Preparation Of Multifunctional Nanoparticles And Their Application In Photodynamic/photothermal Tumor Therapy

Photodynamic therapy(PDT)and photothermal therapy(PTT),two promising noninvasive anticancer treatment,are currently being intensively studied as an alternative method to conventional cancer therapies.However,PDT and PTT still face certain problems in clinical applications.Firstly,the efficacy of PDT is largely compromised by(?)tissue hypoxia which inhibits the generation of singlet oxygen(1O2)by insufficient supply of oxygen and(?)the aggregation of photosensitizers in biological environments.Secondly,many researches have demonstrated that mono-PTT is not as effective as expected in eradicating tumors because of the inhomogeneous heat distribution within tumor tissue.Furthermore,the low quantum yield and photobleaching of ZnPc molecules restricts their fluorescence imaging to cellular level for further solid tumor located.In order to overcome these obstacles,a type of nanocarrier for MRI and synergistic PDT&PTT was reported in this work.The nanoparticle consists of a porous polymeric core encapsulating the photosensitizer ZnPc and photothermal agent magnetic Fe3O4 NPs,and further coated with a poly-L-lysine(PLL)shell(designated as ZnPc/Fe3O4@PLL)by electrostatic adsorption.On this basis,the as-synthesized NPs were investigated in terms of size,morphology,zeta potential,optical and magnetic properties respectively.The yield of 1O2 and photothermal conversion effect of ZnPc/Fe3O4@PLL were also determined.Based on the dual-functional NPs,in vitro cellular uptakes,PDT,PTT and synergistic PDT&PTT was carried out.The main findings of this paper are summarized as follows:1.ZnPc/Fe3O4 co-loaded NPs with a hydrodynamic size of?145 nm were prepared by a modified reprecipitation-encapsulation method.The optimum doping concentrations of ZnPc and Fe3O4 NPs were 4 wt%and 30 wt%,respectively.The aggregation degree of ZnPc in hybrid NPs was found to be considerably meliorated with the presence of Fe3O4 NPs,corresponding to higher 1O2 generation rate and photodynamic therapy efficiency.2.Based on the magnetic property of Fe3O4 NPs,ZnPc/Fe3O4@PLL hybrid NPs can be easily collected from aqueous solution with a magnet.ZnPc/Fe3O4@PLL exhibits excellent T2 magnetic resonance imaging contrast performance(a r2 relaxivity value of 152.9 mM-1 s-1).The temperature of the NPs solution during the 808 nm irradiation(4.43 W/cm2,5 min)rose rapidly by 34.4?,indicating the great photothermal conversion ability.3.ZnPc/Fe3O4@PLL has good biocompatibility,low dark cytotoxicity,high cell internalization efficiency(complete phagocytosis by cells after 4 h incubation),and good PDT?PTT combination therapy.