CN112439080A - Magnetic bacterium for diagnosis and treatment and preparation method thereof - Google Patents
Magnetic bacterium for diagnosis and treatment and preparation method thereof Download PDFInfo
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Abstract
The invention provides a magnetic bacteria AMB-1-INPs for diagnosis and treatment and a preparation method thereof, which mark nano materials on magnetotactic bacteria biological carriers, and particularly relates to a nano fluorescence marking method of magnetotactic bacteria, which has strong specificity and is rapid, simple and convenient. The invention selects magnetotactic bacteria AMB-1 with high safety and strong targeting as a bacterial biological carrier, and chemically cross-links the magnetotactic bacteria AMB-1 rich in free-SH and phospholipid-polymer nano probes (INPs) loaded with ICG and provided with maleimide groups on the surface to construct the diagnosis and treatment magnetic bacteria AMB-1-INPs with fluorescence imaging capability. According to the method, the nano fluorescent probes INPs are stably marked on the surface of the magnetotactic bacteria AMB-1, the reaction efficiency of the nano probes and the surface of the bacteria can be prevented from being reduced due to cross-linking, the obtained magnetic bacteria AMB-1-INPs for diagnosis and treatment can deeply penetrate through the tumor under the control of an external magnetic field to perform fluorescent tracking, and the practical requirements of basic research and clinical real-time evaluation on the tumor treatment effect are met.
Description
Technical Field
The invention relates to the field of nano medicine, in particular to a diagnosis and treatment magnetic bacterium and a preparation method and application thereof.
Background
Over the past few decades, liposomes have been known for their good biocompatibility, low immunogenicity, high flexibility, controlled release kinetics, and drug loading (e.g., hydrophilic or hydrophobic drugs, imaging agents, chemotherapeutic agents, etc.). However, liposomes also have inevitable disadvantages, such as insufficient pharmacokinetics, poor local targeting (nonspecific biodistribution), lack of deep tissue penetration, etc., which limit their further clinical applications. In recent years, bacteria have been receiving attention from researchers due to their good tumor anaerobic targeting ability and ability to be autonomously driven, and have been shown to accumulate in tissues preferentially by anaerobic chemotaxis, including E.coli, magnetotactic bacteria and other genera, thus promising potential applications for bacterial-based therapeutics. Although bacteria can be used as therapeutics to address the above issues, they are not compatible with computer-based tumor area navigation, which is believed to be the most likely to enhance targeting. However, studies have shown that the magnetotactic property of magnetotactic bacterium AMB-1 can be combined with computer navigation to enhance its targeting property, and the penetration of flagella and external magnetic field control is deeply carried out on tumors, so that the problem is alleviated.
Magnetotactic bacteria AMB-1 is facultative microaerobic type microorganism, can form nanometer magnetic particles in vivo and can do directional movement under the action of an external magnetic field, which mainly lives in the aerobic-anaerobic transition zone in water and is able to find a region of a specific oxygen concentration in water efficiently and in time, therefore, the magnetic bacteria AMB-1 combined with the in vitro controllable magnetic field to realize the targeted delivery to the deep part of the anoxic tumor becomes the hot spot of the current research, such as the Thexin (magnetic bacterium AMB-1 magnetosome constructed magnetic targeting anticancer drug delivery system, the Master academic thesis of the university of Huaqiao, 2012) uses the separated and purified magnetosome in AMB-1 as a carrier, methotrexate is connected to magnetosomes through genipin to construct a magnetic targeting anticancer drug delivery system, and the system has the advantages of high drug loading rate, high encapsulation rate, slow release and directional drug delivery.
