CN111773184B - Hypoxic response liposome and application thereof in preparation of antitumor drugs - Google Patents

Hypoxic response liposome and application thereof in preparation of antitumor drugs Download PDF

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CN111773184B
CN111773184B CN202010676032.9A CN202010676032A CN111773184B CN 111773184 B CN111773184 B CN 111773184B CN 202010676032 A CN202010676032 A CN 202010676032A CN 111773184 B CN111773184 B CN 111773184B
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azobenzene
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polyethylene glycol
drug
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CN111773184A (en
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姜新义
陈晨
唐春伟
杜微
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Nanjing Kaima Biotechnology Co.,Ltd.
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Abstract

The invention particularly relates to a hypoxic response liposome and application thereof in preparation of antitumor drugs. Many disease symptoms are accompanied by hypoxia, and in view of this phenomenon, the present invention aims to provide a liposome having a hypoxia response effect. Based on the aim, the invention provides the liposome taking the azobenzene compound, the phospholipid and the cholesterol as raw materials, wherein azobenzene has a low-oxygen response effect, and the surface of the azobenzene is modified by a hydrophobic material and a hydrophilic material, so that the self-assembly effect of the liposome raw materials can be realized. The hypoxic response liposome can be used as a drug carrier to efficiently target tumor tissues, and the azobenzene compound is automatically broken under the hypoxic condition, so that a phospholipid bilayer of the liposome is damaged, and drug release is realized. The hypoxia response liposome can effectively improve the utilization rate of the drug as a carrier of anti-tumor and cardiovascular disease treatment drugs, and has good application prospect.

