Preparation Of Multifunctional Drug-delivery Systems Based On Lanreotide Acetate And Study Of Biological Activity

On the cancer therapy,the combination of chemotherapy and other treatments has become a new research hotspot,which can not only effectively,but also avoid damage to normal tissues enhance the anti-tumor effect.In this study,inspired by biomineralization,we have bionic synthesized of light-responsive noble metal nanomaterials by using lanreotide acetate(Lan)as a template,and then the chemotherapeutic drug doxorubicin(DOX)was loaded on their surface.The synthesized nanocomposites can achieve both chemotherapy and hyperthermia,and then the antitumor effects of them are systematically studied.Herein,a novel bimodal drug system was assembled,based on a polydopamine(PDA)/doxorubicin(DOX)modified lanreotide acetate-gold nanoflowers(Lan-AuNFs@PDA/DOX).The Lan-AuNFs@PDA/DOX exhibited uniform morphology,excellent biocompatibility and photothermal conversion efficiency,which also could respond to stimulus including NIR light and pH to trigger on demand release of loaded drug.Moreover,under NIR laser irradiation,the heating effect induced by Lan-AuNFs@PDA/DOX can not only trigger photothermal therapy(PTT)to kill cancer cells directly,but also improve the chemotherapy effect by increasing drug penetration and uptake.Under NIR irradiation,the bimodal tumor inhibition ratio of the Lan-AuNFs@PDA/DOX was 91.75%,compared with chemotherapy(39.7%)or PTT(71.8%)alone,showing a superior synergistic therapeutic effect.The pronounced anisotropy endows excellent photothermal conversion efficiency of branched palladium nanoparticles(Lan-PdNPs),which was synthesized by biomimetic synthesis.Subsequently,DOX was loaded on the surface of the carrier by glutathione(GSH)to synthesize a multifunctional nano drug carrier(Lan-PdNPs@GSH/DOX)with uniform morphology and good biocompatibility.The connection between the drug and the carrier can be eliminated under the stimulation of NIR and pH,which enables the release of drugs on demand.Under laser irradiation,Lan-PdNPs@GSH/DOX rapidly generates a large amount of heat,killing tumor cells by PTT,and the heat makes tumor cells more sensitive to chemotherapeutic drugs to enhance the chemotherapeutic effect.The Lan-PdNPs@GSH/DOX possesses the abilities of hyperthermia and chemotherapy,showing a better synergistic anti-tumor effect and the tumor inhibition rate up to 90.33%.Therefore,this study designed and synthesized a multistimuli-responsive chemo-photothermal synergistic drug vehicle to achieve efficient antitumor by the synergistic effect of hyperthermia-chemotherapy,and have no damage to normal tissues,which provides a new possibility for the application of nanomaterials in the field of cancer therapy.