In the prior art, it has been reported that a nano material is added on the surface of bacteria to provide a protective layer for the bacteria, and a nano probe is prepared with aromatic, for example, CN200910188814 discloses a nano particle and a preparation method thereof, wherein a polylactic acid-glycolic acid copolymer (PLGA) is used to form an inner core, an intermediate layer formed by phospholipid surrounds the surface of the inner core, and a shell part formed by distearoyl phosphatidyl ethanolamine-polyethylene glycol containing amino or carboxyl is inserted in the intermediate layer. This document does not relate to the labeling of fluorescent probes and has a limited range of use. CN201010607708 discloses a fluorescent nanoprobe, which also has an inner core formed by polylactic acid-glycolic acid copolymer, a middle layer formed by phospholipid surrounding the surface of the inner core, and an outer shell portion formed by distearoyl phosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG) containing amino or carboxyl interspersed in the middle layer, wherein indocyanine green (ICG) is dispersed in the inner core. The two methods for preparing the nano particles in the prior art both adopt a stirring and mixing mode, so that the preparation efficiency is low, and the time consumption is long. CN201210424026 and CN201210574535 disclose two kinds of nano-drug particles and a preparation method thereof, which combine the advantages of a nano-encapsulation technology, a chemotherapeutic drug and a near-infrared photothermal conversion reagent for thermotherapy, and the two methods solve the technical problems of combined action of thermotherapy and chemotherapy, loading of the near-infrared photothermal conversion reagent and the chemotherapeutic drug at the same time, and slow release. None of the above prior art uses attenuated bacteria for targeted therapy of tumors, and even less magnetotactic bacteria AMB-1.
The aim of the present invention is to develop a new drug delivery strategy, a method of bacterial vector, while maintaining its deep targeting ability to solid tumors. The nano fluorescent probes INPs are efficiently and stably marked on the surface of the magnetotactic bacteria AMB-1 to prepare the magnetic bacteria AMB-1-INPs for diagnosis and treatment, and the magnetic probes can deeply penetrate through tumors under the control of an external magnetic field to perform fluorescent tracking, so that the treatment effect of the magnetic probes can be evaluated in real time, great convenience is provided for the development and clinical treatment of tumors and the research of related antitumor drugs, and the magnetic probes INPs have wide application prospects.
Disclosure of Invention
The invention provides a magnetic diagnosis and treatment bacterium, wherein the surface of the magnetic diagnosis and treatment bacterium is marked with nano fluorescent probes (INPs), and the INPs are chemically cross-linked through maleimide groups on the surface and thiol groups on the surface of magnetotactic bacteria treated by a reducing agent; the INPs comprise amphoteric compounds, monolayer lipid molecules, near-infrared photothermal conversion reagents and hydrophobic polymers; the amphoteric compound contains a maleimide group; the bacteria are magnetotactic bacteria.
The invention also provides a method for marking magnetic bacteria for diagnosis and treatment by the nano fluorescent probe, which is strong in specificity, rapid, simple and convenient, and comprises the step of chemically crosslinking maleimide groups on the surface of the nano fluorescent probe (INPs) and thiol groups on the surface of the magnetotactic bacteria treated by a reducing agent, wherein the INPs comprise a hydrophilic outer shell, an intermediate layer and a hydrophobic inner shell, the hydrophilic outer shell contains an amphoteric compound, the intermediate layer contains a single-layer lipid molecule, and the hydrophobic inner shell contains a near-infrared photothermal conversion reagent and a hydrophobic polymer; the amphoteric compound is inserted into the middle layer to form a hydrophobic shell; the near-infrared photothermal conversion reagent is adsorbed on the hydrophobic polymer to form a hydrophobic inner shell.
Preferably, the amphoteric compound is distearoyl phosphatidyl ethanolamine-carboxy polyethylene glycol (DSPE-PEG) or distearoyl phosphatidyl ethanolamine-polyethylene glycol-maleic amide (DSPE-PEG-Mal), preferably DSPE-PEG-Mal; preferably, the monolayer lipid molecules comprises lecithin or cephalin, preferably vegetable lecithin, and more preferably soy lecithin.
Preferably, the outer shell comprises soybean lecithin and DSPE-PEG-Mal in a mass ratio of 2: 3.
preferably, the near-infrared photothermal conversion reagent comprises one or more of indocyanine green (ICG), gold nanorods and carbon nanotubes, preferably ICG; preferably, the hydrophobic polymer is selected from polylactic-co-glycolic acid (PLGA), polylactic acid, polycaprolactone, preferably PLGA.
Preferably, the INPs further comprise chemotherapeutic agents adsorbed to the lipid ends and monolayer lipid molecules of the amphipathic compounds; preferably, the chemotherapeutic drug comprises one or more of adriamycin, epirubicin, paclitaxel, catharanthine and platinum drugs.
