degradation high polymer material also contains a reducing agent residue; the photoreduction self-degradation high polymer material activates a reducing agent residue due to the removal of photosensitive groups under the action of external light stimulation, and the reducing agent residue further reacts with reduction sensitive groups on the main chain to break the main chain of the high polymer material, so that the reduction degradation of the high polymer material is realized.

2. The photo-reductive self-degradable polymer material of claim 1, wherein the photosensitive group is selected from one of the following structural formulas:

in the formula, R₁Is a hydrogen atom orHetero substituent, R₂And R₃Is a hydrogen atom or an alkoxy group, R₂And R₃May be the same or different; the dotted line indicates the position of attachment to the reducing agent residue;

further, the reducing agent in the reducing agent residue is dithiothreitol, dithioerythritol or glutathione;

further, the reduction-sensitive group is a disulfide group or a diselenide group.

3. The method for preparing a photoreduction self-degradation high polymer material according to claim 1 or 2, which is characterized in that the method comprises the following steps: the reducing agent reacts with the substance containing the photosensitive group to obtain an intermediate, and the intermediate and the derivative thereof react with the substance containing the reduction sensitive group to obtain the photoreduction self-degradation high polymer material.

4. The method for preparing a photo-reductive self-degradable polymer material according to claim 3, wherein the reducing agent is dithiothreitol, dithioerythritol or glutathione;

further, the photosensitive group-containing substance is selected from one of the following compounds:

in the formula, R₁Is a hydrogen atom or an optional substituent, R₂And R₃Is a hydrogen atom or an alkoxy group, wherein R₂And R₃May be the same or different; x is a halogen atom;

further, the material containing the reduction-sensitive group is: a disulfide-or diselenide-containing diol, diamine, diacid, diisocyanate, or diacid halide compound;

further, the substance containing a reductively sensitive group is: dithiodiethanol, dithiodipropanol, dithiodiacetic acid, dithiodipropionic acid, cystamine, dithiodipropylamine, dithiodiphenylamine, cystamine diisocyanate, dithiodipropyl diisocyanate, dimethyl cystine diisocyanate, diethyl cystine diisocyanate, dimethyl homocystine diisocyanate, diethyl homocystine diisocyanate, dimethyl cystine, diethyl cystine, dimethyl homocystine, diethyl homocystine, di-tert-butoxycarbonyl cystine, dithiodibenzoyl chloride, dithiodiacetyl chloride, diselenediethanol, diselendipropanol, diselenediacetic acid, diselenedipropionic acid, selenocysteine, diselenedipropylamine, diselenodianiline, selenocysteine diisocyanate, diselenedipropyl diisocyanate, dimethyl selenocysteine diisocyanate, diethyl selenocysteine diisocyanate, dimethyl selenocysteine diisocyanate, One of selenocysteine diethyl diisocyanate, selenocysteine dimethyl ester, selenocysteine diethyl ester, di-tert-butoxycarbonyl selenocysteine, dithiodibenzoyl chloride or diselenedioyl chloride;

further, a reducing agent and a substance containing a photosensitive group are subjected to substitution reaction to obtain an intermediate;

further, the intermediate and the derivative thereof and a substance containing a reduction sensitive group are subjected to polyaddition, polycondensation or coupling reaction to obtain the photoreduction self-degradation high polymer material.

5. A drug carrier is characterized in that the drug carrier is a photoreduction self-degradation high polymer material/polyethylene glycol composition prepared by the condensation polymerization, polyaddition or coupling reaction of a photoreduction self-degradation high polymer material and polyethylene glycol and derivatives thereof; wherein the photoreduction self-degradation polymer material is the polymer material according to claim 1 or 2, or the polymer material prepared by the preparation method according to claim 3 or 4.

6. The photoreduction self-degradation high polymer material is used for self-assembly, biosensing or drug controlled release, and the photoreduction self-degradation high polymer material is the high polymer material in the claim 1 or 2, or the high polymer material prepared by the preparation method in the claim 3 or 4.