Description

Hypoxic response liposome and application thereof in preparation of antitumor drugs
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a hypoxic response liposome and application thereof in preparation of antitumor drugs.
Background
The information in this background section is only for enhancement of understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.
Hypoxia is mainly caused by insufficient oxygen supply and is a typical characteristic of various diseases, such as malignant tumor, heart disease, vascular diseases and the like. Especially in malignant tumor tissue, the tumor cells are rapidly proliferated to consume oxygen, and the uneven growth and distribution of blood vessels inhibit the supply of oxygen, so that the malignant tumor tissue is in a relatively serious hypoxia state for a long time. Therefore, the hypoxic characteristic of the tumor part can be utilized to deliver the drug to the tumor part in a targeted way, and the dosage of the drug and the damage to normal tissues are reduced.
Liposomes (liposomes) are amphiphilic molecules such as phospholipids and sphingolipids that are dispersed in an aqueous phase, the hydrophobic tails of the molecules tend to clump together, avoiding the aqueous phase, while the hydrophilic heads are exposed to the aqueous phase, forming closed vesicles with a bilayer structure. The liposome can be used for delivering genes, medicaments and the like, and the medicaments are delivered into cells by utilizing the characteristic that the liposome can be fused with cell membranes.
Azobenzene derivative (AZO) has nitrogen-nitrogen double bonds, is easy to lose electrons and break in a low-oxygen-content environment, and therefore has an oxygen-deficient response characteristic. The azobenzene derivative has good symmetry, and can be respectively connected with hydrophilic substances and hydrophobic substances on two sides to synthesize an anaerobic responsive amphiphilic material. The hypoxia-responsive amphiphilic material can form a core-shell structure through self-assembly or be assembled into a liposome with other substances, such as cholesterol, so that the function of the liposome is improved, and the hypoxia-responsive amphiphilic material can be used for drug delivery.
Disclosure of Invention
Based on the above-mentioned background art, the present invention aims to provide a liposome which can target tumor tissues and achieve a drug-targeted release effect. Based on the technical purpose, the invention adopts azobenzene as a hypoxic response element, thereby realizing the response and directional release effects of the liposome to the hypoxic environment.
Based on the technical effects, the invention provides the following technical scheme:
according to the first aspect of the invention, azobenzene compounds are embedded between phospholipid bilayers of the liposome, azobenzene or derivatives thereof are used as frameworks of the azobenzene compounds, and hydrophobic materials and hydrophilic materials are respectively connected with two ends of the azobenzene compounds to form hydrophobic ends and hydrophilic ends of the azobenzene compounds.
Aiming at the hypoxic response element of the hypoxic response liposome, azobenzene and derivatives thereof are used as a skeleton, and the azobenzene is modified to have a hydrophilic end and a hydrophobic end, so that the azobenzene can be automatically loaded between phospholipid bilayers in the mixing process of the azobenzene, the phospholipid and cholesterol, and the hydrophilic end is exposed out of the liposome. When the liposome is transported to a hypoxic environment tissue along with blood circulation, an azobenzene substance in the azobenzene compound can respond to an oxygen-absorbing environment to break, so that a phospholipid bilayer structure of the liposome is damaged, and the drug entrapped in the liposome is released.
In a second aspect of the present invention, there is provided a method for preparing the hypoxic responsive liposome of the first aspect, the method comprising the steps of:
in a third aspect of the invention, the hypoxic responsive liposome of the first aspect is provided for use as a targeted drug carrier.
The beneficial effects of one or more technical schemes are as follows:
the invention designs and synthesizes the lipidosome with the hypoxic response effect for the first time, the lipidosome is modified by the hypoxic response effect of azobenzene, so that the self-assembly of the lipidosome is realized, the directional release of the medicament can be really realized based on the hypoxia induction, and the lipidosome is assembled with cholesterol, lecithin, cephalin, soybean phospholipid, synthetic phospholipid and the like to improve the function of the lipidosome, can be used for medicament delivery, is broken at an anoxic part, and increases the accumulation of the medicament at the anoxic part and the targeting property of the medicament delivery. The research result has important implication for the research of targeted liposome.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the invention and together with the description serve to explain the invention and not to limit the invention.
Fig. 1 is a schematic structural diagram of the hypoxic responsive liposome described in example 2.
FIG. 2 shows IR-NH as described in example 12LC-MS diagram of (1).
FIG. 3 is a photograph of PEG-AZO as described in example 11H-NMR chart.
FIG. 4 shows the preparation of PEG-AZO-IR as described in example 11H-NMR chart.
FIG. 5 is a morphology of blank liposomes detected by DLS and TEM in example 2;
wherein the scale bar of the TEM image is 1 mm: 200 nm.
FIG. 6 is a graph of bioluminescence imaging in orthotopic colon cancer mice of example 3 in different treatment groups.
Detailed Description
It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.
As described in the background, to solve the above technical problems, the present invention proposes a hypoxic responsive liposome.
According to the first aspect of the invention, azobenzene compounds are embedded between phospholipid bilayers of the liposome, azobenzene or derivatives thereof are used as frameworks of the azobenzene compounds, and hydrophobic materials and hydrophilic materials are respectively connected with two ends of the azobenzene compounds to form hydrophobic ends and hydrophilic ends of the azobenzene compounds.
