The Fabrication And Application Of Nanocarriers For Targeted Anticancer Drug Delivery

According to the physiological characteristics of the tumor environment,the artificial construction of nanocarrier with specific structures and functions,which can specifically target to tumor tissues,imaging and realize multiple therapeutic functions,will become the key to efficient cancer theranostics.Integrating the high specific surface area and selective penetration properties of hollow-mesoporous structure with the biocompatibility and various in vivo theranostic modalities of superparamagnetic iron oxide nanoparticles,to develop multimode molecular imaging diagnosis and combination therapy strategy of tumor,may provide important scientific basis and methodological reference to clinical personalized medicine based on nanotechnology.This research was focus on the preparation methods of hollow-mesoporous nanostructures and their applications as multifunctional drug carriers for imaging and photothermal-chemo combination therapy of tumors.1.Silica nanotubes?SNT?with hollow-mesoporous nature were designed and synthesized.SNT@Fe₃O₄ composite functional carriers were prepared by as established high temperature thermolysis route,using SNTs as templates.The superparamagnetic nanotubes exhibit satisfactory doxorubicin loading capacity and pH responsive release,high saturated magnetization value and good magnetic resonance imaging?MRI?contrasting effect.Specific targeting to cells overexpressing CD44?such as the mouse breast cancer 4T1 cells?was achieved by surface encapsulation with hyaluronic acid.After intravenously injected into mice,the carriers were significantly enriched in tumor tissues by receptor and magnetic field targeting mechanism,realizing MRI diagnosis and chemotherapy.2.The“yolk-shell”type GNR@IONPs nanostructures with inner space and intact mesoporous shell were obtained,by in situ deposition of iron oxide nanoparticles layer,surface encapsulation of mesoporous silica and selective etching of silica templates with gold nanorods?GNRs?,integrating near infrared photothermal conversion and quick magnetic responsiveness functionalities.The loading and stimuli?pH/NIR irradiation?-responsive release of doxorubicin was achieved by the mesoporous feature of iron oxide shell.After intravenously injected into tumor-bearing mice and magnetic field targeting,NIR photothermal therapy?reaching localized temperature of 55 ^oC?and chemotherapy were proceeded,realizing the complete tumor ablation.3.The self-polymerization of dopamine as a novel strategy of bio-inspired synthesis and surface modification of substrates,are showing great potentials in constructing functional and biocompatible nanostructures.Here we developed nanoscaled polydopamine template?PDA?and their derivated controllable ferroferric oxide layers by in situ deposition route via high-temperature thermolysis.This magnetic layer was encapsulated by a PDA shell by self-polymerization of dopamine under ultrasonication.The prodrug was synthesized by coupling both anti-cancer drug doxorubicin and amino-terminated homo-bifunctional PEG to a reduction-responsive linker.The PDA derivated theranositc nanocarriers were established by covalently linkage of the prodrugs to the sandwich structure surface,which showed reduction-responsive in vitro drug release.After intravenous injection of the nanocarriers into 4T1 tumor-bearing mouse,the MRI-PAI dual-modal tumor imaging was achieved,together with the combination therapy using both magnetic field targeting and near-infrared laser irradiation.In summary,the above research work provides the general assembly strategy of SPIONs and hollow-mesoporous silica materials,as also as the preparation of multifunctional nanomaterials.We have study there potential applications as tumor theranostics.Our work may provide important scientific basis and methodological reference for the design and development of effective nanotheranostics in the future research.