Construction And Anticancer Activity Of Multifunctional Nanocomposites

Photosensitizer(Ps)play a vital role in photodynamic therapy(PDT),In order to improve the therapeutic effect of PDT,the research on multifunctional photosensitizer has attracted considerable attention in recent years.Upconversion nano-materials(UCNPs)can be excited by near-infrared light(NIR)and emit high-energy photons in the range of visible light.The nano-materials can be used to excite the Ps molecules for PDT.Small molecular target-based anticancer drugs can specifically recognize the tumor cells.Zinc(Ⅱ)phthalocyanine is considered to be one of the most promising second-generation photosensitizers for PDT.Using the above functional moiety to construct multifunctional nano-system can give a multifunctional photosensitizer with tumor specifically,high photodynamic cativity and more depth treatment.This study can provide a reference for multifunctional photosensitizers development.Four multifunctional nanocomposites with UCNPs,ZnPc and small molecule target drug moiety were designed and prepared in this paper.The synthesis,photophysical and photochemical properties and photodynamic activity of these multifunctional nano-systems were investigated.The main works and results are summarized as follows:1.Two kinds of multifunctional nanocomposites ZnPc-UCNP-PEG-G(system 1)and ZnPc-UCNP-PEG(system 2),which with uniform size and high luminous efficiency,were synthesized by micro-emulsion method,then surface modified by the polyethylene glycol to achieve functional by binding with β-monocarboxylate substituted zinc phthalocyanine and binding the active domain of gefitinib,a small molecule targeting drug.The oil-soluble UCNPs was superwrapt with a layer of amino functional silicon dioxide,and then surface modified to obtain ZnPc-UCNP@SiO2-PEG-G(system 3)and ZnPc-UCNP@SiO2-PEG(system 4).2.The upconversion luminescence properties of the systems excited by near infrared were studied by fluorescence spectroscopy method.The fluorescence resonance energy transfer efficiencies of ZnPc-UCNP-PEG-G and ZnPc-UCNP@SiO2-PEG-G was 92.3%and 91.7%,respectively.The singlet oxygen yield(Φ△)was decreased by 40.7%and 15.9%under the irradiation of 980 nm,while the Φ△ decreased by 88.9%and 78.7%at 670 nm,when the systems was covered with 1 cm thick tissue.These indicated that both systems can increase the treatment depth of PDT.3.The results of the uptake of the title system by cells were showed that introduction of gefitinib moiety can increase the uptake of system by the tumor cells.The uptake amount of ZnPc-UCNP-PEG-G was 1.88 times that of ZnPc-UCNP-PEG and the uptake amount of ZnPc-UCNP@SiO2-PEG-G was 1.9 times that of ZnPc-UCNP@SiO2-PEG.By cell co-culture comparing the uptake of ZnPc-UCNP-PEG-G and ZnPc-UCNP @ SiO2-PEG-G with two cells,the ratios(HepG2/HELF)was 2.1 and 2.5,respectively.Determined by MTT method,the IC50 value of systems against the HepG2 cells,by irradiation of 670 nm,was 65.27μ/mL and 29.04 μg/mL for ZnPc-UCNP-PEG-G and ZnPc-UCNP@Si02-PEG-G respectively.In summary,ZnPc-UCNP-PEG-G and ZnPc-UCNP@SiO2-PEG-G improve the PDT treatment depth and tumor targeting of zinc phthalocyanine.They are expected to develop into a highly effective and low-toxicity anticancer drugs.