| Lignin is a biodegradable renewable raw material with great adsorption properties,biodegradable and non-toxicity.Through the morphology structural control of lignin,a new hollow lignin-based nanomaterial with both lignin and nanomaterial characteristics is constructed,which is one of the effective ways to utilize high value of lignin resources.The lignin-based hollow nanospheres have great application potential in the fields of drug delivery,tracer labeling and catalytic loading for the properties of large specific surface area,simple preparation methods,and easy surface multi-functional modification.Cancer is a critical public health problem worldwide,threatening human health.The nano drug carriers is an important part of tumor treatment for efficiently carry and transport anti-tumor drugs,realize targeted drug delivery and controlled release,and reduce the side effects of drugs.In this paper,enzymatic hydrolysis lignin-based hollow nanospheres is the development object to study the effect of the size and structure of nanospheres on its drug-loading properties.Additionally,β-cyclodextrin/lignin hollow nanospheres with high loading and sustained release capacity,fluorescent modified lignin hollow nanospheres and dual-targeted lignin hollow nanospheres were prepared.Different lignin-based drug delivery systems were constructed to achieve efficient drug loading,molecular tracking targeted delivery,showing good inhibition effect on cancer cells.The main research results were summarized as below:The lignin-based nanoparticles with particle size range of 200-600 nm and different shell thickness were prepared by studying the effects of initial lignin concentration,deionized water droplet acceleration and stirring speed on the size and structure.Besides,the effects of nanospheres with different morphology structures on the loading and release properties of doxorubicin were investigated.The results showed that the nanospheres were able to maintain dimensional stability in PBS（pH = 7.4）within 5 days at 37 ℃.The drug loading and encapsulation efficiency of hollow nanospheres increase with the increase of specific surface area and pore volume,and the sustained release capacity of drug-loaded particles increases with the increase of the wall thickness of the shell.An amino group was first introduced into the lignin molecule,and then the β-cyclodextrin monomer with hollow barrel structure was grafted onto the enzymatically hydrolysisi lignin by a sulfonylation reaction,and finally β-cyclodextrin/lignin hollow nanospheres obtained via self-assembly.The β-cyclodextrin/lignin hollow nanospheres have an average diameter of about 220 nm.And they were able to be stably stored in PBS（pH = 7.4）for 6 days at 37 ℃.Compared with the nanospheres prepared by pure enzymatic hydrolysis lignin,surface area and pore volume of this nanospheres were 23% and 22% higher,respectively.And the drug loading and encapsulation efficiency of β-cyclodextrin/lignin hollow drug-loaded nanospheres to HCPT can reach 70.6±9% and 22.02±2%,respectively.The results of in vitro cell experiments show that the nanospheres were not only non-toxic,but also had an excellent sustained release capability due to the increased the site of interaction with drugs.Fluorescent lignin-based hollow nanospheres with both diagnostic and therapeutic functions were prepared by a combination of amidation and self-assembly.Compared with the nanospheres prepared by sonication,the hollow nanospheres have stable size and controllable structure,and its suspension has better colloidal property.The particles were able to maintain the dimensional integrity of the solution within 15 days.And at the same concentration,the hollow nanospheres have higher fluorescence intensity.In addition,the Fluorescent lignin-based hollow nanospheres have a relatively hydrophobic shell and a relatively hydrophilic core structure,which contribute to the loading of the hydrophilic molecular drug doxorubicin hydrochloride.The encapsulation efficiency and the drug loading can reach 50% and 10%,respectively.Dual-targeted lignin-based hollow nanospheres were prepared by layer-by-layer self-assembly to modify Fe3O4 nanoparticles and folic acid molecules to the surface of lignin-based hollow nanospheres.The results show that Fe3O4 nanoparticles and folic acid molecules were uniformly coated on the surface of nanospheres.After modification,the average diameter of nanoparticles were 324±12 nm,and the structure was unchanged and the stability was enhanced.The functional nanospheres were superparamagnetic with a saturation magnetization of 10.25 emu/g.In vitro cell experiments confirmed that the dual-targeted lignin-based hollow nanospheres were more easily endocytosed by HeLa cells for their excellent active targeting ability.It has a good prospect in cancer treatment as the inhibition of cell proliferation was stronger under the same conditions. |