7. A method for improving the response efficiency of a reduction sensitive material, the method comprising: reducing agent residue is introduced into the molecular structure of the reduction sensitive material, and photosensitive groups are introduced into the branched chains; when the reduction sensitive material is under the action of light stimulation, the residue of the reducing agent is activated due to the removal of the photosensitive group, and the residue of the reducing agent further reacts with the reduction sensitive group on the main chain to break the main chain of the reduction sensitive material, so that the reduction degradation of the reduction sensitive material is realized.

8. The method of claim 7, wherein the photosensitive group is selected from one of the following formulas:

in the formula, R₁Is a hydrogen atom or an optional substituent, R₂And R₃Is a hydrogen atom or an alkoxy group, wherein R₂And R₃May be the same or different; the dotted line indicates the position of attachment to the reducing agent residue;

further, the reducing agent in the reducing agent residue is dithiothreitol, dithioerythritol or glutathione;

further, the reduction-sensitive material is: a disulfide-or diselenide-containing diol, diamine, diacid, diisocyanate, or diacid halide compound.

9. The method for improving the response efficiency of the reduction-sensitive material according to claim 7 or 8, wherein the method for improving the response efficiency of the reduction-sensitive material is as follows: firstly, a reducing agent is adopted to react with a substance containing a photosensitive group to obtain an intermediate, and then the intermediate and derivatives thereof are reacted with a substance containing a reduction sensitive group.

10. The method of claim 9, wherein the reducing agent is dithiothreitol, dithioerythritol, or glutathione;

further, the photosensitive group-containing substance is selected from one of the following compounds:

in the formula, R₁Is a hydrogen atom or an optional substituent, R₂And R₃Is a hydrogen atom or an alkoxy group, wherein R₂And R₃May be the same or different; x is a halogen atom;

further, the material containing the reduction-sensitive group is: dithiodiethanol, dithiodipropanol, dithiodiacetic acid, dithiodipropionic acid, cystamine, dithiodipropylamine, dithiodiphenylamine, cystamine diisocyanate, dithiodipropyl diisocyanate, dimethyl cystine diisocyanate, diethyl cystine diisocyanate, dimethyl homocystine diisocyanate, diethyl homocystine diisocyanate, dimethyl cystine, diethyl cystine, dimethyl homocystine, diethyl homocystine, di-tert-butoxycarbonyl cystine, dithiodibenzoyl chloride, dithiodiacetyl chloride, diselenediethanol, diselendipropanol, diselenediacetic acid, diselenedipropionic acid, selenocysteine, diselenedipropylamine, diselenodianiline, selenocysteine diisocyanate, diselenedipropyl diisocyanate, dimethyl selenocysteine diisocyanate, diethyl selenocysteine diisocyanate, dimethyl selenocysteine diisocyanate, One of selenocysteine diethyl diisocyanate, selenocysteine dimethyl ester, selenocysteine diethyl ester, di-tert-butoxycarbonyl selenocysteine, dithiodibenzoyl chloride or diselenedioyl chloride;

further, a reducing agent and a substance containing a photosensitive group are subjected to substitution reaction to obtain an intermediate;

further, the intermediate and the derivative thereof and a substance containing a reduction sensitive group carry out polyaddition, polycondensation or coupling reaction.

Technical Field

The invention relates to the technical field of intelligent high polymer materials, in particular to a photoreduction self-degradation high polymer and a preparation method and application thereof.

Background

The stimulus-responsive polymer materials have attracted great attention in the last decades, and they can receive stimulus signals from the external environment, and make their physical state or chemical structure change greatly, thereby affecting their physicochemical properties and functions, and thus having functions of sensing, processing, executing, etc. The nano self-assembly (micelle, microsphere, vesicle and the like) or hydrogel material prepared from the stimulus-response type high polymer material has wide application prospect in various fields of biosensing, drug release, bioengineering, chemical catalysis and the like.