Preferably, the magnetic bacteria for diagnosis and treatment are magnetotactic bacteria AMB-1 strain; preferably, the reducing agent is tris (2-carboxyethyl) phosphine (TCEP).
The invention also provides a preparation method of INPs, which comprises the following steps:
(1) mixing soybean lecithin ethanol solution and DSPE-PEG-Mal ethanol solution at a ratio of 2: 3, the total weight of the lecithin and the DSPE-PEG-Mal is 15 percent of the total weight of the PLGA;
(2) adding ICG 4% ethanol solution into 2mL 4% ethanol solution;
(3) mixing the solutions in the steps (1) and (2) to obtain a mixed solution, and ultrasonically dispersing the mixed solution for 5 minutes by using an ultrasonic crusher;
(4) in the ultrasonic process of the step (3), dropwise adding a PLGA acetone solution into the mixed solution to form a nano probe dispersion liquid;
(5) and (5) transferring the nano probe dispersion liquid obtained in the step (4) into a 3500KDa dialysis bag for dialysis and concentration to obtain purified INPs.
The invention also provides a preparation method of the diagnosis and treatment magnetic bacteria, which comprises the following steps:
(1) preparing INPs by the method;
(2) will have a density of 107-108Collecting the CFU/mL magnetotactic bacteria in a centrifuge tube, and centrifuging under 3500rpm gravity;
(3) resuspending magnetotactic bacteria in 20-30mM TCEP in PBS and incubating at 37 deg.C for 20-120 min;
(4) the bacteria were washed twice with PBS;
(5) adding 1mL of INPs prepared in the step (1) into the magnetotactic bacteria obtained in the step (4), and incubating at 37 ℃ for 20-120 minutes;
(6) and (4) centrifugally washing to obtain the diagnosis and treatment magnetic bacteria marked by the nano fluorescent probe.
The invention also provides magnetic bacteria AMB-1-INPs for diagnosis and treatment marked by the nano fluorescent probe prepared by any one of the methods.
The invention also provides application of the magnetotactic bacteria or the diagnosis and treatment magnetic bacteria AMB-1-INPs in preparation or screening of drugs for treating and/or preventing tumors.
The technical principle and the beneficial effects of the invention are as follows:
the aim of the present invention is to develop a new drug delivery strategy, namely a method for bacterial vectors, while maintaining their deep targeting ability for solid tumors, while enabling efficient fluorescent tracing of artificial magnetotactic bacterial vectors. The invention selects magnetotactic bacteria AMB-1 with high safety and strong targeting as a bacterial biological carrier, and adopts a reducing agent tris (2-carboxyethyl) phosphine (TCEP) to mildly reduce disulfide bonds (S-S) on the outer membrane protein surface of the magnetotactic bacteria AMB-1 into Sulfydryl (SH); then, chemically crosslinking magnetotactic bacteria AMB-1 rich in free-SH and phospholipid-polymer nanoprobes (INPs) loaded with near-infrared fluorescent dye ICG and provided with maleimide groups (Mal) on the surface to construct AMB-1-INPs with fluorescence imaging capability. The method is rapid, simple, safe and efficient, the nano fluorescent probes INPs are stably marked on the surface of the magnetotactic bacteria AMB-1, the reaction efficiency of the nano probes and the surface of the bacteria can be prevented from being reduced due to cross-linking, and the prepared magnetic diagnosis and treatment bacteria AMB-1-INPs can meet the practical requirements of basic research and clinical application on tracking, monitoring bacteria and real-time evaluation of tumor treatment effects.
Drawings
FIG. 1 is SEM images of magnetotactic bacteria AMB-1 and therapeutic magnetic bacteria AMB-1-INPs.
FIG. 2 is a hysteresis loop curve (A) of magnetotactic bacteria AMB-1 and diagnostic magnetic bacteria AMB-1-INPs, and an aggregation condition (B) of diagnostic magnetic bacteria AMB-1-INPs after an external magnetic field acts for 15 min.
Detailed Description
The present invention will be described in further detail with reference to specific examples below so that those skilled in the art can better understand the present invention and practice the present invention, but the examples are not intended to limit the present invention.
The experimental procedures used in the following examples are conventional unless otherwise specified. The materials, reagents and the like used are commercially available unless otherwise specified.
