Preparation, Characterization And Biological Applications Of The Nano-drug Carrier Based On Silica

Because of the low solubility, poor stability, side effect, easy to be fast metabolizedand cleared, lack of the functionality for targeting, some drugs have difficulty in playingefficacy during treatment. If the drugs are encapsulated in or modified on the surface ofdrug carrier, it can not only avoid the shortcomings of the drugs to a certain extent, butalso control the release of drugs, increase the biological membrane permeability, changethe distribution of the drugs in the body to make drugs accurate positioning, so as toimprove the utilization of the drugs. Enormous research efforts have been made todevelop ideal drug carriers with high loading capacity, better chemical stability,low-toxicity or non-toxicity, biodegradation, long circulation in the bloodstream, etc.Compared to the traditional organic-drug carrier, inorganic-drug carrier has higherloading capacity, better chemical stability and biocompatibility, which is more suitableto be a drug carrier. Mesoporous silica nanoparticles (MSN) attract more and moreattention due to their stable mesoporous structure, large surface area, large pore volume,good biocompatibility and the ability to be easily functionalized. In order to increase theloading capacity of MSN, many researchers dedicated to improve their structure inrecent years, especially enlarge their pore volume. It is the most effective method toexpand the loading capacity of MSN by introducing the hollow cavity in the interior ofMSN. Hollow mesoporous silica nanoparticles (HMSN) have all the advantages ofMSN, moreover, their cavity size and shell thickness are adjustable. Thus, it is easy tomodulate the loading capacity and the release of the drugs by changing the structure ofthe HMSN with no requirement of complex chemical modification.In this paper, we prepared HMSN with different methods and further did theresearch and application of HMSN in medicine and therapy. Based on this research direction, we carried out the following work:Chapter One: The application of the silicon nanocarrier in life science wassummarized in the first chapter. The preparation of HMSN and MSN and theirapplication as drug carriers were reviewed.Chapter Two: A series of HMSN with the same hollow and different shell or thesame shell and different hollow were prepared. CTAB was used as template agent andgold nanoparticles (AuNPs) as hard template during preparation. After that, CTAB wasremoved first by calcination and then AuNPs were removed by corrosion. So it can notonly remove CTAB completely, but also maintain the integrity of the hollow structure.The HMSN as-prepared are uniform, homogeneous-dispersed, low-toxic, with obviouscavity and adjustable structure, so they are well-behaved nanocarriers. We studied therelationship between the loading capacity as well as the release of anti-cancer drug (Dox)loaded in HMSN and the structure of nano-carrier. In addition, we studied the drugloading capacity of HMSN prepared with different process to eliminate template agent.The experimental results show that the drug loading capacity of HMSN and the drugrelease were related to the structure of the drug carrier, and the drug release is controlledby the thickness of shell.Chapter Three: HMSN were prepared by using silica nanospheres as hard template.Two kinds of single-stranded DNA valves which can hybridize with TK1mRNA andGalNAc-T mRNA respectively were coated on the surface of HMSN by electrostaticinteractions. TK1mRNA and GalNAc-T mRNA are two important tumor markers andoverexpressed in cancer cells. In cancer cells these two kinds of DNA will hybridizewith TK1mRNA and GalNAc-T mRNA respectively to form double-stranded DNA intheory, so the two DNA valves will open simultaneously and then the drugs will leak out.As some tumor markers are also overexpressed in normal cells, only one kind of DNAvalve may cause unexpected release of drugs. Two kinds of DNA valves should be ableto avoid the unexpected release of drugs effectively. Combined with the higher drugloading capacity and the better biocompatibility, HMSN will improve the therapeutic effect toward cancer cells greatly when the drugs are loaded into them. Furthermore, itmay cause little side effects to normal cells, which is very meaningful in cancer therapy.