| Cancer is one of the threats to human health.The early diagnosis and treatment of cancer is the most effective way to improve the clinical outcomes,and finally decrease the mortality of cancer patients.The development of precision medicine is to diagnose early and refine the individualized treatment in the near future,which is to provide the correct treatment to patients at the right time.Personalized medicine is becoming a hot topic in the field of biomedical research,and also may become a new model of clinical practice.How to design and prepare technologies that integrating of diagnostic and therapeutic function targeted tumor in one system is the key to realize the personalized medicine.Molecular imaging technology which integrates traditional medical imaging technology and molecular biology,makes the biological molecules and basic cellular processes to realize visualization,so as to realize the observation of the occurrence and development and metastasis of cancer cells at the cellular and molecular level,offering an improvement in the early cancer detection,accurate cancer staging and prognosis of cancer for better clinical treatment.In addition,the development of nanotechnology provides an important basis for the effective diagnosis and treatment of a variety of diseases.Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in the world.Its morbidity and mortality are increasing year by year.Most of liver cancer is resistant to chemotherapeutic drugs,and one of the most basic features of HCC is easy to metastasis and recurrent after treatment.Therefore,it is very urgent to develop an effective and reliable tumor biomarker to predict the metastasis and prognosis of HCC.Glyphican-3(phosphatidylinositol-3)is one of the members in heparan sulfate glycoprotein families(heroransulfateproteoglycan,HSPG).The earlier study demonstrated that the mRNA and protein levels of GPC3 protein was high expression in primary hepatocellular carcinoma,but was low or no expression in other tumor and benign liver disease.GPC3 protein could be used as a specific tumor biomarker in HCC because of the high sensitivity and specificity in the diagnosis of primary hepatocellular carcinoma.We reasoned that a novel peptide that specifically recognizes GPC3 would facilitate early detection of HCC and guide the cancer treatment strategy.In this study,phage display screening technology was utilized to obtain GPC3 binding peptides using HCC cells(HepG2;GPC3 positive)and a peptide(named as GBP)with 735.2 ± 53.6 × 10-9 m affinity to GPC3 was successfully identified.The ability to target GPC3 in vivo was investigated by intravenous injection of GBP labeled with Cy5.5,into a HCC tumor-bearing mouse model.It was found that significant high tumor accumulation(tumor/muscle ratio:6.49 ± 0.55)of Cy5.5-GBP in HepG2 tumors was observed compared with that of the low GPC3 expressing control cancer cell line(PC3)(tumor/muscle ratio:1.15 ± 0.32).Similarly,GBP showed great potential for HCC detection via fluorescent imaging and histological staining.Finally,we engineerd the peptide onto the surface of Fe3O4 nanoparticles and demonstrated the functional nanoparticles as theranostics for the photothermal treatment of tumor under the guidance of the targeted imaging. |
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