Example 1
INPs were prepared by one-step ultrasound. First, an ethanol solution of soybean lecithin (10mg/mL, 12. mu.L) and an ethanol solution of DSPE-PEG-Mal (10mg/mL, 18. mu.L) were mixed at a ratio of 2: 3 (total weight of lecithin and DSPE-PEG-Mal is 15% of total weight of PLGA), ICG 4% ethanol solution (1mg/mL, 1mL) was added to 2mL 4% ethanol solution. Then, the above mixed solution was ultrasonically dispersed for 5 minutes at a frequency of 20kHz and a power of 130W using a VCX130 ultrasonicator, and a PLGA acetone solution (4mg/mL, 0.5mL) was dropwise added to the above mixed solution during the ultrasonic process to form a microprobe dispersion. And finally, transferring the nano probe dispersion liquid into a 3500KDa dialysis bag for dialysis and concentration to obtain purified INPs.
Will have a density of 108CFU/mL magnetotactic bacteria AMB-1 were collected in centrifuge tubes, centrifuged at 3500rpm under gravity, and resuspended in 30mM TCEP in PBS. The bacteria were then incubated at 37 ℃ for 20 minutes and washed twice with PBS. 1mL of INPs at a concentration of 100mg/mL were then added to 108And (3) incubating the bacteria in the CFU/mL for 2 hours at 37 ℃, and centrifuging and washing to obtain the magnetic micro-robot AMB-1-INPs marked by the nano fluorescent probe.
Example 2
INPs were prepared by one-step ultrasound. First, an ethanol solution of soybean lecithin (10mg/mL, 12. mu.L) and an ethanol solution of DSPE-PEG-Mal (10mg/mL, 18. mu.L) were mixed at a ratio of 2: 3 (total weight of lecithin and DSPE-PEG-Mal is 15% of total weight of PLGA), ICG 4% ethanol solution (0.9mg/mL, 1mL) was added to 2mL 4% ethanol solution. Then, the above mixed solution was ultrasonically dispersed for 5 minutes at a frequency of 20kHz and a power of 130W using a VCX130 ultrasonicator, and a PLGA acetone solution (4mg/mL, 0.5mL) was dropwise added to the above mixed solution during the ultrasonic process to form a microprobe dispersion. And finally, transferring the nano probe dispersion liquid into a 3500KDa dialysis bag for dialysis and concentration to obtain purified INPs.
Will have a density of 107CFU/mL magnetotactic bacteria AMB-1 were collected in centrifuge tubes, centrifuged at 3500rpm under gravity, and resuspended in 30mM TCEP in PBS. The bacteria were then incubated at 37 ℃ for 30 minutes and washed twice with PBS. 1mL of INPs at a concentration of 50mg/mL were then added to 107And (3) incubating the bacteria in the CFU/mL for 2 hours at 37 ℃, and centrifuging and washing to obtain the magnetic micro-robot AMB-1-INPs marked by the nano fluorescent probe.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (10)
1. The magnetic diagnosis and treatment bacteria have nano fluorescent probes (INPs) marked on the surface, wherein the INPs are chemically cross-linked through maleimide groups on the surface and thiol groups on the surface of magnetotactic bacteria treated by a reducing agent; the INPs comprise amphoteric compounds, monolayer lipid molecules, near-infrared photothermal conversion reagents and hydrophobic polymers; the amphoteric compound contains a maleimide group.
2. A method for labeling magnetotactic bacteria by using nano fluorescent probes comprises the steps of chemically crosslinking maleimide groups on the surfaces of the nano fluorescent probes (INPs) with thiol groups on the surfaces of the magnetotactic bacteria after being treated by a reducing agent, wherein the INPs comprise hydrophilic outer shells, middle layers and hydrophobic inner shells, the hydrophilic outer shells contain amphoteric compounds, the amphoteric compounds contain the maleimide groups, the middle layers contain monolayer lipid molecules, and the hydrophobic inner shells contain near-infrared photothermal conversion reagents and hydrophobic polymers; the amphoteric compound is inserted into the middle layer to form a hydrophobic shell; the near-infrared photothermal conversion reagent is adsorbed on the hydrophobic polymer to form a hydrophobic inner shell.
