Study On Construction Of Protein-Based Functional Nano-Biomaterials And Efficient Tumor Treatment

With the proposal and in-depth research of nanomedicine,nanotechnology has opened a new avenue for the early diagnosis and precise treatment of cancer.As a natural biomacromolecule,protein has good biocompatibility,unique three dimentional conformation and inherent functionalities,displaying considerable potentials for pratical applications in bio-medicine.Herein,focus on the innovative synthesis of self-assembly systems of different protein components,we have systematically carried out the synthesis of protein-based nano-biomaterials and the researches on effective treatments of tumors,which will be of great guidance for the construction of clinically applicable nano-biomaterials.The research includes the following contents:?1?A bioenvironment-responsive versatile nanoplatform enabling rapid clearance and effective tumor homing for oxygen-enhanced radiotherapy?RT?:Bismuth sulfide-albumin composite nanospheres followed by catalase conjugation?denoted as BSNSs-CAT?has been well constructed as a bioenvironment-responsive nanoplatform.The BSNSs-CAT phagocytosed by normal cells demonstrate architecture disintegration into small one in response to physiological pH,achieving small size-favored rapid clearance,which largely mitigates the concern of long-term toxicity of BSNSs-CAT in normal tissues.While BSNSs-CAT remain architecturally stable in mild acidic tumor microenvironment?TME?,which strongly favors to response with H₂O₂ overproduced TME.As a result,the produced intratumor oxygen could overcome tumor hypoxia-associated RT resistance,together with the radiosensitization effect of bismuth,collectively enhancing RT efficacy.Therefore,the constructed BSNSs-CAT can effectively overcome the RT resistance of hypoxic tumor cells,improving the enhancement effect of radiosensitizer,and simultaneously reduce its long-term retention in normal tissues,ensuring the high safety of the treatment.?2?Inlaying radiosensitizer onto the polypeptide shell of drug-loaded ferritin for imaging and combinational chemo-radiotherapy:To avoid the side effects of free anticancer-drugs on normal tissues and improve the efficacy of such a monotherapy modality,herein a novel ferritin nanotheranostic was synthesized.The Dox molecules encapsulated in the interior of ferritin can selectively release in the mildly acidic lysosome compartment and induce cancer cells death consequently.While the bismuth sulfide nanocrystals onto the polypeptide shell can strengthen the architectural stability of ferritin to prevent drug burst leakage,act as excellent computed tomography contrast agents for in vivo imaging-guided cancer treatment,and simultaneously enhance RT efficacy based on the radio-sensitization effect,which cooperates with the doxorubicin benefited chemotherapy,significantly inhibit the tumor growth and improve the survival rate of tumor-bearing mice.?3?Transferrin receptor-mediated sequential intercellular nanoparticles relay for tumor deep penetration and sonodynamic therapy:The novel reactive oxygen species?ROS?-mediated cancer sonodynamic therapy displays unique advantages of high selectivity,non-radiation,non-invasiveness and deep tissue penetrability,whereas the poor tumor penetration of sonosensitizers largely lowers the therapeutic effectiveness.Here,a new type of nanosonosensitizer self-assembled from transferrin and organic sonosensitizer protoporphyrin IX has been firstly designed.The nanosonosensitizers inherit the unique transferrin receptor?TfR?-mediated endocytosis and exocytosis behaviors of transferrin,enabling specifically binding to TfR-overexpressed tumor cells and thereafter TfR-mediated sequential intercellular delivery of nanosonosensitizers.Consequently,tumor deep delivery of sonosensitizers is achieved in TfR-overexpressed HeLa tumor,which is considerably beneficial for the inhibition of tumor growth with aboundant ROS generation upon the activation of external ultrasound.