Safety-by-desgin And Biomedical Applications Of Nanomaterials Regulated By Propterty-activity Relationship

During recent years,nanomaterials have been widely used in biology,medicine,industry,and catalysis,which are closely related to their unique physical and chemical properties.The establishment of the property-activity relationship between nano-materials and biological systems can help us predict the potential hazards of nanomaterials,safe-by-design of nanomaterials for safer applications while not changing their functions.Based on the property-activity relationship,the mechanism of interaction between nanomaterials and organisms can be further understood.As a result,more biocompatible nanoparticles can be used for diagnosis,treatment and rehabilitation of diseases.We studied the molecular mechanism of biological effects induced by various nanomaterials,proposed the acquisition path of safe nanomaterials,and constructed a variety of nanosystems for photothermal and photodynamic therapy of cancer and promotion of wound healing process.The main research results are as follows:Firstly,different morphological Cu2O nanocrystals(octahedrons,truncated octahedrons,cuboctahedrons,and cubes)were synthesized to precisely tuning the{100} and {111} facet percentages in purpose of systematically investigating the toxicity role of crystallographic facets in BEAS-2B and RAW 264.7 cells.It was found that the toxicity of polyhedral Cu2O nanocrystals was highly dependent on the exposed {100} surface after short-term exposure because {100} facets could produce more reactive oxygen species(ROS)than {111} facets,however,after long-term exposure,their toxicity showed again the correlation with total surface property because toxic copper ions were largely released from the whole nanocrystal surface irrespective of {100} or {111} facet and this copper dissolution caused the collapse of surface crystals and the vanishing of ROS.Secondly,an electron compensation effect from Au to Ag was applied to design safe Au@Ag NPs.Ag shell thickness was precisely regulated to enable the most efficient electron enrichment in Ag shell,preventing Ag oxidation and subsequent Ag+ion release.As a result,a lower toxicological response than Ag NPs in different cells and mouse models was achieved.Further,Au@Ag NPs exhibit intense surface-enhanced Raman scattering signals,and were used for cell Raman imaging and in vivo Raman biosensing.Thirdly,three Au nanostructures,Au nanorods(NRs),nanoshells(NSs),and nanocages(NCs)with the same localized surface plasmon resonance(LSPR)peaks at 808 nm were prepared to compare the photothermal and photodynamic performance under the identical energy condition It was found that these Au nanostructures could induce similar levels of temperature elevation but different levels of ROS production,where Au NCs exhibited the highest ROS production,followed by Au NSs and NRs.In vitro and in vivo phototherapeutic assessments further supported that Au NCs could cause the most severe cell death and tumor growth regression owing to the comer angle structures of Au NCs.Fourthly,we designed two Au NCs microcontainers covered with different smart polymer shells(pH responsive and temperature responsive)containing Erl and Dox respectively.The acidic tumor microenvironment and NIR light irradiation can selectively activate the release of Erl and Dox.Time staggered release of Erl and Dox and photothermal therapy enhance the apoptotic signaling pathways,resulting in improved tumor cell killing both in vitro and in vivo.The photochemotherapy strategy controls the order and duration of drug exposure precisely in spatial and temporal,and significantly improves the therapeutic efficacy.Fifthly,sea urchin like gold palladium heterostructures(AuPd HSs)was synthesized for programmed acceleration of the multistages in wound healing process.AuPd HSs with strong nanobridge effect could rapidly closure of the wounds,promoting the hemostasis stage;Hot electrons in AuPd HSs could facilitate ROS production after exposed to the white light,inhibiting the bacteria growth;The sea urchin morphology of AuPd HSs could boosting macrophages polarize to M2 type,promoting the proliferation and maturation stages.