CN112755184A - Tumor targeting carrier for low-dose radiotherapy, preparation method thereof and tumor targeting drug - Google Patents

Tumor targeting carrier for low-dose radiotherapy, preparation method thereof and tumor targeting drug Download PDF

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CN112755184A
CN112755184A CN202011354250.7A CN202011354250A CN112755184A CN 112755184 A CN112755184 A CN 112755184A CN 202011354250 A CN202011354250 A CN 202011354250A CN 112755184 A CN112755184 A CN 112755184A
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张晗
朵燕红
张家宜
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Shenzhen University
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Abstract

The invention provides a tumor targeting vector for low-dose radiotherapy, which comprises anaerobic bacteria and black phosphorus quantum dots adsorbed on the anaerobic bacteria. The invention also provides a preparation method of the tumor targeting vector for low-dose radiotherapy and a medicament for low-dose radiotherapy. The tumor targeting vector for low-dose radiotherapy has anaerobic bacteria, and can be accurately positioned to tumor cells by virtue of the anaerobic tropism of the anaerobic bacteria. The tumor targeting vector for low-dose radiotherapy adopts the Black Phosphorus Quantum Dots (BPQD), has high photo-thermal conversion efficiency, and achieves the effect of targeted therapy of hypoxic tumor cells through the photo-thermal effect. On the other hand, the Black Phosphorus Quantum Dots (BPQD) also have the sensitization effect of radiotherapy, and the two are synergistic, so that the curative effect of radiotherapy can be obviously improved, the tumor can be treated at low dose, and the clinical application potential is huge.

Description

Tumor targeting carrier for low-dose radiotherapy, preparation method thereof and tumor targeting drug
Technical Field
The invention relates to the technical field of anti-tumor biological nano-medicines, in particular to a tumor targeting carrier for low-dose radiotherapy, and also relates to a preparation method of the tumor targeting carrier for low-dose radiotherapy, and a tumor targeting medicament comprising the tumor targeting carrier for low-dose radiotherapy.
Background
Radiation Therapy (RT) is one of the three main approaches used to treat cancer, and relies on targeted delivery of high-energy X-rays or gamma rays, inducing DNA damage and apoptosis of tumor cells, thereby promoting tumor ablation. Although RT is a common treatment modality, it is associated with serious side effects, the efficacy of which may be limited by oxygen deficiency within the Tumor Microenvironment (TME), leading to failure to completely eradicate the target tumor. Many clinical trials are currently attempting to overcome the oxygen dependence of RT by hyperbaric oxygen therapy (HBO) to improve the therapeutic effect of RT. However, HBO also has serious side effects including barotrauma and hyperoxic seizures, etc., and thus the method is not very practical. Recent studies have reported the intracellular production of O in tumor cells2Of (2) a process comprising decomposing H2O2Production of O2But also suffers from low levels of tumor endogenous hydrogen peroxide (1)<50 μ M). Therefore, there is an urgent need to develop a new radiosensitizing therapy that can specifically target hypoxic tumor tissues and make them more sensitive to RT, thereby facilitating tumor ablation.
Disclosure of Invention
In view of the above, the present invention provides a tumor targeting vector for low-dose radiotherapy, a preparation method of the tumor targeting vector for low-dose radiotherapy, and a medicament for low-dose radiotherapy, so as to solve the defects of poor tumor targeting, low tumor cell reflex sensitivity and the like of the existing radiotherapy.
In a first aspect, the invention provides a tumor targeting vector for low-dose radiotherapy, which comprises anaerobic bacteria and black phosphorus quantum dots adsorbed on the anaerobic bacteria.
Preferably, the anaerobic bacteria is escherichia coli or salmonella.