The polymer nano system with the response capability to physiological endogenous stimuli such as pH, redox and enzyme has higher application value in the aspects of drug and gene delivery and the like, and becomes a research hotspot in the fields of materials science, biomedicine and pharmacy in recent years. However, the use effect of these bio-responsive polymeric materials in vivo faces a number of challenges. Firstly, endogenous stimuli are distributed heterogeneously among different individuals, tissues and organs and change continuously along with the progress of the disease, so that the specificity of stimulus response is not ideal. Secondly, due to the complexity of the organism, the levels of stimulatory factors in different cells and organelles are not balanced and are always in a dynamically changing state. In addition, the sustained reaction of the bioresponse material system with the body may further deplete the stimulus, leading to a decrease in response efficiency. More importantly, most sensitive groups of the stimuli-responsive polymer nano-material are positioned in a hydrophobic core or shielded by a protective shell, so that steric hindrance is brought to attack of water molecules, Glutathione (GSH), enzymes and other biomacromolecules. Therefore, it is of great interest to design novel smart materials to overcome the spatiotemporal barriers to stimulus response.

The illumination is used as a common exogenous environmental stimulus, can avoid the influence caused by the change of the physiological environment in vivo, has the characteristics of accurately controlling time, position and dosage, high efficiency and the like, and has certain advantages compared with other types of environmental stimuli. However, the existing photosensitive materials change the hydrophilicity and hydrophobicity of macromolecules and the interaction between molecules mainly through the shedding or isomerization of photoresponsive groups, thereby causing the structural change of self-assemblies, and causing the drug release efficiency to be low. The main chain photodegradable polymer can realize the complete degradation of the main chain only by introducing a large amount of photosensitive groups into the main chain of the polymer, thereby having great influence on the physicochemical property and biocompatibility of the matrix and limiting the types of the photosensitive polymers. On the other hand, the existing photosensitive polymer material mainly depends on exogenous stimulation, and cannot make adjustment and cooperative response according to the stimulation level in a living body, so that the intelligence and the response efficiency are to be improved.

Disclosure of Invention

Aiming at the problems in the prior art, the invention provides a photoreduction self-degradation high polymer material, wherein a stimulus source and a reduction sensitive group are introduced into a high polymer structure together, and a photosensitive group for shielding the stimulus source is introduced into a branched chain of the high polymer, so that the photoreduction self-degradation material is obtained; the photoreduction self-degradation high polymer material can respond to intracellular GSH to realize the breakage of a main chain in a normal reductive physiological environment; in the absence of a reducing agent, the polymer can release a reducing group in situ under the illumination condition, and the reduction self-degradation of the main chain can be realized.

The technical scheme of the invention is as follows:

the first technical problem to be solved by the invention is to provide a photoreduction self-degradation high polymer material, wherein the main chain of the molecular structure of the photoreduction self-degradation high polymer material contains a reduction sensitive group, the branched chain contains a photosensitive group, and the molecular structure of the photoreduction self-degradation high polymer material also contains a reducing agent residue; the photoreduction self-degradation high polymer material activates a reducing agent residue due to the removal of photosensitive groups under the action of external light stimulation, and the reducing agent residue further reacts with reduction sensitive groups on the main chain to break the main chain of the high polymer material, so that the reduction degradation of the high polymer material is realized.

Further, the photosensitive group is selected from one of the following structural formulas:

in the formula, R₁Is a hydrogen atom or an optional substituent, R₂And R₃Is a hydrogen atom or an alkoxy group, R₂And R₃May be the same or different; the dotted line indicates the position of attachment to the reducing agent residue.

Further, the reducing agent residue refers to: in the process of forming the molecular structure of the self-degradation high polymer material by the reducing agent participating in photoreduction, the residual structure of the reducing agent except the groups participating in the reaction is the residue of the reducing agent.

Further, the reducing agent in the reducing agent residue is Dithiothreitol (DTT), Dithioerythritol (DTE), or Glutathione (GSH).

Further, the reduction-sensitive group is a disulfide group or a diselenide group.

