Drug Delivery Based On Functional Mesoporous Silica Nanoparticles For Cancer Bone Metastasis

Once bone metastasis occurs,the chances of survival and quality of life for patients decrease significantly.With the development of nanomedicine,nanocarriers loading bisphosphonates have been built to prevent cancer metastasis based on their enhanced permeability and retention(EPR)effects;however,as a passive mechanism,the EPR effects cannot apply to the metastatic sites because of their lack of leaky vasculature.In this study,we developed a drug delivery system based on MSNs for chemo-photothermal destruction of cancer bone metastasis.In the first part we fabricated 40 nm-sized mesoporous silica nanoparticles(MSNs)anchored by zoledronic acid(ZOL)for targeting bone sites and delivered the antitumor drug doxorubicin(DOX)in a spatiotemporally controlled manner.The DOX loading and release,bone-targeted ability,cellular uptake and mechanisms,subcellular localization,cytotoxicity and anti-migration effect of this drug delivery system were investigated.In the second part,CTAB-coated Au nanorods were firstly synthesized by the seed-mediated method.The Au@MSNs were synthesized via a single step coating method with TEOS and have two SPR bands,the longitudinal SPR band is at 808 nm,and the transverse plasmon band is at 530 nm.As-prepared Au@MSNs could be used as effective thermal generators owing to the Au nanorods ingredients.The photothermal effects depend on Au@MSNs concentration,laser illumination intensity and laser illumination time.Cellular uptake,subcellular localization,cytotoxicity,anti-migration effect and in vivo Photoacoustic imaging ability of this drug delivery system were investigated.This DDS is promising for the treatment of cancer bone metastasis in the future.