CN113456841A - 188Re-labeled degradable nano probe for breast cancer diagnosis and treatment and preparation method thereof - Google Patents
188Re-labeled degradable nano probe for breast cancer diagnosis and treatment and preparation method thereof Download PDFInfo
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- CN113456841A CN113456841A CN202110765187.4A CN202110765187A CN113456841A CN 113456841 A CN113456841 A CN 113456841A CN 202110765187 A CN202110765187 A CN 202110765187A CN 113456841 A CN113456841 A CN 113456841A
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Abstract
The invention discloses188A Re-marked degradable nano probe for breast cancer diagnosis and treatment and a preparation method thereof,188the Re-marked degradable nano probe for breast cancer diagnosis and treatment comprises a nano probe which is composed of PLThe GA nano-particle entraps IDO inhibitor, and the nano-probe comprises the following components by molar mass: 4-6mol of lactide, 1-2mol of glycolide, an initiator, a surfactant, an IDO inhibitor and a dispersant, wherein the nanoprobe is connected with folic acid for targeting 4T1 breast cancer and connected with folic acid188Re is used for targeted tracking of breast cancer and lymph node metastasis, SPECT imaging and internal irradiation sensitivity increasing treatment, the degradable nanoprobe can achieve targeted tracking of breast cancer and lymph node metastasis, SPECT imaging and accurate internal irradiation sensitivity increasing treatment, and diagnosis and treatment integration of breast cancer is achieved.
Description
Technical Field
The invention relates to the technical field of tumor treatment, in particular to188Degradable Re-labeled breast cancer diagnosis and treatmentA nano probe and a preparation method.
Background
Breast cancer is a tumor in women with the first incidence and the second mortality, and seriously harms the life health and the quality of life of women. One of the main reasons for high mortality of breast cancer is that the early detection rate is low, and the diagnosis is often confirmed in the middle and late stages, so that the optimal treatment time is lost. Therefore, accurate diagnosis of early breast cancer is of great significance.
X-ray molybdenum targets, breast ultrasound and breast Magnetic Resonance (MRI) examination are the most common means for clinical diagnosis of breast cancer. However, these diagnostic methods have certain drawbacks, such as: the X-ray molybdenum target examination is difficult to detect the tiny tumor with deficient blood vessels and the tumor close to the chest wall; the ultrasonic inspection sensitivity is insufficient, and the requirement on experience is high; the detection rate of calcified lesions is low by MRI examination. If the breast cancer cannot be treated timely and effectively in early stage, the breast cancer is easy to deteriorate, and the breast cancer is dead. Lymph node metastasis is one of the most common signs of breast cancer deterioration, and studies have found that axillary lymph node-negative patients in the middle and later stages of breast cancer are only 20% -30%, while 10-year survival rate of lymph node metastasis-negative patients is much higher than that of lymph node metastasis patients. After the lymph node metastasis is positively diagnosed, axillary lymph node cleaning is clinically needed for a patient. Lymph node cleaning is often performed excessively in order to completely remove the remnants of tumor cells and prevent the recurrence of cancer. Excessive lymph node cleaning can lead to destruction of the immune system, causing problems such as lymph node reflux disorder, and often sequelae such as localized pain and related dysfunction. Studies have demonstrated that excessive lymph node dissection does not significantly prolong patient survival. Therefore, aiming at early breast cancer and lymph node metastasis, the development of an accurate imaging method and timely and effective treatment have very important significance for prolonging the life cycle of a patient and improving the life quality of the patient.
Disclosure of Invention
The object of the present invention is to provide188The Re-labeled degradable nano probe for breast cancer diagnosis and treatment and the preparation method thereof are used for solving the problems in the background technology.
To achieve the above object, the present inventionThe technical scheme is as follows:188the Re-labeled degradable nano probe for breast cancer diagnosis and treatment comprises a nano probe, wherein the nano probe is composed of PLGA nano particles coated with an IDO inhibitor, and the nano probe comprises the following components in molar mass: 4-6mol of lactide, 1-2mol of glycolide, an initiator, a surfactant, an IDO inhibitor and a dispersant, wherein the nanoprobe is connected with folic acid for targeting 4T1 breast cancer and connected with folic acid188Re is used for target tracking of breast cancer and lymph node metastasis, SPECT imaging and internal irradiation sensitization treatment.
