Construction Of Chitosan Fund Nanorods And Study On Its Nano - Drug Carrier

Gold nanoparticles have been widely used in biological detection, diagnosis and treatment, due to their low toxicity, special optical properties and easy to combine with organic molecules. Especially, gold nanorods (GNRs) were used as drug, gene and vaccine delivery system in biomedicine field because of their unique optical properties.Chitosan had good biocompatibility, which is the only basic polysaccharide in nature. The modified chitosan derivatives can be widely applied as drug and gene nanocarners.In this study, a new hybrid nanomaterials were designed and synthesized based on the conjugates of GNRs and chitosan derivatives with low toxicity and biocompatibility, which are suitable for biomedical fields. Doxorubicin (DOX) was chosen as the model drug and loaded into the nanomaterials which were expected to treat with cancer cells combining photothermo- and chemo- effect. The main contents of this work are as follows:1. The chitosan derivatives (CS-PEG-PEI) with different substitution degrees were synthesized by the modified NHS/EDC method, and characterized by 1H NMR. The self-assembled nanoparticles of CS-PEG-PEI was prepared by probe sonication-dialysis method, and characterized by transmission electron microscope (TEM) and dynamic light scattering (DLS). The results showed that the size of self-assembled nanoparticles was about 200 nm, and the distribution was uniform. The cell viability was detected by CCK-8 assay, which were treated with the nanoparticles of CS-PEG-PEI. And the results shown that the cell viability was over 90%, even at the concentration of the blank nanoparticles 200 ug/mL.2. GNRs were synthesized by seed mediated growth procedure. Two special absorption peaks were observed in UV-vis spectrum of GNRs. The nanocarriers of CS-GNRs were prepared by probe sonication-dialysis method combining the nanoparticles of CS-PEG-PEI with GNRs. Crystal violet (CV) was chosen as model probe, and the obvious Surface-enhanced Raman scattering (SERS) effect of CS-GNRs was shown. The raw GNRs exhibited very high cytotoxicity on cells even at low concentration, and the cell viability of CS-GNRs was obvious improved.3. Doxorubicin (DOX) was chosen as the model drug, and the DOX-CS-GNRs were prepared by probe sonication-dialysis method which uniform size and size distribution. With increasing of the ratio of durg/nanoparticles, the drug loading content of DOX-CS-GNRs increased, but the encapsulation efficiency decreased. The drug release behavior of DOX-CS-GNRs was studied in in vitro. And the results shown that the release behavior was ph-responsive, the drug released more completed in the medium with lower pH value. The release behavior of DOX was NIR-responsive, the drug release increased when the DOX-CS-GNRs were irradiated with a near infrared (NIR) laser. Confocal image analysis obtained that free DOX was mainly distributed in the nucleus, while DOX-CS-GNRs were in the cytoplasm.The results of in vitro cytotoxicity assay shown that the cells inhibition effect of DOX-CS-GNRs was better with the NIR laser than without one, which combined photothermo- and chemo- effect.