The tumor targeting vector for low-dose radiotherapy comprises anaerobic bacteria and black phosphorus quantum dots adsorbed on the anaerobic bacteria. The tumor targeting carrier for low-dose radiotherapy adopts biocompatible materials, and has no side effect on human body. The tumor targeting vector for low-dose radiotherapy has anaerobic bacteria, and can be accurately positioned to tumor cells by virtue of the anaerobic tropism of the anaerobic bacteria. The tumor targeting vector for low-dose radiotherapy adopts the Black Phosphorus Quantum Dots (BPQD), has high photo-thermal conversion efficiency, and achieves the effect of targeted therapy of hypoxic tumor cells through the photo-thermal effect. On the other hand, the Black Phosphorus Quantum Dots (BPQD) also have the sensitization effect of radiotherapy, and the two are synergistic, so that the curative effect of radiotherapy can be obviously improved, the tumor can be treated at low dose, and the clinical application potential is huge.
In a second aspect, the present invention also provides a method for preparing a tumor targeting vector for low-dose radiotherapy, comprising the following steps:
providing anaerobic bacteria and black phosphorus quantum dots, carrying out surface ammoniation treatment on the anaerobic bacteria, mixing the anaerobic bacteria subjected to surface ammoniation treatment with the black phosphorus quantum dots to enable the black phosphorus quantum dots to be adsorbed on the anaerobic bacteria, and preparing the tumor targeting carrier for low-dose radiotherapy.
The preparation method of the tumor targeting vector for low-dose radiotherapy has the advantages of simple steps, low cost, suitability for large-scale industrial production and the like.
Preferably, the preparation method of the black phosphorus quantum dot comprises the following steps: providing black phosphorus powder, dissolving the black phosphorus powder in N-methyl pyrrolidone, sequentially carrying out probe ultrasonic treatment and water bath ultrasonic treatment on an N-methyl pyrrolidone dispersion system of the black phosphorus powder, firstly carrying out primary centrifugation on the dispersion system subjected to the water bath ultrasonic treatment to collect supernatant, and then carrying out secondary centrifugation on the supernatant to collect precipitate, thereby obtaining the black phosphorus quantum dot.
Preferably, the concentration of black phosphorus in the N-methylpyrrolidone dispersion of black phosphorus powder is 0.25 to 5 mg/ml.
Preferably, the power of the probe ultrasonic wave is 600-2400W, the time of the probe ultrasonic wave is 1-5 h, and the frequency of the probe ultrasonic wave is 19-25 kHz;
the probe ultrasound is pulse probe ultrasound, and the pulse probe ultrasound is set to work for 2s at an interval of 4 s.
Preferably, the power of the water bath ultrasound is 150-500W, the time of the water bath ultrasound is 5-20 h, and the temperature of the water bath ultrasound is below 4 ℃.
Preferably, the rotating speed of the primary centrifugation is 5000-8000 rpm, the time of the primary centrifugation is 10-30 min, the rotating speed of the secondary centrifugation is 10000-15000 rpm, and the time of the secondary centrifugation is 10-30 min.
Preferably, the specific method of the ammoniation treatment is as follows: providing ammoniation reagent and PBS solution of anaerobic bacteria, uniformly mixing the ammoniation reagent and the PBS solution of the anaerobic bacteria, and centrifuging to prepare the anaerobic bacteria with ammoniated surfaces;
the ammoniation reagent is DSPE-PEG-NH2Or DSPE-PEG-Cy 5.
Preferably, the PEG has an average molecular weight of 2000.
Preferably, the mass-volume ratio of the ammoniation reagent to the PBS solution of the anaerobic bacteria is 0.1-5 mg/ml, and the concentration of the anaerobic bacteria in the PBS solution of the anaerobic bacteria is 106～108CFU/ml。
Preferably, the anaerobic bacteria subjected to surface ammoniation treatment and the black phosphorus quantum dots are uniformly stirred and mixed for 20-60 min, and the stirring revolution is 100-500 rpm.
Preferably, after the anaerobic bacteria subjected to surface ammoniation treatment and the black phosphorus quantum dots are uniformly stirred and mixed, the mixture is centrifuged at 3500-7500 rpm for 2-10 min, and the precipitate is the tumor targeting carrier for low-dose radiotherapy.
In a third aspect, the present invention also provides a medicament for low-dose radiation therapy, comprising the tumor targeting vector for low-dose radiation therapy according to the first aspect of the present invention.
