Preparation And Biological Evaluation Of Near-infrared Laser Controlled Release Nanocarrier With Synergistic Chemo-and Photothermal Therapy

There are multiple urgent problems in the process of drug release from entering the body circulation to the target site,including:1)the drug is difficult to achieve precise control and release;2)the drug is not released in advance;3)the arrival target of nano-drug carrier cannot effectively control the release.The goal of drug delivery technology is to provide a safer,more effective and convenient means of drug delivery to improve the effectiveness of cancer treatment.In the past few decades,numerous drug delivery systems ranging from the nanoscale to the macroscale have been developed with different release patterns,such as pH,temperature,enzymatic hydrolysis as well as redox reaction,and so on.Among these various systems,drug release is thought to be passive and predetermined based on the micro-environment of tumors.Because of the individual differences in cancer patients,this single solitary release method that does not regulate the release rate may not always be applicable to cancer treatment,because the drug release rate is uncertain.Therefore,the ability to actively and continuously regulate the release of drugs,accurately determine location,time and dose size,will be more conducive to drug delivery and improve the efficiency of cancer treatment.The light-triggered release is a unique method because it can control the drugs release in vitro,and improve the therapeutic effect and reduce toxicity for normal tissue.However,for high-energy ultraviolet?UV?or visible light irradiation systems,the reduced tissue penetration and unavoidable cellular damage would hamper their potential use in medical field.Near infrared?NIR?light,by contrast,is better suited to biomedical applications because it has deeper penetrating tissue and less damage to living cells.For the above mentioned problems,We have designed a new kind of near-infrared light controlled release system of drug nanoparticles for synergetic chemo-and photothermal therapy,using gold nanorod as the core,outer coating mesoporous silica,and loading adriamycin in the mesoporous.The surface of mesoporous silica is modified by the condensation of acid alcohol with double C₁₂-branched near infrared?NIR?laser sensitive coumarin derivatives.Use of coumarin derivatives on oil-wet carbon chain(C₁₂)and C₁₆-HA molecules in oil-wet carbon chain(C₁₆)between C₁₆nonpolar force-HA closely adsorbed on the surface of carrier,close the oil film formed by the union of C₁₂2 and C₁₆6 closely within the limit of hydrochloric acid doxorubicin in mesoporous,hydrophilic and C₁₆-HA molecules in some extend hyaluronic acid in the mesoporous silica,make nanometer carrier has targeted to tumor cells receptors CD44expression of too much function.By means of the unique optical properties of gold nanorods,when nano drug carrier with receptor interaction into the tumor cell,excessive expression of CD44 receptors with NIR laser stimulate tumor tissue,nano drug carrier will happen this chain reaction:?1?nanometer carrier into the tumor,sealing of doxorubicin hydrochloride oil-wet membrane and membrane contact,make part of the oil film cracking cause hydrochloric acid doxorubicin molecules can be released into the tumor cells;?2?in the NIR laser that inspired the two-photon process,two-photon sensitive coumarin and ester bond rupture on the surface of the mesoporous silica,coumarin from the surface of the mesoporous silica,due to drug carrier lost close oil-covered doxorubicin hydrochloride molecule can be released into the tumor cell proliferation;?3?the tumor cells of acidic environment make the Si-O-into Si-OH?pKa=7?in the mesoporous silica,negative charge density decreases,mesoporous silica with positively charged doxorubicin hydrochloride between force is abate,accelerate the release of adriamycin;?4?nanomaterials are the kernel of gold nanorods high efficiency of the near infrared laser is converted into heat energy,cause tumor cell temperature increases,can improve the solubility of doxorubicin in microenvironment and accelerate its thermal motion,further enhance the release of adriamycin.The release of adriamycin was induced by the combination of the above three regulation methods,and the apoptosis of tumor cells was promoted by the synergistic effect of small molecule drugs and photothermal therapy.