As a further optimization, the initiator is stannous octoate.
As a further optimization, the dispersing agent is PEG.
As a further optimization, the surfactant is PIC-PEO.
The invention also provides188The preparation method of the Re-marked degradable nano probe for breast cancer diagnosis and treatment comprises the following steps,
s1) mixing lactide and glycolide, adding an initiator, and carrying out ring-opening polymerization in a melting way under a vacuum condition to obtain PLGA;
s2) dissolving PLGA and a surfactant in an IDO inhibitor, adding a dispersing agent, and preparing a nano probe by controlling the microfluidic extrusion speed;
s3) connecting folic acid on the nanoprobe;
s4) attachment to the nanoprobe188Re。
As a further optimization, the initiator is stannous octoate; the dispersing agent is PEG; the surfactant is PIC-PEO.
As a further optimization, the ligation on the nanoprobes in S4188The method of Re comprises the steps of,
s41) DOTA-188Re is mixed with the nano probe which is prepared by S3 and is connected with folic acid, the pH value and the temperature are adjusted, and the nano probe is replaced to obtain the nano probe connected with folic acid188A nanoprobe of Re;
s42) by centrifugation or filtration, the unlabeled188And Re is removed.
As a further optimization, the pH in S41 was 4.6 and the temperature was 70 ℃.
The multifunctional nanoprobe has good accurate diagnosis potential for early breast cancer and lymph node metastasis, and is considered as an excellent carrier of internal irradiation radionuclide due to the good tumor passive targeting effect (EPR effect) and easy preparation and modification (convenient connection with tumor targeting molecules). The combination of immunotherapy and radiotherapy has potential application value and very important research significance. The activation state and functional characteristics of T cells in the tumor microenvironment often determine the outcome of the body's anti-tumor immune response, and thus, the activation of T lymphocytes is a key issue in tumor immunotherapy. Indoleamine 2, 3-dioxygenase (IDO) is used as a rate-limiting enzyme of tryptophan metabolism, can promote the tryptophan concentration required by the proliferation of T lymphocytes in tumor parts to be reduced sharply, and forms kynurenine which can activate regulatory T lymphocytes (Tregs), thereby inhibiting the proliferation and activity of the T lymphocytes. Therefore, the tumor immunotherapy taking IDO as a target has great application prospect.
The invention takes PLGA nano-particles coated with IDO inhibitor as a carrier, Folic Acid (FA) molecules capable of targeting 4T1 breast cancer are connected on the material to obtain PLGA-IDO degradable nano-probe capable of targeting breast cancer, and the degradable nano-probe is connected with the PLGA-IDO degradable nano-probe188Re (rhenium, a radionuclide element),188re can emit beta rays of 2.12MeV and gamma rays of 155KeV, and the material can be used for targeting breast cancer and lymph node metastasis to carry out in-vivo irradiation sensitization treatment (beta rays) on a focus and simultaneously can carry out SPECT imaging (gamma rays) on the breast cancer and the lymph node metastasis. Based on this, this multifunctional probe can realize to target tracking, SPECT formation of image and the interior irradiation of mammary cancer and lymph node metastasis increase quick accurate treatment, realizes the integration of diagnosing of mammary cancer.
Drawings
FIG. 1 is a scanning electron microscope image of the nanoprobe of the present invention.
FIG. 2 is a PET-CT showing the enrichment of nanoprobes in breast cancer regions.
Detailed Description
The following are specific embodiments of the present invention, and the technical solutions of the present invention will be further described with reference to the drawings, but the present invention is not limited to these embodiments.
Example 1
188The Re-labeled degradable nano probe for breast cancer diagnosis and treatment consists of PLGA nano particles encapsulating IDO inhibitor, and the nano probe comprises the following components in molar mass: lactide 4mol, glycolide 1mol, stannous octoate, surfactant PIC-PEO, IDO inhibitor and dispersant PEG, wherein the nanoprobe is connected with folic acid for targeting 4T1 breast cancer and connected with folic acid188Re is used for target tracking of breast cancer and lymph node metastasis, SPECT imaging and internal irradiation sensitization treatment.