The medicine for low-dose radiotherapy comprises a tumor targeting carrier for low-dose radiotherapy, has the effects of tumor photothermal therapy and photodynamic therapy, and can enhance the sensitivity of reflex therapy and improve the curative effect of the reflex therapy.
Advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of embodiments of the invention.
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In order to more clearly illustrate the contents of the present invention, a detailed description thereof will be given below with reference to the accompanying drawings and specific embodiments.
FIG. 1 is a flow chart of the preparation of tumor targeting vectors for low dose radiation therapy according to one embodiment of the present invention;
FIG. 2 is a graph of the results of a light test provided by the present invention;
FIG. 3 is a graph showing the results of a cell viability assay provided by the present invention;
FIG. 4 is a graph showing the results of a cell viability assay under low-oxygen ambient light;
FIG. 5 is a graph showing the results of cell viability assays in an normoxic environment under photothermal and low dose radiation conditions;
FIG. 6 is a graph showing the results of a cell viability assay in a hypoxic environment under photothermal and low dose radiation conditions.
Detailed Description
While the following is a description of the preferred embodiments of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention.
In a first aspect, the invention provides a tumor targeting vector for low-dose radiotherapy, which comprises anaerobic bacteria and black phosphorus quantum dots adsorbed on the anaerobic bacteria.
Preferably, the anaerobic bacteria is escherichia coli or salmonella.
In a second aspect, the present invention also provides a method for preparing a tumor targeting vector for low-dose radiotherapy, comprising the following steps:
providing anaerobic bacteria and black phosphorus quantum dots, carrying out surface ammoniation treatment on the anaerobic bacteria, mixing the anaerobic bacteria subjected to surface ammoniation treatment with the black phosphorus quantum dots to enable the black phosphorus quantum dots to be adsorbed on the anaerobic bacteria, and preparing the tumor targeting carrier for low-dose radiotherapy.
Preferably, the preparation method of the black phosphorus quantum dot comprises the following steps: providing black phosphorus powder, dissolving the black phosphorus powder in N-methyl pyrrolidone, sequentially carrying out probe ultrasonic treatment and water bath ultrasonic treatment on an N-methyl pyrrolidone dispersion system of the black phosphorus powder, firstly carrying out primary centrifugation on the dispersion system subjected to the water bath ultrasonic treatment to collect supernatant, and then carrying out secondary centrifugation on the supernatant to collect precipitate, thereby obtaining the black phosphorus quantum dot.
Preferably, the concentration of black phosphorus in the N-methylpyrrolidone dispersion of black phosphorus powder is 0.25 to 5 mg/ml.
Preferably, the power of the probe ultrasonic wave is 600-2400W, the time of the probe ultrasonic wave is 1-5 h, and the frequency of the probe ultrasonic wave is 19-25 kHz;
the probe ultrasound is pulse probe ultrasound, and the pulse probe ultrasound is set to work for 2s at an interval of 4 s.
Preferably, the power of the water bath ultrasound is 150-500W, the time of the water bath ultrasound is 5-20 h, and the temperature of the water bath ultrasound is below 4 ℃.
Preferably, the rotating speed of the primary centrifugation is 5000-8000 rpm, the time of the primary centrifugation is 10-30 min, the rotating speed of the secondary centrifugation is 10000-15000 rpm, and the time of the secondary centrifugation is 10-30 min.
Preferably, the specific method of the ammoniation treatment is as follows: providing ammoniation reagent and PBS solution of anaerobic bacteria, uniformly mixing the ammoniation reagent and the PBS solution of the anaerobic bacteria, and centrifuging to prepare the anaerobic bacteria with ammoniated surfaces;
the ammoniation reagent is DSPE-PEG-NH2Or DSPE-PEG-Cy 5.
Preferably, the PEG has an average molecular weight of 2000.
