LYP-1 targeted composite nano-material for diagnosis and treatment of pancreatic cancer lymphatic metastasis and application of LYP-1 targeted composite nano-material

Abstract

The invention belongs to the technical field of clinical diagnosis and treatment, and provides an LYP-1 targeted composite nano-material for diagnosis and treatment of pancreatic cancer lymphatic metastasis and application of the LYP-1 targeted composite nano-material for diagnosis and treatment of pancreatic cancer lymphatic metastasis, the LYP-1 targeted composite nano-material for diagnosis and treatment of pancreatic cancer lymphatic metastasis comprises a LyP-1 polypeptide modified nano-carrier and a loaded diagnosis and treatment agent, the diagnosis and treatment agent is a treatment drug or a diagnosis marker aiming at pancreatic cancer lymphatic metastasis; through the LyP-1 polypeptide modified nano-carrier, efficient targeting of the pancreatic cancer lymphatic metastasis part is realized; as a targeting molecule, the LyP-1 polypeptide can specifically recognize and bind to pancreatic cancer lymphatic metastatic cells, so that the aggregation concentration of the nano material at a focus part is improved, the treatment effect is enhanced, and the damage to normal tissues is reduced.

Description

Technical Field

[0001] The present invention belongs to the technical field of clinical diagnosis and treatment, and specifically relates to a LYP-1 targeted composite nanomaterial for diagnosis and treatment of pancreatic cancer lymph node metastasis and application thereof. Background Art

[0002] Pancreatic cancer is a highly malignant tumor with high morbidity and mortality rates worldwide. Lymphatic metastasis, as an important metastatic pathway of pancreatic cancer, not only accelerates the deterioration of the disease, but also greatly affects the patient's prognosis and quality of life.

[0003] At present, the clinical treatments for pancreatic cancer lymph node metastasis mainly include surgical resection, chemotherapy, radiotherapy, etc. However, most of the above-mentioned diagnosis and treatment methods lack the specific targeting ability for pancreatic cancer lymph node metastasis, resulting in poor treatment effects and obvious side effects.

[0004] To this end, those skilled in the art have proposed LYP-1 targeted composite nanomaterials for diagnosis and treatment of pancreatic cancer lymph node metastasis and their applications to solve the problems raised by the background technology. Summary of the invention

[0005] In order to solve the above technical problems, the present invention provides LYP-1 targeted composite nanomaterials and applications thereof for diagnosis and treatment of pancreatic cancer lymph node metastasis, so as to solve the problems of poor targeting and large side effects in the prior art methods for treating pancreatic cancer lymph node metastasis.

[0006] The invention discloses a LYP-1 targeted composite nanomaterial for the diagnosis and treatment of pancreatic cancer lymph node metastasis, comprising: a LyP-1 polypeptide-modified nanocarrier and a loaded diagnostic agent, wherein the diagnostic agent is a therapeutic drug or a diagnostic marker for pancreatic cancer lymph node metastasis.

[0007] Preferably, the nanocarrier is at least one of a metal organic framework, a biodegradable polymer, a carbon nanotube, a magnetic nanoparticle and a smart responsive polymer. The smart responsive polymer can release drugs according to changes in the microenvironment (including pH value, temperature or enzyme activity) of the pancreatic cancer lymphatic metastasis site, and can more accurately control the release of diagnostic and therapeutic agents, thereby improving the bioavailability and targeting efficiency of the drug.

[0008] Preferably, the diagnostic and therapeutic agent is one or more of a chemotherapeutic drug, a gene therapy drug, a radioisotope label, a fluorescent label, a gene therapy drug, a photosensitizer and an immunomodulator.

[0009] Preferably, the surface of the nanocarrier is linked to the LyP-1 polypeptide via a covalent bond or a non-covalent bond to achieve targeting.

[0010] Preferably, the nanocarrier has good biocompatibility and stability, and can effectively inhibit pancreatic cancer lymph node metastasis in vivo and in vitro.

[0011] The method for preparing the LYP-1 targeted composite nanomaterial for the diagnosis and treatment of pancreatic cancer lymph node metastasis comprises the following steps: preparing a nanocarrier, modifying the LyP-1 polypeptide onto the surface of the nanocarrier, and loading a diagnostic and therapeutic agent.

