Tumor Analysis And Therapy Research Based On Platinum Clusters

As a malignant disease,tumors are a leading cause of untimely deaths among people.Tumors form due to genetic abnormalities that cause cells to lose control over their proliferation,leading to abnormal growth and proliferation of cells in the affected area.Realizing the diagnosis and treatment of tumors in their early stages is an important measure.Due to their unique physicochemical properties and biological effects,nanoparticles are widely used in the field of biomedical.In recent years,with the advancement of nanoparticle preparation technology and their increasing applications,the medical use of nanoparticles has provided more opportunities for early diagnosis and highly effective treatment of tumors.Among these nanoparticles,noble metal clusters,which typically contain several to hundreds of atoms,have the advantage of precise molecular structure,ease of preparation,good biocompatibility,and unique optical properties and biological effects.Therefore,noble metal clusters have been widely used in the field of biomedical,such as biomolecular detection,cell imaging,and tumor treatment.In this research,we plan to prepare atom precise Pt clusters with functional peptides that target integrin αvβ3.At the same time,we aim to ensure that the prepared Pt clusters have high biosafety,unique physicochemical and biological effects.Given their specific targeting ability and enzyme-like catalytic activity,we anticipate that the prepared Pt clusters can label integrin αvβ3 on the surface of cells with high specificity and enable accurate quantitative analysis.Simultaneously,we expect the prepared Pt clusters to exhibit enhanced antitumor activities due to their unique bioeffect and biosafety properties.The main summary of the research work is as follows:(1)Realizing the Analysis and Detection of Different Integrin αvβ3 in Various Tumor Cells Using Pt Clusters Targeting Integrin αvβ3Integrin αvβ3 is overexpressed in a variety of tumors and plays a crucial role in tumorigenesis,invasion,and metastasis.Therefore,the design of a simple and accurate detection method would be of great significance in achieving precise analysis of integrin αvβ3.The experiment utilized RGD peptides targeting integrin αvβ3 as a template,and optimized experimental conditions such as temperature,p H,and material ratio to synthesize platinum clusters.The morphology and size of the platinum clusters were characterized using highresolution transmission electron microscopy and dynamic light scattering,and the fluorescence properties of the clusters were measured using a fluorescence spectrophotometer.The structure composition of the platinum clusters was determined using MALDI-TOF-MS,and their catalytic properties were studied using a TMB catalysis experiment to assess their peroxidase-like activity.After co-incubation with cells,the expression levels of integrin αvβ3 in different tumor cells were evaluated using fluorescence imaging,inductively coupled plasma mass spectrometry(ICP-MS)quantification,and catalytic color imaging.In addition,cell in situ labeling and quantitative analysis of three cell lines(Si Ha,He La,and 16HBE)with different expression levels of integrin αvβ3 were achieved,and visual differentiation of experimental cell lines with different expression levels of integrin αvβ3 was achieved under an ordinary microscope through labeled catalysis.This study provides important ideas for exploring and developing methods for in situ analysis and detection of single cell level tumor marker proteins.(2)The antitumor activities of targeting Pt clustersPlatinum-based drugs,such as cisplatin,carboplatin,and oxaliplatin,are widely used chemotherapy drugs in cancer treatment.They exhibit excellent cytotoxicity by interacting with DNA and causing DNA damage.However,the lack of selectivity and high systemic toxicity of existing platinum-based drugs severely limit their clinical applications.Therefore,improving the targeting of platinum-based drugs is crucial to enhancing their efficacy and reducing toxicity.Platinum clusters have low systemic toxicity and strong potential for tumor-targeted therapy,and have shown good application prospects in clinical practice.In this project,we designed and synthesized platinum clusters targeting integrin αvβ3,which is overexpressed on the surface of tumor cells.We selected highly malignant triple-negative breast cancer cells(4T1 cells)and studied the anti-tumor therapeutic effects of the platinum clusters in vitro and in vivo.In the in vitro experiments,the CCK-8 cell proliferation assay,flow cytometry apoptosis assay,and reactive oxygen species detection verified the inhibitory effect of the platinum clusters on the growth of 4T1 cells and showed no toxicity to normal tissue cells.In the animal experiments,we established a 4T1 subcutaneous tumor model in mice,and tumor volume,tumor tissue apoptosis staining,and tumor tissue H&E staining indicated that the platinum clusters had good anti-tumor therapeutic effects.H&E staining of organs,blood routine examination,and blood biochemical examination showed that the platinum clusters had good biosafety.This study effectively overcomes the systemic toxicity of platinum-based drugs caused by the lack of targeting,and provides a new approach for the design of platinum-based drugs.