Design,Synthesis And Biological Applications Of Drug-controlled Release Systems Based On Gold Nanorods

Cancer is one of the serious diseases that endanger human health,and chemotherapy has always been one of the important treatments for cancer.However,the immediate release of traditional antitumor drugs,such as doxorubicin?DOX?,cisplatin,and paclitaxel,usually has serious systemic side effects because drugs can not only accumulate in tumor tissues but also be uptaken by normal tissues.In addition,unnecessary consumption of drugs by normal tissues can significantly reduce the therapeutic effect.Therefore,the development of controlled drug release systems is of great significance in oncology medical research.The controlled drug release systems that respond to stimuli,such as light,pH,temperature,and biomolecules,have become a hot topic.In contrast to other stimuli,near-infrared light?NIR?has the advantages of remote control,deep tissue penetration,and negligible phototoxicity,more intriguingly,NIR can be controlled by adjusting laser power,exposure time,and action site.The gold nanorods?AuNRs?have excellent NIR photothermal conversion properties,mature synthetic route,good biocompatibility and easy surface modification,which make them widely exploited for ion detection,bioimaging,drug delivery,and photothermal treatment.Therefore,the photo-responsive controlled drug release systems based on AuNRs are not only able to realize controlled drug release,but also can combine drug release with other tumor therapies to achieve synergetic effects.Hence,we conducted the following works:?1?Firstly,one-pot synthesis and seed preparation methods were used to obtain sAuNRs and AuNRs with different aspect ratios.And then uniform yolk-shell nanostructures were prepared,which were abbreviated as sAuNRs-YS and AuNRs-YS,respectively.The sAuNRs-YS and AuNRs-YS nanoparticles were characterized by transmission electron microscopy,high-resolution transmission electron microscopy,scanning electron microscopy and X-ray photoelectron spectroscopy.In addition,we explored the influencing factors and stability of AuNRs.During the fabrication of AuNRs-YS,we investigated the impact factors,such as etching methods,hydrothermal etching time and dosage of polyvinylpyrrolidone?PVP?.Finally,sAuNRs-YS and AuNRs-YS nanoparticles were successfully prepared for large-capacity drug loading.The cavity of AuNRs-YS nanoparticles is 26±3 nm.?2?A near-infrared photothermal-responsive bubble-generating theranostic nanoplatform was successfully designed and synthesized,abbreviated as DOX&ABC@Au NRs-YS.AuNRs serve as the photothermal core and a thin layer of silica acts as a shell,forming yolk-shell structure loaded with anti-tumor drugs and the bubble-generating precursor ammonium bicarbonate?ABC?as a NIR stimulus gatekeeper.Bubbles are yielded by the encapsulated ABC under hyperthermia,so that the co-encapsulated drug is released and drug concentration at tumor sites is swiftly increased along with the sabotage of DOX&ABC@AuNRs-YS.By investigating the feed ratio,the mass ratio of AuNRs-YS to DOX was selected to be 1:1.86,and through the study of drug release methods in vitro,the centrifugal release method is preferably selected and its drug release behavior is explored under different conditions including NIR laser irradiation,pH media and intracellular microenvironment.?3?DOX&ABC@AuNRs-YS nanocarrier is suitable and efficient for synergetic therapy at cellular and in vivo levels.Through evaluation of its cellular uptake pathway and cell cytotoxicity,it was determined that the nanocarrier could be safely applied at the cellular level,and the therapeutic effect of DOX&ABC@AuNRs-YS nanocarrier was further explored by confocal laser scanning microscopy?CLSM?and flow cytometry?FC?.The lower NIR laser irradiation(0.96 W·cm^-2)achieved 80.3%mortality of HeLa tumor cells.And the co-staining method was used to investigate the intracellular uptake pathway of DOX&ABC@AuNRs-YS.In addition,body weight and tumor size of the tumor-bearing mice were monitored in real time,H&E staining method was then used to determine the in vivo toxicity of the drug-controlled release system.The model of subcutaneous HeLa tumor in nude mice was used to further prove that the bubble-accelerating drug release nanocarrier DOX&ABC@AuNRs-YS,triggered by NIR light,exibited excellent therapeutic effect towards tumor,which shows promising prospect in tumor medicine.?4?The singlet oxygen carrier?NDE?was obtained by the use of naphthalene derivatives for the capture of singlet oxygen,and the large cavity of the yolk-shell structure was used.Meanwhile,NDE and the model drug DOX were loaded in the yolk-shell nanostructure,denoted as NDE&DOX@Au NRs-YS.Finally,the NDE&DOX@AuNRs-YS nanoparticles were successfully designed and fabricated.It is expected to achieve NIR light-triggered combined therapy of photothermal therapy,chemotherapy and photodynamic therapy.