Constructions Of Sereval Inorganic Drug Nanocarriers With Good Biocompatibility For Anti-Cancer Applications

Cancer is a serious disease that endangers people's health.Although chemotherapy is the main methord to treat cancer,it is limited due to anti-cancer drugs' toxicity,poor selectivity,possibility of cancer recurrence and the induction of drug-resistant cancer cells.The growing studies confirmed that most of these limitations might be overcome using new nanotechnology-based tools nanoparticles because of their broad spectrum of unique physicochemical and biological features.Despite the fact that immobilization of anti-cancer agents on the surface of nanomaterials should improve their biocompatibility,it is confirmed that some nanoparticles can cause toxic effects in healthy cells.Therefore,the comprehensive and detailed analysis of physicochemical properties and safety profiles of nanomaterials must be performed before their introduction to further studies and clinical applications.Moreover,another important aspect should be also considered that the desirable drug carriers could be degraded into harmless and clearable products from the biologic system after they carry out the diagnostic or therapeutic functions.The biodegradable drug carriers can facilitate the surgical removal of carriers and reduce the damage caused by carrier accumulation.Additionally,despite the great potential of nanomaterials to treat solid tumors,the treatment of metastatic cancers is still challenging,since metastasized cells are too small to create microenvironment and EPR effect is less important.Based on the above problems,we designed three systems of drug nanocarriers for anti-cancer application:? Monodisperse and mesoporous walnut kernel-like silica nanoparticles?MSNs?with diameters about 100 nm have been synthesized by a templating sol-gel route.After an annealing process,the as-obtained sample?DLMSNs?inherits the well-defined morphology and good dispersion of MSNs,and exhibits bright white-blue luminescence,higher specific surface area and pore volume,and better biocompatibility.The drug loading and release profiles show that DLMSNs exhibit high drug loading capacity and an initial burst release followed by a slow sustained release process.Interestingly,the luminescence intensity of the DLMSNs-DOX system increases gradually with the increase of cumulative released anticancer drug doxorubicin?DOX?,which can be verified by the confocal laser scanning images.The drug carrier DLMSNs can potentially be applied as a luminescent probe for monitoring the drug release process.Moreover,the DLMSNs-DOX system exhibits potent anticancer effect against three kinds of cancer cells?He La,MCF-7,and A549 cells?.? The uniform and well-dispersed Y₂O₃:Yb³⁺,Er³⁺ hollow spheres?YOHSs?have been fabricated by a general Pechini sol-gel process with melamine formaldehyde colloidal spheres as template.The novel YOHSs with up-conversion luminescence has good drug loading amount and drug release efficiency.Moreover,it exhibits pH-responsive release patterns.In particular,the YOHSs sample exhibits low cytotoxicity and excellent degradable properties in acid buffer.After loaded with DOX,the antitumor result in vitro indicates that YOHSs-DOX might be effective in cancer treatment.The animal imaging test also reveals that the YOHSs drug carrier can be used as an outstanding luminescent probe for bioimaging in vivo application prospects.The as-obtained degradable drug carrier with up-conversion luminescence may enhance the delivery efficiency of drugs and improve the cancer therapy in clinical applications.? We have designed a miRNA loaded nanoparticle-based delivery system to co-regulate bone formation,bone resorption,and migration of breast cancer cell for the treatment of bone metastasis of breast cancer.Firstly,strontium doped hydroxyapatite?Sr/HAP?nanoparticles with different molar ratio of strontium synthesized by a hydrothermal method were evaluated their cell viability on mouse osteoblast cell line MC3T3-E1.The results show that 20% strontium doped hydroxyapatite?20%Sr/HAP?nanoparticles exhibit the best ability for cell viability and osteoblast differentiation on MC3T3-E1,mouse primary bone marrow mesenchymal stem cells.The similar results could be also found on bone repair in vivo.Moreover,the nanoparticle-based drug delivery system 20%Sr/HAP@CS@mi R34 a has been fabricated,which inhibits the formation of osteoclast-like cells and migration of breast cancer cells.This nanoparticle system may break the vicious circle of the microenviroment in bone and treat the bone metastasis of breast cancer.In summary,the results of this study show the basic data for the development of inorganic nanoparticle-based drug systems with good biocompatibility and the noval theraputic method for osteolytic bone metastasis of breast cancer,which is undoubtedly of scientific significance in the biomedical field.