Construction Of Targeting Nanoplatform Of Drug Delivery System For Cancer Therapy Research

With the rapid development of nanotechnology,it is anticipated that nanoparticle-based drug delivery systems are able to increase the tumor-targeting aggregation of the phototherapeutic agents to augment the tumor treatment performance.Focused on the treatment strategies of tumor with efficient and low side effects in this thesis.The novel nanocarriers with excellent mitochondria targeting were designed and prepared firstly.Based on the nature of mitochondria:highly hydrophobicity and negative charged membrane,we proposed that the multifunctional nanocarriers were composed of polycations and carbon nanotubes.Subsequently,we designed and prepared a nanocarrier with excellent nuclear targeting also by TAT with the high nuclear targeting performanc.In the second chapter,a series of reductive degradable polyethylene glycol-polyamidoamine amphiphilic cationic hyperbranched copolymers(rPAAs)were prepared by Michael addition with polyethylene glycol diacrylate,N,N'-bis(acryloyl)cystamine(CBA)and triamine,then dodecylamine as the end groups.FT-IR,1H NMR,GPC were used to characterize the structure of the obtained polymers.Then the self-assembly profiles of the polymers and size,zeta potential,cytotoxicity,buffer capacity and intracellular RNA delivery of the nanocarriers were investigated.In the third chapter,one typical copolymer was selected to bind single-walled carbon nanotubes(SWCNTs),which formed rPAA@SWCNTs.Then,load the phototherapeutic agent,indocyanine green reagent(ICG)was immobilized in the nanocarriers by electrostatic interaction to form a mitochondrial targeting nanoplatform(ICG/rPAA@SWCNTs).The high buffer capacity of the polycations facilitated the endosomal escape of nanoparticles via a proton-sponge effect,which was determined by confocal laser scanning microscopy(CLSM).Upon near infrared(808 nm)irradiation,ICG/rPAA@SWCNTs could exert photothennal and photodynamic effect concurrently,which caused irreversible damage of mitochondria.Therefore,mitochondria were activated to overproduce ROS and accumulation in mitochondria,resulting in mitochondrial collapse and irreversible cell apoptosis.Subsequently,the MTT assay,CLSM,FACS were used to evaluate the amplified treatment effect of phototherapy.In the fourth chapter,the amphiphilic polyamine-amines block copolymers PEI-PAA-PEI and PEG-PAA-PEG were prepared firstly by modification polyamine-amines with polyethyleneimine and polyethylene glycol and be uniform dispersed in aqueous solution to prepare the mixed nano-micelles(MNPs).Subsequently the MNPs were was surface modification with TAT as a nuclear targeting group form a nuclear targeting nano-drug delivery system(TAT-MNPs).Then characterized by FT-IR,1H NMR and DLS,and the nuclear targeting properties were studied by confocal fluorescence imaging.It was found that the number of TAT that modified on the surface of MNPs was a key factor affecting its nuclear targeting properties.