Preferably, the mass-volume ratio of the ammoniation reagent to the PBS solution of the anaerobic bacteria is 0.1-5 mg/ml, and the P of the anaerobic bacteriaThe concentration of anaerobic bacteria in the BS solution is 106～108CFU/ml。
Preferably, the anaerobic bacteria subjected to surface ammoniation treatment and the black phosphorus quantum dots are uniformly stirred and mixed for 20-60 min, and the stirring revolution is 100-500 rpm.
Preferably, after the anaerobic bacteria subjected to surface ammoniation treatment and the black phosphorus quantum dots are uniformly stirred and mixed, the mixture is centrifuged at 3500-7500 rpm for 2-10 min, and the precipitate is the tumor targeting carrier for low-dose radiotherapy.
In a third aspect, the present invention also provides a medicament for low-dose radiation therapy, comprising the tumor targeting vector for low-dose radiation therapy according to the first aspect of the present invention.
The following examples are provided to illustrate the preparation of tumor targeting vectors for low-dose radiotherapy and the prepared tumor targeting vectors for low-dose radiotherapy.
Example 1
As shown in fig. 1, the preparation method of the tumor targeting vector for low-dose radiotherapy comprises the following steps:
(1) preparation of Black phosphorus Quantum dots by ultrasonic peeling (BPQD)
25mg of BP powder was added to a 50ml sealed conical tube containing 25ml of NMP (N-methylpyrrolidone) and sonicated with a pulse probe at a power of 1200W for 3h with the sonication frequency set to 22kHz and the pulses of the pulsed probe sonication set to work for 2s with an interval of 4 s. After the probe ultrasound is finished, transferring the dispersion system subjected to the pulse probe ultrasound into water bath ultrasound to continue the ultrasound dispersion, wherein the power of the water bath ultrasound is 300W, the time of the water bath ultrasound is 10h, and the temperature of the water bath ultrasound is kept below 4 ℃. The dispersion after the two-step ultrasonic dispersion was centrifuged at 7000 rpm for 20 minutes, and the supernatant containing the Black Phosphorus Quantum Dots (BPQDs) was decanted. Then, the supernatant containing the Black Phosphorus Quantum Dots (BPQDs) was further centrifuged at 12000rpm for 20 minutes to obtain the Black Phosphorus Quantum Dots (BPQDs).
(2) Carrying out surface ammoniation treatment on anaerobic bacteria
1ml of a solution containing E.coli (1X 10)7CFU/mL) in PBS with 0.5mg DSPE-PEG-NH2Stirring and shaking at 37 deg.C for 30min, the average molecular weight of PEG was 2000, and the stirring speed was 200 rpm. After the mixture is evenly mixed by oscillation, the mixture is centrifuged to collect the sediment, the centrifugation revolution is 5000rpm, the centrifugation time is 3min, and the sediment is the amino modified anaerobic bacteria. The collected anaerobes were washed 3 more times with PBS and resuspended in 1ml PBS for further use.
(3) Preparing tumor targeting carrier
Adding 300 mu g of Black Phosphorus Quantum Dots (BPQD) into the 1ml of amino modified anaerobe PBS solution, stirring at 200rpm for 30min, uniformly stirring, centrifuging the mixed solution again, wherein the centrifugal rotation speed is 5000rpm, the centrifugation time is 3min, and collecting precipitates, namely the tumor targeting vector (BPQD-Esc, BE) for low-dose radiotherapy.
Example 2
The preparation method of the tumor targeting vector for low-dose radiotherapy comprises the following steps:
(1) preparation of Black phosphorus Quantum dots by ultrasonic peeling (BPQD)
6.25mg of BP powder was added to a 50ml sealed conical tube containing 25ml of NMP (N-methylpyrrolidone) and sonicated with a pulse probe at 2400W power for 1h, the sonication frequency was set to 25kHz, the pulses of the pulse probe sonication were set to work for 2s, with an interval of 4 s. After the probe ultrasound is finished, transferring the dispersion system subjected to the pulse probe ultrasound into water bath ultrasound to continue the ultrasound dispersion, wherein the power of the water bath ultrasound is 150W, the time of the water bath ultrasound is 20h, and the temperature of the water bath ultrasound is kept below 2 ℃. The dispersion after the two-step ultrasonic dispersion was centrifuged at 8000rpm for 10 minutes, and the supernatant containing the Black Phosphorus Quantum Dots (BPQD) was decanted. Then, the supernatant containing the Black Phosphorus Quantum Dots (BPQDs) was further centrifuged at 15000rpm for 10 minutes to obtain the Black Phosphorus Quantum Dots (BPQDs).
