Construction Of Gene Vetors Based On Supramolecular Host-Guest Assembly Of Cyclodextrin

The target of gene therapy is the insert of functional genes in particular cells to treat disease resulting from genetic defect. One of the most important problems of gene therapy is to build up gene vectors with high-transfection and low-toxicity. Compared with viral vectors, nonviral vectors have received significant attention because of low toxic ity, relatively low production cost, and stability. Supramolecular host-guest assembly based on cyclotron demonstrates intense applications in gene theratpy. Bioreducible gene carriers can reduce the toxicity and improve the transfection efficiency. Special morphology such as rodlike nanoparticles displayed higher cell internalization rates. Gold nanorods possess the functions of photoacoustic imaging and photothermal therapy due to the absorption wavelength in infrared region. Based on the background mentioned above, the research projects were shown as follows:1. The reducible polyrotaxane (PR)-based cationic block copolymer (SS-PR) was prepared via ATRP of DMAEMA based on the self-assembled pseudo-PR. A series of pseudo-comb polycations (SS-PR-pDM) with different molecular weights were subsequently produced via two-step ATRP of DMAEMA by using bromoisobutylryl-functionalized SS-PR as the macroinitiator. SS-PR-pDM exhibited the enhanced pDNA-condensing ability and similarly low toxicity compared with SS-PR. Meanwhile, SS-PR-pDM displayed higher cell internalization rates and luciferase gene transfection efficiency. Furthermore, the favorable property of the pseudo-comb SS-PR-pDM benefited pDNA entering the nucleus. The present work demonstrates that properly grafting cationic side chains from reducible PR backbones via consecutive ATRP processes was one effective means to produce new PR-based supramolecular polycations.2. In order to prepare vectors with the functions of photoacoustic imaging and photothermal therapy, acicular cellulose nanocrystals (CNC)-gold nanoparticles (spherical particles or nanorods) was prepared as substrate (CNC-NR or CNC-NP). First, cationic polymer (CD-PGEA) was first prepared through ATRP of glycidyl methacrylate (GMA) and the subsequent EA functionalization using the ?-cyclodextrin (?-CD) functionalized by BIBB as the initiator. Polyethylene glycol (PEG) with one side functionalized by adamantine, and the other side by lipoic acid (LA) was then prepared as intermediate (Ad-PEG-LA). Acicular fiber-gold nanoparticles were assembled with cationic polymer by Au-S bond and host-guest interaction of CD and Ad (CNC-NR-PGEA or CNC-NP-PGEA). Compared with CD-PGEA, cellular uptake and transfection efficiency were improved. The transfection efficiencies of CNC-NR-PGEA and CNC-NP-PGEA are similar. In addition to the capability of photoacoustic imaging, CNC-NR-PGEA could realize combined photothermy and gene therapy to inhibit the growth of cancer cells.