Anti-tumor Study Of Epirubicin-Loaded Suerparamagnetic Iron-Oxide Nanoparticles(EPI-SPION) By Transdermal Delivery

Skin cancer is the most common malignancy in humans,with more than one million new cases each year,especially in light-colored race,where the incidence of skin cancer is increasing.Traditional chemotherapy and radiotherapy generally exist low target drug concentration,drug side effects and other defects.Thus,skin tumor,such as cutaneous malignant melanoma(CMM),is still lack of effective treatment methods.In the nano-drug anti-tumor study,magnetic targeting drug delivery system is generally used intravenously,requiring particles can freely go through the smallest capillaries,which lead to increased adverse systematic toxicity.In addition,the design and implementation of the magnetic field device for magnetic drug targeted therapy is also a key problem.This study att.empts to overcome these limitations by using a transdermal drug delivery system to explore new ways for skin tumors treatment.At present,the study of superparamagnetic iron oxide nanoparticles(SPION)has made great progress,from its initial focus on development for MRI imaging to the current 'target drug delivery,treatment and angiography.With its potential in MRI diagnosis,hyperthermia and targeted drug delivery,SPION is a hot topic in targeted drug research.In this study,?-Fe2O3 nanoparticles with functional groups were used as the core and epirubicin(EPI)as the tumor chemotherapeutic agent with carbonyl group was grafted onto it to obtain nano-particles with superparamagnetism(EPI-SPION).The mechanism and dynamic behavior of superparamagnetic nanoparticles transdermal absorption targeting tumor cells were discussed from the aspects of tumor drug therapy,molecular biopharmaceutics and material chemistry,to provide new ideas and explore a new transdermal delivery system technology.Firstly,functionalized ?-Fe2O3 nanoparticles were prepared by coprecipitation-crosslinking method.The particle size of the modified EPI-SPION SPION was 16 ± 2 nm,and the main physical and chemical properties showed that the nanoparticles had a spherical single domain lattice morphology,good magnetic performance and excellent superparamagnetic properties,with saturation magnetization greater than 70 emu/g.The EPI-SPION showed good magnetic responsiveness under the external magnetic field(intensity 280 mT).Almost all SPION particles dispersed evenly in the suspension showed a tendency to settle toward the magnetic field side.EPI-SPION has obvious acidic pH-responsive drug release characteristics,that is,in the normal tissue pH(about 6.8-7.4)conditions,12 h drug release less than 50%,and acidic pH 5.5-6.5 conditions,2 h drug release more than 55%.The trigger pH point was about 4.8.This pH value is close to the acidity of tumor tissue(pH4.7)and lysosomes(pH4.0-5.0).This important feature is very beneficial for the drug to exert its cytotoxic effect on local tumor cells.In the critical in vitro transdermal study,it was confirmed that SPION could overcome the normal cuticle barrier of the human body and transmit the drug to the deep dermis layer under the external magnetic field,thus realizing the effect of accumulating to the local tumor tissue.In fact,compared with the microenvironment of normal tissue,solid tumor tissue is rich in blood vessels and the vessel wall space is wide and the structural integrity is poor and lack of lymphatic vessel,resulting in granular and macromolecules with selective high permeability and retention,namely EPR effect(enhanced permeability and retention effect).In further cellular uptake study,SPION was incubated with human melanoma cell line WM266 and human immortalized epidermal cell HaCat.Fluorescence microscopy was performed to observe the cell uptake and drug release of EPI-SPION.The effect of EPI-SPION on the proliferation of WM266 melanoma cells and the biocompatibility of WM266 cells and HaCat cells were investigated by CCK8 method.The results showed that EPI-SPION could enter into WM266 cells and release EPI in tumor cells.In this process,H+ might be an important molecular switch affecting the release process.EPI-SPION could significantly inhibit the proliferation of WM266 cells in a concentration-dependent manner.The unloaded SPION had no effect on the survival and proliferation of HaCat cells,and showed low cytotoxicity to human epidermal HaCat cells.Even SPION with minimal concentration(Iron content of 1000[?g/mL)incubated for 24 h,the cell viability is more than 70%.In this study,multidisciplinary research ideas and techniques were used to define the mechanism of SPION targeting profiles and its delivery of broad-spectrum antitumor drugs to skin tumors.The effects of SPION on tumor growth were evaluated by magnetic regulation,biocompatibility,in vitro targeting,pharmacodynamics and pharmacodynamics.The magnetic-field-assisted SPION transdermal vector can circumvent the stratum corneum via follicular pathways.The study indicates the potential of a SPION-based vector for feasible transdermal therapy of skin cancer.