(2) Carrying out surface ammoniation treatment on anaerobic bacteria
1ml of a solution containing E.coli (1X 10)7CFU/mL) with 0.5mg of DSPE-PEG-Cy5 at 37 ℃ for 30 minutes with stirring and shaking, the average molecular weight of PEG was 2000 and the number of stirring revolutions was 200 rpm. After the mixture is evenly mixed by oscillation, the mixture is centrifuged to collect the sediment, the centrifugation revolution is 5000rpm, the centrifugation time is 3min,and precipitating to obtain the amino modified anaerobic bacteria. The collected anaerobes were washed 3 more times with PBS and resuspended in 1ml PBS for further use.
(3) Preparing tumor targeting carrier
And adding 100 mu g of Black Phosphorus Quantum Dots (BPQD) into the 1ml of amino-modified anaerobic bacteria PBS solution, stirring at 200rpm for 30min, uniformly stirring, centrifuging the mixed solution again, wherein the centrifugal rotation speed is 5000rpm, the centrifugation time is 3min, and collecting precipitates, namely the tumor targeting vector (BPQD-Esc, BE) for low-dose radiotherapy.
Example 3
(1) Preparation of Black phosphorus Quantum dots by ultrasonic peeling (BPQD)
125mg of BP powder was added to a 50ml sealed conical tube containing 25ml of NMP (N-methylpyrrolidone) and sonicated with a pulse probe at a power of 600W for 5h, the sonication frequency was set to 19kHz, the pulses of the pulse probe sonication were set to work for 2s, with an interval of 4 s. After the probe ultrasound is finished, transferring the dispersion system subjected to the pulse probe ultrasound into water bath ultrasound to continue the ultrasound dispersion, wherein the power of the water bath ultrasound is 500W, the time of the water bath ultrasound is 5h, and the temperature of the water bath ultrasound is kept below 0 ℃. The dispersion after the two-step ultrasonic dispersion was centrifuged at 5000rpm for 30 minutes, and the supernatant containing the Black Phosphorus Quantum Dots (BPQDs) was decanted. Then, the supernatant containing the Black Phosphorus Quantum Dots (BPQDs) was further centrifuged at 10000rpm for 30 minutes to obtain the Black Phosphorus Quantum Dots (BPQDs).
(2) Carrying out surface ammoniation treatment on anaerobic bacteria
1ml of the mixture containing Salmonella (1X 10)8CFU/mL) in PBS with 5mg DSPE-PEG-NH2Stirring and shaking at 37 deg.C for 60min, the average molecular weight of PEG was 2000, and the stirring speed was 400 rpm. After shaking and mixing uniformly, the mixed solution is centrifuged to collect precipitate, the centrifugation revolution is 3500rpm, the centrifugation time is 8min, and the precipitate is the amino modified anaerobic bacteria. The collected anaerobes were washed 3 more times with PBS and resuspended in 1ml PBS for further use.
(3) Preparing tumor targeting carrier
Adding 500 mu g of Black Phosphorus Quantum Dots (BPQD) into the 1ml of amino modified anaerobe PBS solution, stirring at 100rpm for 60min, uniformly stirring, centrifuging the mixed solution again, wherein the centrifugal speed is 5000rpm, the centrifugal time is 3min, and collecting precipitates, namely the tumor targeting vector (BPQD-Esc, BE) for low-dose radiotherapy.
Effect embodiment:
the performance test is carried out by adopting the black phosphorus quantum dot-escherichia coli tumor targeting vector (BE) prepared in the embodiment 1 of the invention, and then the effects of the vector and the medicament are verified.