The second technical problem to be solved by the present invention is to provide a method for preparing the photo-reduction self-degradation polymer material, wherein the method comprises: the reducing agent reacts with the substance containing the photosensitive group to obtain an intermediate, and the intermediate and the derivative (intermediate or intermediate derivative) thereof react with the substance containing the reduction sensitive group to obtain the photoreduction self-degradation high polymer material.

Further, in the above method, the reducing agent is Dithiothreitol (DTT), Dithioerythritol (DTE), or Glutathione (GSH).

Further, in the above method, the photosensitive group-containing substance is selected from one of the following compounds:

in the formula, R₁Is a hydrogen atom or an optional substituent, R₂And R₃Is a hydrogen atom or an alkoxy group, wherein R₂And R₃May be the same or different; x is a halogen atom.

Further, in the above method, the substance containing a reduction-sensitive group is: a disulfide-or diselenide-containing diol, diamine, diacid, diisocyanate, or diacid halide compound.

Further, the substance containing a reductively sensitive group is: dithiodiethanol, dithiodipropanol, dithiodiacetic acid, dithiodipropionic acid, cystamine, dithiodipropylamine, dithiodiphenylamine, cystamine diisocyanate, dithiodipropyl diisocyanate, dimethyl cystine diisocyanate, diethyl cystine diisocyanate, dimethyl homocystine diisocyanate, diethyl homocystine diisocyanate, dimethyl cystine, diethyl cystine, dimethyl homocystine, diethyl homocystine, di-tert-butoxycarbonyl cystine, dithiodibenzoyl chloride, dithiodiacetyl chloride, diselenediethanol, diselendipropanol, diselenediacetic acid, diselenedipropionic acid, selenocysteine, diselenedipropylamine, diselenodianiline, selenocysteine diisocyanate, diselenedipropyl diisocyanate, dimethyl selenocysteine diisocyanate, diethyl selenocysteine diisocyanate, dimethyl selenocysteine diisocyanate, One of selenocysteine diethyl diisocyanate, selenocysteine dimethyl ester, selenocysteine diethyl ester, di-tert-butoxycarbonyl selenocysteine, dithiodibenzoyl chloride or diselenedioyl chloride.

Further, in the above method, the reducing agent and the substance containing a photosensitive group are subjected to substitution reaction to obtain an intermediate.

Further, in the method, the intermediate and the derivative thereof react with a substance containing a reduction sensitive group through addition polymerization, polycondensation or coupling to obtain the photoreduction self-degradation high polymer material.

The third technical problem to be solved by the invention is a drug carrier, wherein the drug carrier is a photoreduction self-degradation polymer material/polyethylene glycol composition prepared by the photoreduction self-degradation polymer material and polyethylene glycol and derivatives thereof through polycondensation, polyaddition or coupling reaction.

The fourth technical problem to be solved by the present invention is to provide the use of the photo-reduction self-degradation polymer material, which is used in self-assembly, biosensing or controlled drug release.

The fifth technical problem to be solved by the invention is a method for improving the response efficiency of a reduction sensitive material, which comprises the following steps: reducing agent residue is introduced into the molecular structure of the reduction sensitive material, and photosensitive groups are introduced into the branched chains; when the reduction sensitive material is under the action of light stimulation, the residue of the reducing agent is activated due to the removal of the photosensitive group, and the residue of the reducing agent further reacts with the reduction sensitive group on the main chain to break the main chain of the reduction sensitive material, so that the reduction degradation of the reduction sensitive material is realized.

Further, in the method for improving the response efficiency of the reduction-sensitive material, the photosensitive group is selected from one of the following structural formulas:

in the formula, R₁Is a hydrogen atom or an optional substituent, R₂And R₃Is a hydrogen atom or an alkoxy group, wherein R₂And R₃May be the same or different; the dotted line indicates the position of attachment to the reducing agent residue.

Further, in the above method for improving the response efficiency of the reduction-sensitive material, the reducing agent residue refers to: in the process of forming the molecular structure of the self-degradation high polymer material by the reducing agent participating in photoreduction, the residual structure of the reducing agent except the groups participating in the reaction is the residue of the reducing agent.