[0012] Preferably, the nanocarrier is prepared by chemical synthesis or physical methods, and the LyP-1 polypeptide is connected to the surface of the nanocarrier by a coupling reaction. The steps of preparing the nanocarrier by chemical synthesis method include selecting appropriate chemical raw materials, performing chemical reactions under specific reaction conditions, such as solution reaction, vapor deposition or sol-gel method, etc., to form the desired nanostructure, and then undergoing subsequent purification and surface modification to obtain a stable and functionalized nanocarrier.

[0013] The physical method for preparing nanocarriers comprises the following steps: utilizing physical principles and techniques, such as mechanical ball milling, laser evaporation, physical vapor deposition or sputtering coating, to directly convert bulk materials into nanoscale particles or films, and controlling the morphology, size and performance of the nanocarriers by adjusting parameters in the preparation process, and finally obtaining nanocarrier materials that meet the requirements.

[0014] According to the above-mentioned LyP-1 targeted composite nanomaterial for diagnosis and treatment of pancreatic cancer lymph node metastasis, it is used in the preparation of drugs for treating or diagnosing pancreatic cancer lymph node metastasis.

[0015] Preferably, the method comprises: using bioinformatics technology to perform deep sequencing and analysis on pancreatic cancer lymph node metastasis tissues, screening out biomarkers closely related to pancreatic cancer lymph node metastasis, and then using these biomarkers to design a more accurate LyP-1 polypeptide modification strategy to improve the targeting ability of nanomaterials to pancreatic cancer lymph node metastasis sites; the bioinformatics technology uses a support vector machine (SVM) to train and predict biomarker data to screen out the most important biomarkers;

[0016] Subsequently, diagnostic markers (including fluorescent markers, radioisotope markers) and therapeutic drugs (including chemotherapy drugs, gene therapy drugs) are simultaneously loaded into the nanocarrier, and the nanomaterials are delivered to the site of pancreatic cancer lymph node metastasis through a precise targeting mechanism, thus achieving the dual functions of simultaneous diagnosis and treatment.

[0017] Preferably, by collecting the patient's clinical data, genomic information, and imaging data of pancreatic cancer lymph node metastasis sites, an artificial intelligence algorithm is used to personalize the treatment plan, and the loading amount, release rate, and treatment strategy of the nanomaterial are adjusted according to the patient's specific situation to improve the treatment effect and reduce side effects.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] 1. The present invention achieves efficient targeting of pancreatic cancer lymph node metastasis sites through LyP-1 polypeptide-modified nanocarriers; LyP-1 polypeptide, as a targeting molecule, can specifically recognize and bind to pancreatic cancer lymph node metastasis cells, thereby increasing the aggregation concentration of nanomaterials at the lesion site, enhancing the therapeutic effect and reducing damage to normal tissues.

[0020] 2. The nanocarriers used in the present invention have a variety of options, including metal organic frameworks, biodegradable polymers, carbon nanotubes, magnetic nanoparticles and smart responsive polymers. These carriers not only have good biocompatibility and stability, but can also accurately control the release of diagnostic and therapeutic agents according to the microenvironment changes in the pancreatic cancer lymph node metastasis site, thereby improving the bioavailability and targeting efficiency of the drugs.

[0021] 3. The present invention combines bioinformatics technology and artificial intelligence algorithms, and screens out biomarkers closely related to pancreatic cancer lymph node metastasis through deep sequencing and analysis of pancreatic cancer lymph node metastasis tissue, and uses these biomarkers to design a more accurate LyP-1 polypeptide modification strategy; at the same time, according to the patient's clinical data, genomic information and imaging data, the treatment plan is personalized and the loading amount, release rate and treatment strategy of the nanomaterial are adjusted, which further improves the treatment effect and reduces side effects; this personalized precision medicine model provides new ideas and directions for the treatment of pancreatic cancer lymph node metastasis. DETAILED DESCRIPTION

[0022] The following examples are used to illustrate the present invention, but they are not intended to limit the scope of the present invention.

[0023] Embodiment: The present invention provides a LYP-1 targeted composite nanomaterial for diagnosis and treatment of pancreatic cancer lymph node metastasis, comprising: a LyP-1 polypeptide-modified nanocarrier and a loaded diagnostic and therapeutic agent, wherein the diagnostic and therapeutic agent is a therapeutic drug or a diagnostic marker for pancreatic cancer lymph node metastasis;

[0024] The nanocarrier is at least one of a metal organic framework, a biodegradable polymer, a carbon nanotube, a magnetic nanoparticle, and an intelligent responsive polymer. The intelligent responsive polymer can release the drug according to the changes in the microenvironment (including pH value, temperature or enzyme activity) of the pancreatic cancer lymph node metastasis site, and can more accurately control the release of the diagnostic and therapeutic agent, thereby improving the bioavailability and targeting efficiency of the drug.