(1) RT and laser therapy
Radiotherapy (RT) and laser irradiation tests were performed under hypoxic conditions, with the following six control groups: the first group, PBS + L, had only 808nm laser irradiation; second group, RT (2Gy), X-ray exposure of 2 Gy; the third group, BE, was treated with the tumor targeting vector for low dose radiation therapy prepared in example 1; the fourth group, BE + L, was treated with the tumor targeting vector for low dose radiotherapy prepared in example 1 in combination with 808nm laser irradiation; the fifth group, BE + RT, was treated with the tumor targeting vector for low dose radiotherapy prepared in example 1 in combination with 2Gy X-ray irradiation; the sixth group, BE + L + RT, was treated with the tumor targeting vector for low dose radiotherapy prepared in example 1 in combination with 808nm laser irradiation, 2Gy X-ray irradiation. In the specific test procedure, the cells in the first, fourth and sixth groups were exposed to 808nm laser radiation, and the cells in the second, fifth and sixth groups were exposed to 2Gy X-ray radiation for 10 minutes.
As a result, as shown in FIG. 2, the cells subjected to BE + L + RT (sixth group) treatment showed a significantly higher number of DSBs relative to the cells in the BE + RT (fifth group) and BE + L (fourth group) treated groups. On one hand, the photothermal action of BPQD can destroy the cellular DNA structure to trigger apoptosis, and on the other hand, BPQDs in BE also have radiotherapy sensitization, thereby forming more gamma-H2 AX focuses. gamma-H2 AX was 4.56-fold more in the BE + L + RT treated group relative to the single RT treated group, indicating that BE can act as a highly effective radiosensitizer under hypoxic conditions.
(2) Cell survival assay
FIG. 3 shows the results of cell survival tests under normoxic (21% oxygen content) conditions, and FIG. 4 shows the results of cell survival tests under hypoxic (2% oxygen content) conditions. The results of cell survival experiments showed that CT26 cells were very sensitive to radiotherapy under normoxic conditions, whereas the sensitizing effect of BE radiotherapy appeared to BE less pronounced (sensitization enhancement rate (SER) ═ 0.999). Under hypoxic conditions, CT26 cells were very insensitive to radiation therapy, and their survival rate was about 69% even under 6Gy of high intensity X-ray radiation. After the BE is added, the sensitization effect of radiotherapy is very obvious (SER is 1.17), and the survival rate of CT26 cells under 6Gy radiation is only 31 percent. This result indicates that BE has good sensitization ability in radiotherapy.
Fig. 5 shows the results of the cell survival test under the photothermal and low-dose radiation conditions in the normoxic environment, and fig. 6 shows the results of the cell survival test under the photothermal and low-dose radiation conditions in the hypoxic (anoxic) environment. Under the double treatment of photothermal and low-dose radiotherapy (2Gy), the growth of tumor cells under both hypoxia and normoxic conditions is significantly inhibited, and the number of clones is significantly reduced. The results of in vitro experiments fully prove that the BE prepared by the invention has the capability of effectively complementing photothermal and radiotherapy and can realize low-dose radiotherapy.
Coli are selectively accumulated and replicated in tumors due to their low oxygen tropism, and E.coli in the BE of the present invention is not destroyed, so that the BE prepared in the present invention has good tumor targeting ability.
The present invention also evaluates the antitumor activity of BE in vivo. Mice bearing CT26 tumors were randomized into six different treatment groups: (1) PBS + L group, (2) RT group, (3) BE + L group, (4) BE + RT group, (5) BPQD + L + RT group, and (6) BE + L + RT group. RT and L treatment alone was not sufficient to significantly inhibit tumor growth; in the BE + L and BE + RT groups, tumor growth was very significantly inhibited, consistent with the radiosensitizer and PTT activity of the preparations. And treatment with the BPQDs + L + RT group showed antitumor efficacy comparable to that observed with the BE + L and BE + RT groups. In the BE + L + RT treated group, maximal tumor growth arrest was observed in mice, consistent with the ability of BE to ablate tumor tissue efficiently. No significant body weight change was observed in the treated mice throughout the study, indicating that this treatment did not cause significant systemic toxicity. Accordingly, BE has high biocompatibility and promotes synergistic therapeutic effects of PTT and low-dose RT.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims (10)

1. A tumor targeting vector for low-dose radiotherapy is characterized by comprising anaerobic bacteria and black phosphorus quantum dots adsorbed on the anaerobic bacteria.