Further, the reducing agent in the reducing agent residue is Dithiothreitol (DTT), Dithioerythritol (DTE), or Glutathione (GSH).

Further, the reduction-sensitive material is: a disulfide-or diselenide-containing diol, diamine, diacid, diisocyanate, or diacid halide compound.

Further, the specific method for improving the response efficiency of the reduction sensitive material comprises the following steps: firstly, a reducing agent is adopted to react with a substance containing a photosensitive group to obtain an intermediate, and then the intermediate and a derivative (intermediate or intermediate derivative) thereof are reacted with a substance containing a reduction sensitive group.

Further, in the method for improving the response efficiency of the reduction sensitive material, the reducing agent is Dithiothreitol (DTT), Dithioerythritol (DTE) or Glutathione (GSH).

Further, in the method for improving the response efficiency of the reduction-sensitive material, the substance containing a photosensitive group is selected from one of the following compounds:

in the formula, R₁Is a hydrogen atom or an optional substituent, R₂And R₃Is a hydrogen atom or an alkoxy group, wherein R₂And R₃May be the same or different; x is a halogen atom.

Further, in the method for improving the response efficiency of the reduction-sensitive material, the substance containing the reduction-sensitive group is: a disulfide-or diselenide-containing diol, diamine, diacid, diisocyanate, or diacid halide compound.

Further, the substance containing a reductively sensitive group is: dithiodiethanol, dithiodipropanol, dithiodiacetic acid, dithiodipropionic acid, cystamine, dithiodipropylamine, dithiodiphenylamine, cystamine diisocyanate, dithiodipropyl diisocyanate, dimethyl cystine diisocyanate, diethyl cystine diisocyanate, dimethyl homocystine diisocyanate, diethyl homocystine diisocyanate, dimethyl cystine, diethyl cystine, dimethyl homocystine, diethyl homocystine, di-tert-butoxycarbonyl cystine, dithiodibenzoyl chloride, dithiodiacetyl chloride, diselenediethanol, diselendipropanol, diselenediacetic acid, diselenedipropionic acid, selenocysteine, diselenedipropylamine, diselenodianiline, selenocysteine diisocyanate, diselenedipropyl diisocyanate, dimethyl selenocysteine diisocyanate, diethyl selenocysteine diisocyanate, dimethyl selenocysteine diisocyanate, One of selenocysteine diethyl diisocyanate, selenocysteine dimethyl ester, selenocysteine diethyl ester, di-tert-butoxycarbonyl selenocysteine, dithiodibenzoyl chloride or diselenedioyl chloride.

Furthermore, in the method for improving the response efficiency of the reduction sensitive material, the reducing agent and the substance containing the photosensitive group are subjected to substitution reaction to obtain an intermediate.

Further, in the above method for improving the response efficiency of the reduction-sensitive material, the intermediate and the derivative thereof undergo addition polymerization, polycondensation or coupling reaction with a substance containing a reduction-sensitive group.

The invention has the beneficial effects that:

compared with the prior art, the invention has the following advantages:

(1) the invention provides a photoreduction self-degradation material, which comprises a stimulus source and a reduction sensitive group in a molecular structure, wherein a branched chain comprises a photosensitive group for shielding the stimulus source; so that the obtained photoreduction self-degradation high polymer material can respond to intracellular level GSH to realize the main chain fracture in a normal reductive physiological environment; in the absence of a reducing agent, the polymer can generate a stimulus in situ under the condition of illumination, and the reductive self-degradation of the main chain can be realized. Therefore, the problems of timing fixed-point and on-demand response, steric hindrance obstacle, permeability obstacle, concentration obstacle and the like of stimulus response are solved, higher response efficiency than that of the traditional reduction sensitive and photosensitive material is obtained, and the required stimulus source concentration is far lower than that of an external reducing agent.

