The Construction And Anti-osteosarcoma Performance Of Drug Coated Functionalized Titanium Oxide Nanorods Array

Osteosarcoma is the most frequent primary malignant bone tumors with high incidence and mortality during childhood and adolescence.The current approach to treat osteosarcoma is replacing cancerous bone with an orthopedic implant followed by chemotherapy or radiation therapy.However,there is still a risk of tumor recurrence and metastasis after the surgery due to the latency of cancer cells,and the patients usually require secondary surgery and a delay in recovery.In addition,the clinical chemotherapy drugs with low targeting frequently have side effects on normal tissue cells and result in long-term chemoresistance,which greatly reduces the patient's life quality.In order to improve the therapeutic effect of tumors and prevent post-operative recurrence of osteosarcoma,it is essential to explor novel anti-tumor drugs and functional biomaterial.This paper through the nano-topological structure design and surface biochemical modification to engineer titanium surface,and obtained bone substitute materials with anti-cancer properties and good compatibility.The main contents were as follows:(1)We first synthesized chitosan-18?-glycyrrhetic acid conjugate by esterification reaction,and fabricated Ti02 nanorods using a seed-assisted hydrothermal approach.Then we further functionalized TiO2 nanorods surface with polydopamine film for covalent grafting of chitosan-18?-glycyrrhetinic acid conjugate.The biological tests indicated that the chitosan-18?-glycyrrhetic acid conjugate modified TiO2 nanorods substrates efficiently inhibited the proliferation and induced apoptosis of osteosarcoma cells(MG63)in vitro,and significantly suppressed the osteosarcoma growth in vivo.In addition,the biocompatibility tests indicated that this modified surface significantly promoted osteoblast(MC3T3-E1)adhesion and proliferation due to the nanoarray structure stimulation and chitosan supplementation.Our investigation demonstrated the antiproliferative and apoptotic effects of 18?-glycyrrhetic acid on MG63 cells,this discovery provided evidence for 18?-glycyrrhetic acid as a new anti-osteosarcoma agent,and highlighted the potential application of traditional Chinese herbal medicines for cancer therapy.(2)We prepared a polydopamine-mediated TiO2 nanorods surface by the self-polymerization of dopamine,and a cyclodextrin polymer was further covalently grafted on its surface acting as a drug molecule-loaded and controlled-release carrier.In order to endow titanium-based implant with antitumor property,curcumin was loaded by the inclusion complexation of cyclodextrin.The biological tests indicated that the curcumin-modified surface in a concentration-dependent manner inhibited the adhesion and proliferation of osteosarcoma cells(MG63),decreased cell viability,and induced apoptosis.In addition,the curcumin-modified composite material did not show adverse effects on osteoblast(MC3T3-E1)adhesion and spreading,but inhibited the osteoblast proliferation.However,at the same curcumin concentration,the inhibition of samples toward osteosarcoma cells was significantly greater than toward healthy osteoblast.Considering its anti-tumor effect and biocompatibility,TiO2/pDA/pCD/CUR0.8 was an optimal candidate,which could inhibit osteosarcoma growth without affecting osteoblast activity.In summary,these two titanium-based implants with balanced anti-cancer properties and good biocompatibility could not only effectively inhibit tumor recurrence,but also promote the growth of healthy tissues,which was a potential candidate for bone transplantation to treat osteosarcoma and regenerate bone defects.