Multimodal Nano-formulation Based On Hollow Prussian Blue And Its Application In Anti-tumor And Wound Repair

Nanomaterials have been widely used in tumor treatment and skin wound repair due to their unique photothermal properties,high drug loading,and multifunctional surfaces.Compared with the traditional drug delivery,the drugs that were loaded in nanomaterials and constructed a multi-modal nano-delivery system with multiple functions can reduce the biological toxicity of the drug,increase the half-life of the drug and improve the availability of the drug.Therefore,a multimodal nanoformulation based on hollow Prussian blue was developed for the combined treatment of tumors and the healing of chronic diabetic wounds in this paper.The details were as follows:(1)Construct nano-formulations based on hollow Prussian blue for the application of tumor starvation-photothermal-chemical combined therapy.Above all,the carboxyl group of 4-carboxyphenylboronic acid(CPBA)formed a coordination bond with ferri ion of hollow Prussian blue(HPB)to obtain HPB-CPBA,and then the chemotherapeutic drug doxorubicin hydrochloride(DOX·HCl)was adsorbed to HPB nanoparticles Internal orifice.Futher,the polyvinyl alcohol bridged with glucose oxidase(PVA-GOx)was coated on the surface of the hollow Prussian blue by forming boronate dynamic covalent bonds.Finally,the hyaluronic acid bridged with aminobenzenboric acid(HA-APBA)was covered the outermost layer,by forming a boronate dynamic covalent bonds with polyvinyl alcohol,and the tumor nanoparticles(HDPG-HA)with active targeting and combined starvation-photothermal-chemical therapy were prepared.In vitro and in vivo experiments proved that HDPG-HA had a sensitive DOX release behavior with glucose-responsive,and GOx loaded on HDPG-HA can effectively decompose excess glucose in the tumor microenvironment to produce starvation therapy.Further,HDPG-HA exhibited good photothermal properties under near-infrared light irradiation.In addition,the HA molecules on the surface of HDPG-HA can also bind to tumor cells overexpressing CD44 receptors on the surface,which the nanoformulations had active targeting effects.Finally,we demonstrated that HDPG-HA had excellent tumor suppressive effect and good biosafety in vivo through triple-negative breast cancer mouse model.(2)Application research of composite nano-formulation based on hollow Prussian blue for diabetic skin wound repair.First,Hollow Prussian blue(HPB)was coated with a layer of 4-carboxyphenylboronic acid(4-CPBA)modified polylysine(EPL-CPBA),and then polydeoxyribonucleotides(PDRN)was electrostatically adsorbed onto HPB,then the polyvinyl alcohol bribed with catalase(PVA-CAT)was coated on the surface of hollow Prussian blue through the formation of boronate dynamic covalent bonds.Finally,the hyaluronic acid bridged with aminobenzenboric acid(HA-APBA)was covered the outermost layer,by forming a boronate dynamic covalent bonds with polyvinyl alcohol,and the nano-formulations(HPB@PDRN-CAT-HA)were prepared.The PDRN loaded in HPB@PDRN-CAT-HA had the effect of promoting fibroblast proliferation and angiogenesis,and the EPL layer coated on HPB also had the effect of inhibiting the growth of bacteria on the wound surface.Further,the CAT immobilized on the preparation can also effectively decompose the highly expressed reactive oxygen species(ROS)in the process of wound repair and improve the speed of wound healing.Finally,we comprehensively evaluated the wound repair effect of HPB@PDRN-CAT-HA by constructing a wound model of diabetic mice,proving that HPB@PDRN-CAT-HA had excellent anti-inflammatory,antibacterial effects on wounds and promote wound healing.