The preparation method comprises the following steps: s1) mixing lactide and glycolide, adding an initiator, and carrying out ring-opening polymerization in a melting way under a vacuum condition to obtain PLGA; s2) dissolving PLGA and a surfactant in an IDO inhibitor, adding a dispersing agent, and preparing a nano probe by controlling the microfluidic extrusion speed; s3) connecting folic acid on the nanoprobe;
s4) attachment to the nanoprobe188Re：
S41) DOTA-188Re is mixed with the nano probe which is prepared by S3 and is connected with folic acid, the pH value is adjusted to 4.6, the temperature is adjusted to 70 ℃, and the nano probe is replaced to obtain the nano probe connected with folic acid188A nanoprobe of Re; s42) by centrifugation or filtration, the unlabeled188And Re is removed.
The specific embodiments described herein are merely illustrative of the spirit of the invention. Various modifications or additions may be made to the described embodiments or alternatives may be employed by those skilled in the art without departing from the spirit or ambit of the invention as defined in the appended claims.
Claims (8)
1.188The Re-labeled degradable nano probe for breast cancer diagnosis and treatment is characterized by comprising a nano probe, wherein the nano probe is composed of PLGA nano particles coated with an IDO inhibitor, and the nano probe comprises the following components in molar mass: 4-6mol of lactide, 1-2mol of glycolide and an initiatorA surfactant, an IDO inhibitor and a dispersant, wherein the nanoprobe is connected with folic acid for targeting 4T1 breast cancer and is connected with folic acid188Re is used for target tracking of breast cancer and lymph node metastasis, SPECT imaging and internal irradiation sensitization treatment.
2. The method of claim 1188The Re-labeled degradable nano probe for breast cancer diagnosis and treatment is characterized in that the initiator is stannous octoate.
3. The method of claim 1188The Re-labeled degradable nano probe for breast cancer diagnosis and treatment is characterized in that the dispersant is PEG.
4. The method of claim 1188The Re-labeled degradable nano probe for breast cancer diagnosis and treatment is characterized in that the surfactant is PIC-PEO.
5. A method according to any one of claims 1 to 4188The preparation method of the Re-marked degradable nano probe for breast cancer diagnosis and treatment is characterized by comprising the following steps,
s1) mixing lactide and glycolide, adding an initiator, and carrying out ring-opening polymerization in a melting way under a vacuum condition to obtain PLGA;
s2) dissolving PLGA and a surfactant in an IDO inhibitor, adding a dispersing agent, and preparing a nano probe by controlling the microfluidic extrusion speed;
s3) connecting folic acid on the nanoprobe;
s4) attachment to the nanoprobe188Re。
6. The method of claim 5188The preparation method of the Re-labeled degradable nano probe for breast cancer diagnosis and treatment is characterized in that the initiator is stannous octoate; the dispersing agent is PEG; the surfactant is PIC-PEO.
7. The method of claim 5188The preparation method of the Re-labeled degradable nanoprobe for breast cancer diagnosis and treatment is characterized in that the nanoprobe is connected in S4188The method of Re comprises the steps of,
s41) DOTA-188Re is mixed with the nano probe which is prepared by S3 and is connected with folic acid, the pH value and the temperature are adjusted, and the nano probe is replaced to obtain the nano probe connected with folic acid188A nanoprobe of Re;
s42) by centrifugation or filtration, the unlabeled188And Re is removed.
8. The method of claim 7188The preparation method of the Re-labeled degradable nanoprobe for breast cancer diagnosis and treatment is characterized in that the pH value in S41 is 4.6, and the temperature is 70 ℃.
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2021
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Patent Citations (4)
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| US20180126002A1 (en) * | 2015-04-28 | 2018-05-10 | University Of Central Florida Research Foundation, Inc. | Methods and compositions for theranostic nanoparticles |
| CN109069666A (en) * | 2016-04-29 | 2018-12-21 | 纪念斯隆凯特琳癌症中心 | Make to target particle penetration, distribution and in response to the composition and method in malignant brain tumor |
| CN107007835A (en) * | 2017-05-31 | 2017-08-04 | 重庆医科大学 | Carry Prussian blue targeted nano compound and preparation method thereof |
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