Preferably, the azobenzene skeleton and the hydrophobic end are positioned between the phospholipid bilayers of the liposome, and the hydrophilic end extends out of the phospholipid bilayers and is positioned outside the liposome.
Preferably, the skeleton is Azobenzene (AZO), but is not limited to 4, 4' -dicarboxylazobenzene, and may be other derivatives of azobenzene.
Preferably, the hydrophilic material is polyethylene glycol (PEG).
According to the research structure of the invention, the liposome prepared by adopting polyethylene glycol has the most stable structure, and the polyethylene glycol has low cost, easy obtaining and safe use.
Preferably, the hydrophobic material is one of substances including, but not limited to, high molecular polymers, liposoluble drugs, oleic acid, vitamin E, photosensitizers, and the like. The selection of the hydrophobic material by those skilled in the art can be adjusted according to the physicochemical properties of the hypoxic responsive liposome.
In some embodiments of the above preferred embodiments, the hydrophobic material is a lipid-soluble drug, and can also serve as a hydrophobic end to promote liposome self-assembly while playing a therapeutic role.
In some embodiments of the above preferred embodiments, the hydrophobic material is a photosensitizer, and the photosensitizer undergoes a photodynamic reaction at a specific wavelength to generate singlet oxygen to exert its tumor cell destroying effect. Specifically, the photosensitizer includes, but is not limited to, HpD, porphyrin, chlorophyll degradation derivatives, benzoporphyrin derivatives, 5-aminolevulinic acid, hypocrellin or polypeptide, and the like.
In a second aspect of the present invention, there is provided a method for preparing the hypoxic responsive liposome of the first aspect, the method comprising the steps of:
and dissolving the azobenzene compound, phospholipid and cholesterol in an organic solvent, drying to form a film, and extruding to obtain the hypoxic response liposome.
In some embodiments of the above preparation method, the hydrophobic end of the azobenzene complex is the photosensitizer IR780, the skeleton is azobenzene, the hydrophilic end is polyethylene glycol, and the hypoxic response liposome is prepared as follows: modifying the photosensitizer IR toIR-NH2The preparation method comprises the following steps of carrying out condensation reaction on polyethylene glycol and azobenzene to form polyethylene glycol-azobenzene, further obtaining a polyethylene glycol-azobenzene-photosensitizer IR compound through amidation reaction, dissolving the polyethylene glycol-azobenzene-photosensitizer IR compound, phospholipid and cholesterol in an organic solvent, removing the solvent to obtain a lipid membrane, and extruding to obtain the hypoxia response liposome.
In the above embodiment, the photosensitizer IR and 3-amino-1-propanol are stirred at 80-90 ℃ in a dark condition for 5-7 hours, and the prepared crude product is purified by silica gel column and gradient eluted by methanol and Dichloromethane (DCM).
In the above embodiment, the polymerization degree of the polyethylene glycol is 25 to 30.
Specifically, the polyethylene glycol is polyethylene glycol 2000.
In the above embodiment, the polyethylene glycol-azobenzene is synthesized as follows: dissolving polyethylene glycol and azobenzene in a mixed solution of dichloromethane and trichloromethane, adding a catalyst and a dehydrating agent, and stirring for reaction at room temperature.
In the above embodiment, in the polyethylene glycol-azobenzene-photosensitizer IR complex, the molar ratio of the polyethylene glycol, azobenzene and photosensitizer is 0.8 to 1.2: 5: 0.8 to 1.2.
In the above embodiment, the organic solvent is ethanol.
In a third aspect of the invention, the hypoxic responsive liposome of the first aspect is provided for use as a targeted drug carrier.
Preferably, in the application, the medicament is used for treating diseases showing a hypoxic state, and comprises but is not limited to anti-tumor medicaments and anti-cardiovascular disease medicaments; further preferably, the drug is an antitumor drug.
Preferably, in the application, when the hydrophobic end material of the azobenzene compound is a photosensitizer, the targeting property is improved by applying light with a specific wavelength to the affected part.
In order to make the technical solution of the present invention more clearly understood by those skilled in the art, the technical solution of the present invention will be described in detail with reference to specific examples, wherein the reagents described in the following examples are all commercially available products.
EXAMPLE 1 Synthesis of PEG-AZO-IR
0.6mmol IR and 3mmol 3-amino-1-propanol were dissolved in 20mL anhydrous DMF and 170. mu.L Triethylamine (TEA) was added. The reaction was stirred in the dark at 85 ℃ for 6 hours. The crude product was purified by column on silica gel eluting with a gradient of methanol and Dichloromethane (DCM) to give IR-NH2. LC-MS further confirmed the synthetic IR-NH2Success (fig. 2).
PEG (150mg, 0.075mmol) and AZO (75mg, 0.375mmol) were dissolved in DCM and chloroform (TCM) (VDCM: VTCM ═ 1: 1) and then DMAP (11mg, 0.09mmol) and DCC (15.5mg, 0.075mmol) were added. The reaction was stirred at Room Temperature (RT) for 24 h. The product PEG-AZO was obtained by precipitation 3 times in cold ether. H-NMR further confirmed the success of the synthesized PEG-AZO (FIG. 3).
To the solution containing 0.02mmol PEG-AZO and 0.02mmol IR-NH2To the mixture solution of DCM and TCM, 0.024mmol of DMAP and 0.02mmol of DCC were added, followed by stirring at room temperature for 24 hours. The product was then rotary evaporated and precipitated with cold ether.1H-NMR further confirmed the success of the synthesized PEG-AZO-IR (FIG. 4).
Example 2 preparation and characterization of hypoxic responsive liposomes
SPC, cholesterol and PEG-AZO-IR (8: 1: 1, w/w/w) were dissolved in ethanol, and the ethanol was dried by rotary evaporator to form a lipid film. It was then extruded tens of times through a 200nm membrane using a hand-held liposome extruder. The mean diameter of the blank liposomes was 153.3nm as determined by TEM and DLS (fig. 5).
Example 3 application of hypoxic responsive liposomes in the preparation of antitumor drugs
