Construction Of Gold Nanostar-based Photothermal Control Nanovehicles And Their Application In Cancer Therapy

Cancer is one of the major killer diseases in humans all over the world.In our country,the morbidity and mortality of cancer are on the rise year by year.Therefore,it has been urging to develop efficient therapeutic strategies for cancer treatment.In addition to traditional methods such as surgery,radiotherapy and chemotherapy,some emerging strategies for cancer diagnosis and treatment have been acknowledged in recent years.Among them,photothermal therapy as a typical physical method is well-known for its remarkable advantages,such as spatiotemporal controllability,little invasion and high efficacy.These merits are based on the well-designed photothermal therapeutic reagents with the capacity of targeting the tumor,responding to the irradiation of near-infrared light and in situ converting the light energy to heat in high-efficiency.Gold nanostar is a kind of gold nanoparticle with multiple anisotropic sharp branches thereby has high absorption cross-sections in visible and near-infrared light regions,which contributes the main part for making gold nanostar a good candidate for photothermal therapeutic reagent,apart from the other advantages such as easy synthesis,easy surface modification and good biocompatibility.Moreover,via loading of drugs or imaging agents and modifying with targeting molecules,gold nanostar is expected to extend its applications in integrated cancer therapies and in constructing theranostic platforms for precision medicine.In this dissertation,a series of these integrated therapeutic platforms based on gold nanostars were constructed for enhanced cancer treatment efficacy.(1)An integrated photothermal-chernotherapeutic platform featured with light-controlled drug release was realized by modifying cucurbit[7]urils supramolecules on gold nanostars.Cucurbit[7]urils,for one thing were used to improve the stability of gold nanostars,for another,were used to carry the drug camptothecin via the hydrophobic interactions between the drug and the cavity of cucurbit[7]urils.Furthermore,under the near-infrared light irradiation,gold nanostars would convert light into heat to trigger the camptothecin release from cucurbit[7]urils and finally generated ta synergistic therapeutic effect for killing cancer cells.(2)A gold nanostar-based multifunctional nanoprobe was designed to precisely regulate the apoptosis of melanoma cells and to monitor their apoptosis in situ.The probe was composed of gold nanostar,cell penetrating peptides TAT and Cy5-tagged caspase-3 specific peptides.The fluorescence of Cy5 was quenched due to the nanosurface energy transfer effect.Upon laser irradiation,the intracellular activated caspase-3 resulting from the photothermal effect of gold nanostar could cleave the substrate peptide,leading to a significant fluorescence turn-on with high sensitivity.Therefore,this versatile nanoprobe makes a good PTT agent for the activation of caspase 3 in cells and for the in situ reporting of cell apoptosis as well.Moreover,apoptosis could be regulated by adjusting the photothermal dose according to the feedback of caspase-3 imaging.(3)A photothermal immunotherapy strategy was established by combining photothermal reagent of gold nanostars with immunoadjuvant CpG for metastatic tumor treatment.The therapeutic effect for distant metastatic tumor was studied on animal tumor models.The immunogenic apoptosis of tumor cells induced by local photothermal treatment based on gold nanostars is supposed to produce tumor-related antigens in situ and release damage-associated molecular patterns,which will further activate the immune response to achieve effective remove of both primary tumors and distant tumors.