Effects On Stem Cell And Targeted Breast Cancer Therapy By Phage-Based Nanoparticles

The number of the patients with neurodegenerative diseases?e.g.,Parkinson,alzheimer disease,epilepsy,huntington disease,stroke?is rapidly increasing with the aging of Chinese population.The neurodegenerative diseases are hard to treat as the traditional medicine could not pass the blood-brain barrier.The neural cells do not proliferate as they are highly differentiated.Hence,the nerve injury has to be repaired by neural cells differentiated from the stem cells.But there is a potential biosafety issue of the traditional stem cell transplantation therapy because of the formation of teratoma from undifferentiated stem cells and the use of the transgenic vectors derived from virus for differentiating stem cells.So another method of inducing stem cell neutral differentiation is needed.BaTiO₃ is a piezoelectric material with the capability of controlling electrical signals.It has the potential to induce stem cells to differentiate into neural cells.In the first project,I finished the first part of the work for inducing the neural stem cell differentiation.Firstly,a BaTiO₃ nanoparticle binding peptide was identified from a phage-displayed random peptide library by bio-panning.Then the peptide was displayed on the major coat proteins?pVIII?to form the engineered phage.The engineered phage was used to induce the nucleation of BaTiO₃ to form the BaTiO₃ nanowires with a high dielectric constant.This study developed a new strategy to synthesize the uniform tetragonal BaTiO₃ nanoparticles with high purity by using the engineered phage under neutral pH at room temperature.This method could be used in the synthesis of other materials.In the meantime,with the development of the urbanization,non-infectious diseases?e.g.,cancer,cardiovascular disease?have occurred more frequently than the infectious diseases.Cancer has become the most important public health problem due to its high mortality and increasing incidence.About 12,000 of new incidences occur on average in one day.Breast cancer is the most common cancer in women worldwide.It is the second most common cancer type in women in China.According to the statistics of World Health Organization,about 15%of breast cancer patients are in China.The mortality of breast cancer ranks the sixth among all the cancer types in women in China.The age of women getting breast cancer,mostly 35-40 years old,is younger in China than that in the rest of the world.On the other hand,as the current breast cancer therapies in China are mammectomy and chemotherapy in stead of the breast conservative operation,the breast cancer is more harmful and dangerous to Chinese women.Hence,the development of personalized targeted treatments is very important and urgent in order to eradicate breast cancer.The current personalized breast cancer treatments are based on targeting tumor cells,the tumor micro-environment or immune escape.In 1971,Dr.Folkman at Harvard University proposed an angiogenesis hypothesis that the tumor growth relies on the genetation of new vessels that can provide the nutrition to tumors and remove metabolites.The hypothesis has turned out to be correct.The tumor cells always secret the angiogenc factors to stimulate the pathological angiogenesis.If the angiogenic factors are blocked,the tumor will“starve”due to the absence of enough new vessels.I carried out the second study,developing a new angiogenesis targeting nano-drug,to achieve the personalized treatment of breast cancer.The peptide which could bind to Angiogenin,an important angiogenic factor,was identified firstly from a phage-displayed random peptide library by bio-panning.Then the angiogenin-binding peptide and the human breast cancer homing peptide were displayed on the major coat?pVIII?and at the tip?pIII?of the fd phage,respectively,using an fd388 double-display vector,resulting in the formation of double-displayed phages.At last,the double-displayed phage particles were found to target tumor and inhibit tumor angiogenesis for targeted breast cancer therapy.The significance of the second study includes:The peptide drug could keep its original space structure and biological function after displayed on the phage coating proteins.the strategy developed in this study could be extended to other studies of inhibiting the cytokines and biomacromolecules.The results demonstrate that the double-displayed phage could selectively inhibit the growth of human breast tumor by inhibiting tumor angiogenesis.Such targeted anti-angiogenesis method could also be applied to the treatment of other cancer types.