In this example, a novel encapsulated BMS (PD-L1 inhibitor) antitumor drug liposome (HLB) was first provided, SPC, cholesterol, PEG-AZO-IR and BMS were mixed according to a 64: 8: 8: 1.5, w/w/w/w, and then dried by a rotary evaporator to form a lipid film. Then extruding the liposome through a 200nm membrane for tens of times by using a handheld liposome extruder to obtain the antitumor drug liposome (HLB).
This example also evaluates the antitumor activity of the antitumor drug liposome (HLB) by in vivo experiments. An in situ CRC model was established by injecting murine CT26 colon cancer cells into the cecal wall of BALB/C mice. Mice were randomized into groups prior to treatment with PBS, HLB. Next, 7d after the in situ tumor cell inoculation, PBS and HLB were intravenously injected on days 8, 11, 14, 17 and 20, respectively (the tumor site was irradiated with laser light at 1W/cm after 8 hours of intravenous administration)210 min). Tumor burden was monitored using bioluminescence imaging to assess treatment efficacy. The results are shown in fig. 6, where HLB showed significant tumor growth inhibition. The IR-containing liposome preparation of the present invention is demonstrated to have excellent potential application in photothermal therapy of cancer as an effective photothermal agent.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. An azobenzene compound is embedded between phospholipid bilayer layers of the liposome, azobenzene is used as a skeleton of the azobenzene compound, and two ends of the azobenzene compound are respectively connected with a hydrophobic material and a hydrophilic material to form a hydrophobic end and a hydrophilic end of the azobenzene compound; the hydrophilic material is polyethylene glycol, and the hydrophobic material is a photosensitizer IR 780;
the azobenzene skeleton and the hydrophobic end are positioned between the phospholipid bilayers of the liposome, and the hydrophilic end extends out of the phospholipid bilayers and is positioned outside the liposome.
2. The method for preparing hypoxic responsive liposome according to claim 1, wherein the method comprises the following steps:
and dissolving the azobenzene compound, phospholipid and cholesterol in an organic solvent, drying to form a film, and extruding to obtain the hypoxic response liposome.
3. The method for preparing hypoxic-responsive liposome according to claim 2, wherein photosensitizer IR780 is modified to IR-NH2The preparation method comprises the following steps of carrying out condensation reaction on polyethylene glycol and azobenzene to form polyethylene glycol-azobenzene, further obtaining a polyethylene glycol-azobenzene-photosensitizer IR compound through amidation reaction, dissolving the polyethylene glycol-azobenzene-photosensitizer IR compound, phospholipid and cholesterol in an organic solvent, removing the solvent to obtain a lipid membrane, and extruding to obtain the hypoxia response liposome.
4. The method for preparing hypoxic-responsive liposome according to claim 3, wherein photosensitizer IR780 is modified to IR-NH2The method comprises the following steps: placing the photosensitizer IR780 and 3-amino-1-propanol under a dark condition, stirring at 80-90 ℃ for 5-7 hours, purifying the prepared crude product through a silica gel column, and performing gradient elution through methanol and dichloromethane.
5. The method for preparing the hypoxic-responsive liposome according to claim 3, wherein the polymerization degree of the polyethylene glycol is 25 to 30.
6. The method for preparing hypoxic-responsive liposome according to claim 3, wherein the polyethylene glycol-azobenzene is synthesized in the following manner: dissolving polyethylene glycol and azobenzene in a mixed solution of dichloromethane and trichloromethane, adding a catalyst and a dehydrating agent, and stirring for reaction at room temperature.
7. The preparation method of the hypoxic-responsive liposome as claimed in claim 3, wherein in the polyethylene glycol-azobenzene-photosensitizer IR complex, the molar ratio of the polyethylene glycol, azobenzene and photosensitizer is 0.8-1.2: 5: 0.8 to 1.2;
or, the organic solvent is ethanol.
8. Use of the hypoxic responsive liposome of claim 1 in the preparation of targeted drug carriers.
9. The hypoxic-responsive liposome of claim 8, wherein the drug is used for treating a disease exhibiting a hypoxic state, and the drug is an anti-tumor drug or an anti-cardiovascular disease drug.
10. The hypoxic-responsive liposome of claim 9, wherein the drug is an anti-tumor drug, for use in the preparation of a targeted drug carrier.
CN202010676032.9A 2020-07-14 2020-07-14 Hypoxic response liposome and application thereof in preparation of antitumor drugs Active CN111773184B (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106822895A (en) * 2017-01-06 2017-06-13 深圳市前海安测信息技术有限公司 Photoresponse liposome and its preparation method and application
CN107281161A (en) * 2017-05-16 2017-10-24 浙江大学 A kind of medicament nano-preparation and preparation method thereof
CN107982533A (en) * 2017-11-14 2018-05-04 中国药科大学 The preparation and application of the light sensitizing type oxygen deprivation stress cation carrier of anti-protein adsorption
CN108653288A (en) * 2018-05-29 2018-10-16 福建医科大学孟超肝胆医院 A kind of weary oxygen responsive polymer nanoparticle and its application
CN110372829A (en) * 2019-07-19 2019-10-25 苏州大学 The preparation and application of the polymer gel fluorescence probe of azo-based reduction response

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106822895A (en) * 2017-01-06 2017-06-13 深圳市前海安测信息技术有限公司 Photoresponse liposome and its preparation method and application
CN107281161A (en) * 2017-05-16 2017-10-24 浙江大学 A kind of medicament nano-preparation and preparation method thereof
CN107982533A (en) * 2017-11-14 2018-05-04 中国药科大学 The preparation and application of the light sensitizing type oxygen deprivation stress cation carrier of anti-protein adsorption
CN108653288A (en) * 2018-05-29 2018-10-16 福建医科大学孟超肝胆医院 A kind of weary oxygen responsive polymer nanoparticle and its application
CN110372829A (en) * 2019-07-19 2019-10-25 苏州大学 The preparation and application of the polymer gel fluorescence probe of azo-based reduction response

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Multifunctional Micelles Dually Responsive to Hypoxia and Singlet Oxygen: Enhanced Photodynamic Therapy via Interactively Triggered Photosensitizer Delivery;Juanjuan Li et al;《ACS Applied Materials&Interfaces》;20180503;第10卷;17117-17128 *

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