| PART Ⅰ CONSTRUCTION OF FE-LOADEDLIQUID-SOLID PHASE INVERSION PLGA IMPLANTSAND HEATING STUDY IN VITROObjective To prepare Fe-loaded liquid-solid phase inversion poly(lactic-co-glycolic acid)(PLGA) Implants, and to explore its potentialproperty on magnetic hyperthermia in vitro.Method Prepare three different filler fractions of Fe in the Fe-ISFIs(30wt-%,40wt-%,50wt-%). Then observe their process of liquid-solidphase inversion by ultrasonography and the inner structure of the solidswith scan electron microscope (SEM). In vitro, heat the solidified Fe-ISFIsin the alternating magnetic field and record temperature vs. time, fromwhich to choose the optimum filler fraction（40%） of Fe-ISFIs. In isolatedpork liver tissue,50ul of the chosen Fe-ISFIs were injected and also heatedin the magnetic field, of which temperature vs. time of the liver surfaceabove the injection point and temperature of the vicinity were recorded. After heating, the Fe-ISFIs were sent for SEM. Finally,50ul Fe-ISFIs with40%filler fraction of Fe were injected into the isolated bovine liver tissueand then the alternating magnetic field was applied for1min,2min,3min,and5min, respectively. The diameters of the ablated liver tissues wererecorded.Results The solidified Fe-ISFIs were hyperechogenic inultrasonography images and cellular inside showed by SEM. The in vitroheating experiment showed that the temperature increased over time, andthat of the Fe-ISFIs with50%filler fraction of Fe increased fastest，however, which were hard for injection, so the Fe-ISFIs with40%fillerfraction of Fe were chosen for further study. In the isolated liverexperiment, the temperature of the liver surface can reach about60℃anddecrease with distance. The mean ablated diameters of liver tissue withdifferent times showed,50ul of Fe-ISFIs within3min was1.18cm.Conclusions Fe-ISFIs in the alternating magnetic field are able toget a high temperature during a short time, which is a new kind material ofmagnetic hyperthermia and is hopeful to form a novel magneticthermotherapy for tumor. PART Ⅱ FE-LOADED LIQUID-SOLID PHASEINVERSION PLGA IMPLANTS FOR IN SITU MAGNETICHYPERTHERMAL ABLATION OF MCF-7HUMANBREAST CANCERObjective To prepare Fe-loaded liquid-solid phase inversionpoly(lactic-co-glycolic acid)(PLGA) Implants (Fe-ISFIs), and to studythe ablation efficiency on MCF-7human breast cancer.Method According to part I, Fe-ISFIs with40%filler fraction of Fewere chosen for the experiment of this part.3nude mouse bearing MCF-7human breast cancer were directly injected50ul Fe-ISFIs into the tumorsguided by ultrasound, heated in the alternating magnetic field for3min,and then were euthanatized, resected the tumors for TTC and HE staining.Another8nude mouse bearing MCF-7human breast cancer injected50ulFe-ISFIs in the tumors were divided into two groups, group I for treatmentin the alternating magnetic field for3min and group II without magneticfield. Then observe the tumors’ growth of the above nude mouse.Results TTC staining of tumor tissue showed parts of nude mouse’tumor were completely ablated, while still exist incompletely ablatedtumors. HE staining of the tumors demonstrated the coagulation, whichwere cells with pyknotic nuclei,or an absence of nuclei. In the observationof tumor growth, the tumors of group II grew well over time, while in group I, the ablated tumors fell off at1-2days after treatment and thengradually healed at about14days after treatment，about one month later,parts of whose tumors were disappeared, while a small parts of whosetumors were still residual.Conclusions Fe-ISFIs combined the alternating magnetic field areable to ablate SKOV3human ovarian cancer in short time, which could behopeful as a new kind of minimally invasive thermotherapy for tumor. |
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