Self-assembly Supramolecular Nanoparticles(SNPs) As Immunotherapy And Small Molecular Anticancer Drug Delivery System For Cancer Therapy

Currently, chemotherapy is indispensable to anticancer. But pharmaceutical drug clinical applications were limited because of poor solubility in aqueous solutions, non-specific distribution throughout the body, toxicity to healthy tissues and cancer cell resistance. With the rapid improvement of self-assembly supramolecular nanoparticles (SNPs) in the modern and pharmacology, SNPs used as the carriers of anticancer drug could improve drug water solubility, increase pharmaceutical bioavailability, control the drug loading and the drug release rate. To overcome the multidrug resistance (MDR), the organic combination of chemotherapy drugs and other methods, such as molecular targeted therapy, immune therapy, gene therapy, etc., in order to produce synergistic effect and obtain the best treatment effect.Firstly, we sysnthesized polycation HPC composed of Hydroxypropyl-cyclodextrin (Hy-CyD) cross-linked by low molecular weight PEI600Da. Then we investigated the effects of cationic polymer PEI-β-hy-CyD (P-HPC) treatment of non-small lung cancer (LLC), by co-delivery the transmembrane staphylococcal enterotoxin A (TSA) gene and gefitinib (GFT). Following evaluated the antitumor activity of y-HPC/Ada-Dox (y-PAD). And we confirmed that y-PAD can delivery siRNA and Dox into the cells.The main content and conclusion of this dissertation are summarized below:In part I, cationic polymer β-HPC and GFT can form nanoparticles (3-HPC/GFT through hydrophobic and hydrophilic relationship, β-HPC/GFT surface has positive charge, so it can interact with TSA plasmid to form P-HPC/GFT/TSA complexes by electrostatic interactions.In vitro study, experimental results show that β-HPC/GFT can deliver GFT and TSA gene into LLC cells. And the TSA plasmid can express TSA protein. More importantly, in vivo study, TSA protein can active of immune function in mice, adjust the CD4/CD8in1.5to2.5within the normal range, raise the TNF alpha and IFN-gamma production. Then collaborative injection of β-HPC/GFT, this method suppresses cancer growth more effectively than delivery of either GFT, TSA or β-HPC/GFT/TSA in LLC cancer therapy.In part II, To synthesize a (2-Hydroxypropyl)-y-cyclodextrin-polyethylenimine/adamantane-conjugated doxorubicin (y-PAD) based supramolecular nanoparticles with host-guest interaction. The1H-NMR, NOESY, UV-Vis, XRD and TGA were used to confirm the structure of vector. MTT assay, cell wound healing assay and H/E staining assay show that show that y-PAD have anti-tumor activity. Cell uptake assay showed that y-PAD can carry drug and siRNA into the same cell.