3. The theranostic magnetic bacterium according to claim 1 or the method according to claim 2, the amphoteric compound is distearoylphosphatidylethanolamine-carboxypolyethylene glycol (DSPE-PEG) or distearoylphosphatidylethanolamine-polyethylene glycol-maleamide (DSPE-PEG-Mal), preferably DSPE-PEG-Mal; the monolayer lipid molecules comprise lecithin or cephalin, preferably vegetable lecithin, and more preferably soybean lecithin.
4. The theranostic magnetic bacterium of claim 1 or the method of claim 2, wherein the near-infrared photothermal conversion reagent comprises any one or more of indocyanine green (ICG), gold nanorods, carbon nanotubes, preferably ICG; the hydrophobic polymer is selected from polylactic-co-glycolic acid (PLGA), polylactic acid, polycaprolactone, preferably PLGA.
5. The method of claim 2 or the diagnostic magnetic bacteria of claim 1, wherein said INPs further comprise chemotherapeutic agents adsorbed to the lipid-terminal and monolayer lipid molecules of said amphipathic compounds, said chemotherapeutic agents comprising one or more of doxorubicin, epirubicin, paclitaxel, catharanthine, and platinum-based drugs.
6. The theranostic magnetic bacterium of claim 1 or the method of claim 2, the theranostic magnetic bacterium being a magnetotactic bacterium AMB-1 strain; the reducing agent is tris (2-carboxyethyl) phosphine (TCEP).
7. A method for preparing nanometer fluorescent probes (INPs) comprises the following steps:
(1) mixing soybean lecithin ethanol solution and DSPE-PEG-Mal ethanol solution at a ratio of 2: 3, the total weight of the lecithin and the DSPE-PEG-Mal is 15 percent of the total weight of the PLGA;
(2) adding ICG 4% ethanol solution into 2mL 4% ethanol solution;
(3) mixing the solutions in the steps (1) and (2) to obtain a mixed solution, and ultrasonically dispersing the mixed solution for 5 minutes by using an ultrasonic crusher;
(4) in the ultrasonic process of the step (3), dropwise adding a PLGA acetone solution into the mixed solution to form a nano probe dispersion liquid;
(5) and (5) transferring the nano probe dispersion liquid obtained in the step (4) into a 3500KDa dialysis bag for dialysis and concentration to obtain purified INPs.
8. A method for preparing magnetic bacteria for diagnosis and treatment comprises the following steps:
(1) preparing INPs according to the method of claim 7;
(2) will have a density of 107-108Collecting the CFU/mL magnetotactic bacteria in a centrifuge tube, and centrifuging under 3500rpm gravity;
(3) resuspending magnetotactic bacteria in 20-30mM TCEP in PBS and incubating at 37 deg.C for 20-120 min;
(4) the bacteria were washed twice with PBS;
(5) adding 1mL of INPs prepared in the step (1) into the magnetotactic bacteria obtained in the step (4), and incubating at 37 ℃ for 20-120 minutes;
(6) centrifugally washing to obtain the diagnosis and treatment magnetic bacteria marked by the nano fluorescent probe; the magnetotactic bacteria is AMB-1.
9. The nano fluorescent probe-labeled magnetotactic bacterium prepared according to any one of claims 2 to 6 or the magnetic diagnostic bacterium prepared according to the method of claim 8, wherein the magnetotactic bacterium is AMB-1.