2. The tumor targeting vector for use in low dose radiation therapy according to claim 1, wherein said anaerobic bacteria is escherichia coli or salmonella.
3. A preparation method of a tumor targeting vector for low-dose radiotherapy is characterized by comprising the following steps:
providing anaerobic bacteria and black phosphorus quantum dots, carrying out surface ammoniation treatment on the anaerobic bacteria, mixing the anaerobic bacteria subjected to surface ammoniation treatment with the black phosphorus quantum dots to enable the black phosphorus quantum dots to be adsorbed on the anaerobic bacteria, and preparing the tumor targeting carrier for low-dose radiotherapy.
4. The method of claim 3, wherein the method of preparing the black phosphorus quantum dot comprises the following steps: providing black phosphorus powder, dissolving the black phosphorus powder in N-methyl pyrrolidone, sequentially carrying out probe ultrasonic treatment and water bath ultrasonic treatment on an N-methyl pyrrolidone dispersion system of the black phosphorus powder, firstly carrying out primary centrifugation on the dispersion system subjected to the water bath ultrasonic treatment to collect supernatant, and then carrying out secondary centrifugation on the supernatant to collect precipitate, thereby obtaining the black phosphorus quantum dot.
5. The method of claim 4, wherein the concentration of black phosphorus in the N-methylpyrrolidone dispersion of black phosphorus powder is 0.25-5 mg/ml.
6. The method for preparing a tumor targeting vector for low dose radiotherapy according to claim 4, wherein the power of the probe ultrasound is 600-2400W, the time of the probe ultrasound is 1-5 h, and the frequency of the probe ultrasound is 19-25 kHz;
the probe ultrasound is pulse probe ultrasound, and the pulse probe ultrasound is set to work for 2s at an interval of 4 s.
7. The method for preparing the tumor targeting vector for low-dose radiotherapy according to claim 4, wherein the power of the water bath ultrasound is 150-500W, the time of the water bath ultrasound is 5-20 h, and the temperature of the water bath ultrasound is below 4 ℃.
8. The method for preparing a tumor targeting vector for low dose radiation therapy according to claim 4, wherein the rotation speed of the primary centrifugation is 5000-8000 rpm, the time of the primary centrifugation is 10-30 min, the rotation speed of the secondary centrifugation is 10000-15000 rpm, and the time of the secondary centrifugation is 10-30 min.
9. The method for preparing a tumor targeting vector for low dose radiation therapy according to claim 3, wherein the specific method of ammoniation treatment is as follows: providing ammoniation reagent and PBS solution of anaerobic bacteria, uniformly mixing the ammoniation reagent and the PBS solution of the anaerobic bacteria, and centrifuging to prepare the anaerobic bacteria with ammoniated surfaces;
the ammoniaThe chemical reagent is DSPE-PEG-NH2Or DSPE-PEG-Cy 5.
10. A medicament for low dose radiation therapy comprising the tumor targeting vector for low dose radiation therapy of claim 1 or 2.
CN202011354250.7A 2020-11-26 2020-11-26 Tumor targeting carrier for low-dose radiotherapy, preparation method thereof and tumor targeting drug Pending CN112755184A (en)

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Cited By (3)

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CN113318229A (en) * 2021-06-01 2021-08-31 深圳大学 Anti-tumor preparation based on black arsenic-phosphorus nanosheets and preparation method thereof
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CN114657098A (en) * 2022-03-28 2022-06-24 深圳大学 Modified microorganism, modification method and application thereof, and antitumor drug
CN115282289A (en) * 2022-06-17 2022-11-04 深圳市人民医院 Tumor targeting carrier for low-dose radiotherapy, preparation method and medicine using same

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