(2) The photoreduction self-degradation high polymer material of the invention introduces photosensitive groups on the side chains, and the photosensitive groups are on the side chains, but can realize the main chain degradation, thereby avoiding the need of introducing complex photodegradation groups on the main chain in the traditional photodegradation high polymer, and the method is easier to expand to other high polymer systems.

(3) The reduction sensitive material provided by the invention can be degraded into small molecular substances by photoreduction, has higher biocompatibility and is easy to be eliminated and metabolized by organisms.

(4) The reduction sensitive material provided by the invention can be introduced into various environment sensitive polymer systems as an intelligent response block.

(5) The reduction sensitive material provided by the invention can be widely applied to the biomedical fields and industrial fields of biosensing, self-assembly, drug controlled release and the like.

The photosensitive group is introduced into the reduction sensitive material, so that a stimulus source protected by a photosensitizer and the reduction sensitive group are introduced into a high molecular chain together, and the reduction sensitive high molecular material can respond to intracellular GSH to realize the breakage of the main chain in a normal reduction physiological environment; under the condition of lacking a reducing agent, the polymer can release reducing groups under the condition of illumination, and the reduction self-degradation of the main chain can be realized; therefore, the reduction sensitive polymer material can effectively overcome time obstacle, concentration obstacle and space obstacle of stimulus response, and synergistically integrate endogenous stimulus and exogenous stimulus, thereby greatly improving the intelligence and response efficiency of the molecular material, and having better application potential in the fields of self-assembly, biosensing, drug delivery, disease diagnosis and treatment and the like.

Drawings

FIG. 1 is a photograph of photo-reduced self-degradable polymer 1 coated potassium bromide salt tablet prepared in example 1 before and after UV irradiation, wherein the left side is before irradiation and the right side is after irradiation.

FIG. 2 is FTIR spectra of photo-reduced self-degraded polymer 1 prepared in example 1 under UV illumination for different time periods: a-0min, b-15min, c-30min, d-60min and e-120 min.

FIG. 3 is a graph showing UV absorption spectra of the photo-reduced self-degradable polymer 1 solution prepared in example 1 at different time points of illumination, wherein the upper right graph shows the absorbance at 307nm as a function of time.

FIG. 4 is a graph showing a distribution of particle sizes of self-assembled bodies of photo-reduced self-degradable polymers 11 prepared in example 11.

FIG. 5 is a transmission electron micrograph of a self-assembled photo-reduced self-degradable polymer 11 prepared in example 11.

FIG. 6 is an FTIR spectrum of photo-reduced self-degraded polymer 11 prepared in example 11 under different time periods of UV illumination: a-0min, b-15min, c-30min, d-60min and e-120 min.

FIG. 7 is a photograph of the deuterated dimethyl sulfoxide solution of the photo-reduced self-degradable polymer 11 prepared in example 11 under different illumination times: a-0min, b-15min, c-30min, d-60min and e-120 min. .

FIG. 8 is a nuclear magnetic hydrogen spectrum of photo-reduced self-degradable polymer 11 prepared in example 11 under light for different periods of time: a-0min, b-15min, c-30min, d-60min, e-120 min; the right image is a local enlarged spectrogram.

FIG. 9 shows GPC charts of a photo-reductive self-degradable polymer 11 prepared in example 11 before (a) and after (b) photo-reductive degradation, and a c-curve is a GPC curve of a methoxypolyethylene glycol monomer.

FIG. 10 is a mass spectrum of the photo-reductive degradation product of the self-degradable polymer 11 prepared in example 11.

FIG. 11(A) is a graph showing UV absorption spectra of a solution of photo-reducible self-degradable polymer 11 prepared in example 11 at different time points under UV irradiation, and FIG. 11(B) is a graph showing UV absorption spectra of a self-assembled body of photo-reducible self-degradable polymer 11 prepared in example 11 at different time points under UV irradiation; the upper right-hand curve in the figure is the absorbance at 307nm as a function of time.