10. Use of a magnetotactic bacterium labeled with a nano fluorescent probe prepared according to any one of claims 2 to 6, or a magnetic diagnostic bacterium prepared according to the method of claim 8, or a magnetic diagnostic bacterium according to claim 1 in the preparation or screening of a drug for treating and/or preventing tumors.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113018462A (en) * | 2021-03-22 | 2021-06-25 | 中国科学院化学研究所 | Preparation method and application of efficient tumor targeting T1-T2 dual-mode imaging contrast agent based on magnetotactic bacteria |
| CN116271084A (en) * | 2023-01-04 | 2023-06-23 | 深圳市第二人民医院 | Drug magnetic delivery system based on magnetotactic bacteria, and preparation method and application thereof |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1927400A (en) * | 2006-09-25 | 2007-03-14 | 唐喜庆 | Biomagnetism nano target anti-cancer drug and its preparation |
| US20100135912A1 (en) * | 2008-12-02 | 2010-06-03 | Gambhir Sanjiv S | Magnetotactic bacteria mri positive contrast enhancement agent and methods of use |
| CN102533248A (en) * | 2010-12-27 | 2012-07-04 | 中国科学院深圳先进技术研究院 | Fluorescence nanometer probe and preparation method thereof |
| CN103040757A (en) * | 2012-12-26 | 2013-04-17 | 深圳先进技术研究院 | Core-shell drug nano-particles, as well as preparation method and application thereof |
| CN103099784A (en) * | 2012-10-29 | 2013-05-15 | 深圳先进技术研究院 | Nanometer medicine particle, preparation method and application thereof |
| US20130209368A1 (en) * | 2010-09-09 | 2013-08-15 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd | Near infrared fluorescent particles and uses thereof |
| CN105018401A (en) * | 2015-07-09 | 2015-11-04 | 中国科学院深圳先进技术研究院 | Artificial magnetotactic bacterium for targeted therapy and construction method and application thereof |
| CN105193733A (en) * | 2014-06-09 | 2015-12-30 | 东北林业大学 | Medicine slow-release nanoparticle wrapping magnetosomes of magnetotactic bacteria and preparation method of medicine slow-release nanoparticle |
| CN108096214A (en) * | 2017-12-26 | 2018-06-01 | 曲阜师范大学 | A kind of magnetotactic bacteria quantum dot microcapsules and preparation method thereof |
-
2019
- 2019-08-30 CN CN201910814388.1A patent/CN112439080B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1927400A (en) * | 2006-09-25 | 2007-03-14 | 唐喜庆 | Biomagnetism nano target anti-cancer drug and its preparation |
| US20100135912A1 (en) * | 2008-12-02 | 2010-06-03 | Gambhir Sanjiv S | Magnetotactic bacteria mri positive contrast enhancement agent and methods of use |
| US20130209368A1 (en) * | 2010-09-09 | 2013-08-15 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd | Near infrared fluorescent particles and uses thereof |
| CN102533248A (en) * | 2010-12-27 | 2012-07-04 | 中国科学院深圳先进技术研究院 | Fluorescence nanometer probe and preparation method thereof |
| CN103099784A (en) * | 2012-10-29 | 2013-05-15 | 深圳先进技术研究院 | Nanometer medicine particle, preparation method and application thereof |
| CN103040757A (en) * | 2012-12-26 | 2013-04-17 | 深圳先进技术研究院 | Core-shell drug nano-particles, as well as preparation method and application thereof |
| CN105193733A (en) * | 2014-06-09 | 2015-12-30 | 东北林业大学 | Medicine slow-release nanoparticle wrapping magnetosomes of magnetotactic bacteria and preparation method of medicine slow-release nanoparticle |
| CN105018401A (en) * | 2015-07-09 | 2015-11-04 | 中国科学院深圳先进技术研究院 | Artificial magnetotactic bacterium for targeted therapy and construction method and application thereof |
| CN108096214A (en) * | 2017-12-26 | 2018-06-01 | 曲阜师范大学 | A kind of magnetotactic bacteria quantum dot microcapsules and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| FUMING CHEN 等: ""Nanophotosensitizer-engineered Salmonella bacteria with hypoxia targeting and photothermal-assisted mutual bioaccumulation for solid tumor therapy"", 《BIOMATERIALS》 * |
| FUMING CHEN 等: ""Nanophotosensitizer-engineered Salmonella bacteria with hypoxia targeting and photothermal-assisted mutual bioaccumulation for solid tumor therapy"", 《BIOMATERIALS》, vol. 214, 24 May 2019 (2019-05-24), pages 2 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113018462A (en) * | 2021-03-22 | 2021-06-25 | 中国科学院化学研究所 | Preparation method and application of efficient tumor targeting T1-T2 dual-mode imaging contrast agent based on magnetotactic bacteria |
| CN113018462B (en) * | 2021-03-22 | 2021-12-14 | 中国科学院化学研究所 | Preparation method and application of efficient tumor targeting T1-T2 dual-mode imaging contrast agent based on magnetotactic bacteria |
| CN116271084A (en) * | 2023-01-04 | 2023-06-23 | 深圳市第二人民医院 | Drug magnetic delivery system based on magnetotactic bacteria, and preparation method and application thereof |
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