[0025] The diagnostic and therapeutic agent is one or more of a chemotherapeutic drug, a gene therapy drug, a radioisotope marker, a fluorescent marker, a gene therapy drug, a photosensitizer, and an immunomodulator;

[0026] The surface of the nanocarrier is connected to LyP-1 polypeptide via covalent bonds or non-covalent bonds to achieve targeting;

[0027] The nanocarrier has good biocompatibility and stability, and can effectively inhibit pancreatic cancer lymph node metastasis in vivo and in vitro.

[0028] From the above, it can be seen that the LYP-1 targeted composite nanomaterial used for the diagnosis and treatment of pancreatic cancer lymph node metastasis achieves efficient and precise treatment of pancreatic cancer lymph node metastasis sites by adopting various types of nanocarriers to load diagnostic and therapeutic agents and combining targeted modification of LyP-1 polypeptides. At the same time, the intelligent responsive polymer can accurately control drug release according to changes in the lesion microenvironment, thereby improving the bioavailability and targeting efficiency of the drug. The nanocarrier has good biocompatibility and stability, effectively inhibiting pancreatic cancer lymph node metastasis, significantly improving the treatment effect and reducing side effects.

[0029] According to the above-mentioned method for preparing LYP-1 targeted composite nanomaterials for the diagnosis and treatment of pancreatic cancer lymph node metastasis, the method includes the following steps: preparing a nanocarrier, modifying the LyP-1 polypeptide to the surface of the nanocarrier, and loading the diagnostic and therapeutic agent; the nanocarrier is prepared by chemical synthesis or physical methods, and the LyP-1 polypeptide is connected to the surface of the nanocarrier by a coupling reaction.

[0030] According to the above-mentioned LyP-1 targeted composite nanomaterial for diagnosis and treatment of pancreatic cancer lymph node metastasis, it is used in the preparation of drugs for treating or diagnosing pancreatic cancer lymph node metastasis.

[0031] Further, the method includes: using bioinformatics technology to perform deep sequencing and analysis on pancreatic cancer lymph node metastasis tissues to screen out biomarkers closely related to pancreatic cancer lymph node metastasis, and then using these biomarkers to design a more accurate LyP-1 polypeptide modification strategy to improve the targeting ability of nanomaterials to pancreatic cancer lymph node metastasis sites; the bioinformatics technology uses a support vector machine (SVM) to train and predict biomarker data to screen out the most important biomarkers, and the algorithm formula of the support vector machine is as follows:

[0032]

[0033] Among them, w is the weight vector, b is the bias term, and X i is the input vector (including biomarker expression levels, patient clinical data, etc.), y i is the target variable (including pancreatic cancer lymph node metastasis status), n is the number of samples;

[0034] Subsequently, diagnostic markers (including fluorescent markers, radioisotope markers) and therapeutic drugs (including chemotherapy drugs, gene therapy drugs) are simultaneously loaded into the nanocarrier, and the nanomaterials are delivered to the site of pancreatic cancer lymph node metastasis through a precise targeting mechanism, thus achieving the dual functions of simultaneous diagnosis and treatment.

[0035] From the above, we can see that by using bioinformatics technology to perform deep sequencing and analysis of pancreatic cancer lymph node metastasis tissues and using support vector machines to screen key biomarkers, we can accurately design LyP-1 peptide modification strategies, significantly improve the targeting ability of nanomaterials to pancreatic cancer lymph node metastasis sites, and achieve precise delivery of diagnostic and therapeutic agents. At the same time, loading diagnostic markers and therapeutic drugs in nanocarriers can not only achieve early and accurate diagnosis of the disease, but also carry out targeted treatment in a timely manner, effectively improving the treatment efficiency and success rate of pancreatic cancer lymph node metastasis, and bringing patients a better treatment experience and prognosis.

[0036] Furthermore, by collecting the patient's clinical data, genomic information and imaging data of pancreatic cancer lymph node metastasis, the artificial intelligence algorithm is used to personalize the treatment plan, and the loading amount, release rate and treatment strategy of the nanomaterial are adjusted according to the patient's specific situation to improve the treatment effect and reduce side effects. The formula of the artificial intelligence algorithm is as follows:

[0037] θ t+1 =θ t -η·▽ θ L(θ t );

[0038] Where θ represents the model parameters (including the loading amount and release rate of nanomaterials), η is the learning rate, L(θ) is the loss function (indicating the difference between the treatment plan and the desired target), ▽ θ L(θ t ) is the gradient of the loss function with respect to the model parameters.