FIG. 12 is a transmission electron micrograph of a self-assembly of the photo-reduced self-degradable polymer 11 prepared in example 11 after irradiation with light.

FIG. 13 is a graph of fluorescence spectra of different photosensitive self-assemblies encapsulated with Nile Red under UV illumination for different time periods: wherein FIG. 13A is a photo-reductive self-degradable polymer 11 self-assembly prepared in example 11; FIG. 13B is a conventional light-sensitive polymeric self-assembly prepared in comparative example 1; FIG. 13C is a graph showing a fluorescence spectrum of the self-assembled photo-reduced self-degradable polymer 11 prepared in example 11 with the addition of 10mM DTT; FIG. 13D is a normalized plot of fluorescence intensity at 633nm versus time for three different self-assembly fluorescence spectra, where a, b, and C correspond to the samples in A, B and C, respectively, above.

FIG. 14 is the release profile of the photo-reduced self-degradable polymer 11 self-assembly prepared in example 11 after loading DOX in PBS buffer under different conditions: a-no light, b-light, c-plus 10mM GSH.

FIG. 15 is a photograph of the photo-reduced self-degradable polymer 11 self-assembly prepared in example 11 after being coated with DOX and subjected to different treatments: (A) before treatment, (B) 10mM GSH is added, (C) ultraviolet light is irradiated, and (D) blank self-assembly bodies without medicines are loaded.

FIG. 16 is a fluorescence spectrum (excitation wavelength: 480nm) of the photo-reduced self-degradable polymer 11 prepared in example 11 after encapsulation of DOX and Cy5 with UV light at different times: a-0min, b-15min, c-30min, d-60min and e-120 min.

FIG. 17 is a graph showing the FRET reduction efficiency with time of the self-assembly of photo-reduced self-degradable polymer 11 prepared in example 11 after loading DOX and Cy5 under UV irradiation (a) and with the addition of 10mM DTT (b).

FIG. 18 is a CLSM photograph of tumor cells after DOX is encapsulated in the self-assembly of photo-reducing self-degradable polymer 11 prepared in example 11 and co-cultured with MCF-7 tumor cells for 4 hours; where red is DOX and blue is DAPI stained nuclei.

FIG. 19 is a CLSM photograph of the self-assembly of photo-reduced self-degradable polymer 11 prepared in example 11, which is loaded with DOX and Cy5, co-cultured with MCF-7 tumor cells for 1 hour (a), then irradiated with light for 4 minutes (c) or not (b), and further cultured for 3 hours; where red is DOX, green is Cy5, yellow is FRET fluorescence, and blue is DAPI stained nuclei.

FIG. 20 shows the cell survival rate measured by MTT method after DOX is encapsulated in the self-assembly of photo-reduced self-degradable polymer 11 prepared in example 11, diluted by different times and co-cultured with MCF-7 tumor cells for 48 hours, wherein a-is not irradiated, b-is irradiated for 4 minutes, and c-is free DOX control.

FIG. 21 shows the cell survival rate of the photoreduction self-degradable polymer 11 self-assembly prepared in example 11, which was measured by a-4 min illumination and b-no illumination, after dilution with different fold and co-culture with MCF-7 tumor cells for 48 hours using the MTT method.

Detailed Description

The mechanism of the invention is as follows:

taking embodiment 1 as an example, the present invention provides a photoreduction self-degradation material, wherein a molecular chain of the photoreduction self-degradation material contains a reducing agent DTT residue, a main chain of the photoreduction self-degradation material contains a reduction-sensitive disulfide group, and a branched chain of the photoreduction self-degradation material contains a photosensitive o-nitrobenzene (ONB) group for shielding DTT activity; the photoreduction self-degradation high polymer material can respond to GSH (10mM) in the level of tumor cells in a normal reductive physiological environment to realize the fragmentation of a main chain; in the absence of a reducing agent, the polymer can be subjected to ONB removal under the illumination condition, active DTT residues are generated in situ, disulfide groups of a main chain are attacked, and then the reduction self-degradation of the main chain can be realized.