Based On The Construction Of Mesoporous Silica Nano-drug Carrier System And Its Anti-tumor Activity

Chemotherapy is one of the major therapeutic methods of cancer.However,conventional chemotherapy suffers the disadvantages of strong side effect,such as low drug bioavailability,inability to bypass biological carriers,and lack of specific recognition,which maybe cause failure in cancer treatment.Nanomaterials have been emerged as an effective tool for the diagnosis and treatment of cancer and widely used in biomedical field due to their unique physical and chemical characteristics.By loading the anticancer drugs in the hollow or absorbing the drugs on the surface,nanoparticles can effectively protect the encapsulated drugs from premature release and degradation,which can prolong the circulation half-life in the blood and reduce side effect.Mesoporous silica nanoparticle(MSN),an inorganic nanocarrier,has attracted great attention as a promising drug carrier owing to their large surface area,highly ordered pore structure,adjustable pore size and excellent biocompatibility.In this paper,mesoporous silica nanomaterials are used as drug carriers,combined with SDT and thermotherapy,and the following research works are carried out.(1)Antitumor studies of Hyaluronic Acid-modified mesoporous silica nanocarrierHyaluronic acid(HA)is a biodegradable,biocompatible and non-immunogenic glycosaminoglycan.HA can used as a targeting moiety for cancer therapy,because many types of tumor cells over-express HA receptors like CD44.The targeting drug delivery system can be achieved by modifying HA on the surface of the drug loading system.In addition,the degradation of the HA shell by HAase that is concentrated in the tumor environment results in the rapid extracellular release of drug.In this system,we had prepared a novel targeted drug delivery system in response to HAase at tumor sites,which MSN as nanocarrier,doxorubicin(DOX)as model drug and m-HA with different crosslinking degree were coated on the surface of MSN as a targeting ligand.The results showed the nanomaterials enable controlled release of loaded anticancer drugs in tumor environments after receptor mediated endocytosis and exhibited a high cytotoxicity against MDA-MB-231 cells.(2)Enhanced chemo-therapeutic effect facilitated by sonication of MSNSDT is a non-invasive therapeutic modality,which combine sonosensitizers and ultrasound(US)to initiate a specific sonochemical reaction to produce reactive oxygen species(ROSs),by H2O or O2,to kill cancer cells.Mesoporous silica nanoparticles(MSN)have been extensively explored as drug delivery system because of their good biocompatibility,well-defined mesoporous nanostructures with large surface area and high pore volume.As a core shell-MSN complex is designed to incorporate two separate depots:MSN based inner core for loading doxorubicin(DOX).Cross-linked methacrylated hyaluronic acid(m-HA)gel based outer shell as gate keeper and CD44 mediated tumour targeting.The nanosystem(DOX@MSN-HA)is expected to exhibit a considerable accumulation at the tumour site due to a combination of passive(the enhanced permeability and retention effect,EPR)and active(cancer cells overexpress HA receptor like CD44)targeting mechanisms.(3)Antitumor studies of cancer cell membrane-modified nanocarrier in synergistic antitumor therapyThe cancer cell membrane is a kind of natural tumor targeting material.By using cancer cell membrane as a gating molecule and meanwhile the fluidity of the cell membrane increases under the condition of heating,lipid fusion is achieved by the cell membrane and the cell membrane coated on nanoparticles.Finally,the loading system was released,the synergistic chemotherapy and thermotherapy were played,and the targeting effect of the drug carrying system on the tumor was realized.In this experiment,MSN was used as a nanocarrier to carry out doxorubicin(DOX)and indocyanine green(ICG),and the drug loaded nanoparticles were coated with cancer cell membrane.A new drug loading system DOX@ICG@MSN@cell was constructed.This mode of administration can achieve synergistic treatment of chemotherapy and photothermal.In addition,the cell membrane modified on the surface of the nanoparticles can be targeted by the drug delivery system,achieving the target release of the drug and the targeting therapy of the tumor.The results showed that compared with the single treatment mode,combined chemotherapy with DOX and ICG photothermal effect had better tumor killing effect.