[0039] From the above, we can see that by collecting multi-dimensional data of patients and using artificial intelligence algorithms to design personalized treatment plans, the loading amount, release rate and treatment strategy of nanomaterials can be accurately adjusted according to the specific conditions of the patients, thereby maximizing the treatment effect and reducing side effects; this intelligent precision medicine model not only improves the targetedness and effectiveness of treatment, but also provides patients with safer and more reliable treatment options, and is expected to bring revolutionary breakthroughs in the treatment of pancreatic cancer lymph node metastasis.

[0040] The embodiments of the present invention are provided for the purpose of illustration and description. Although the embodiments of the present invention have been shown and described above, it can be understood that the above embodiments are exemplary and cannot be understood as limitations of the present invention. Ordinary technicians in this field can change, modify, replace and modify the above embodiments within the scope of the present invention.

Claims

1. LYP-1 targeted composite nanomaterial for diagnosis and treatment of pancreatic cancer lymph node metastasis, characterized in that: include: A LyP-1 polypeptide-modified nanocarrier and a loaded diagnostic and therapeutic agent, wherein the diagnostic and therapeutic agent is a therapeutic drug or a diagnostic marker for pancreatic cancer lymph node metastasis.

2. The LYP-1 targeted composite nanomaterial for diagnosis and treatment of pancreatic cancer lymph node metastasis according to claim 1, characterized in that: The nanocarrier is at least one of a metal organic framework, a biodegradable polymer, a carbon nanotube, a magnetic nanoparticle and an intelligent responsive polymer.

3. The LYP-1 targeted composite nanomaterial for diagnosis and treatment of pancreatic cancer lymph node metastasis according to claim 1, characterized in that: The diagnostic and therapeutic agent is one or more of a chemotherapeutic drug, a gene therapy drug, a radioisotope marker, a fluorescent marker, a gene therapy drug, a photosensitizer and an immunomodulator.

4. The LYP-1 targeted composite nanomaterial for diagnosis and treatment of pancreatic cancer lymph node metastasis according to claim 1, characterized in that: The surface of the nanocarrier is connected to the LyP-1 polypeptide via a covalent bond or a non-covalent bond.

5. The LYP-1 targeted composite nanomaterial for diagnosis and treatment of pancreatic cancer lymph node metastasis according to claim 1, characterized in that: The nanocarrier has good biocompatibility and stability, and can effectively inhibit pancreatic cancer lymph node metastasis in vivo and in vitro.

6. The method for preparing the LYP-1 targeted composite nanomaterial for diagnosis and treatment of pancreatic cancer lymph node metastasis according to any one of claims 1 to 5, characterized in that: The following steps are involved: Nanocarriers are prepared, LyP-1 polypeptides are modified onto the surface of the nanocarriers, and diagnostic and therapeutic agents are loaded.

7. The method for preparing the LYP-1 targeted composite nanomaterial for diagnosis and treatment of pancreatic cancer lymph node metastasis according to claim 6, characterized in that: The nanocarrier is prepared by chemical synthesis or physical method, and the LyP-1 polypeptide is connected to the surface of the nanocarrier by coupling reaction.

8. Use of the LyP-1 targeted composite nanomaterial for diagnosis and treatment of pancreatic cancer lymph node metastasis according to claim 6 in the preparation of a drug for treating or diagnosing pancreatic cancer lymph node metastasis.

9. The use according to claim 8, characterized in that: include: Using bioinformatics technology to perform deep sequencing and analysis on pancreatic cancer lymph node metastasis tissues, screen out biomarkers closely related to pancreatic cancer lymph node metastasis, and then use these biomarkers to design a more accurate LyP-1 polypeptide modification strategy; the bioinformatics technology uses a support vector machine to train and predict biomarker data; Subsequently, diagnostic markers and therapeutic drugs are simultaneously loaded into the nanocarriers, and the nanomaterials are delivered to the pancreatic cancer lymph node metastasis site through a precise targeting mechanism.

10. The use according to claim 8, characterized in that: By collecting patients' clinical data, genomic information, and imaging data of pancreatic cancer lymph node metastasis, we use artificial intelligence algorithms to personalize treatment plans and adjust the nanomaterial loading, release rate, and treatment strategy according to the patient's specific situation.

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