Study On Docetaxel/IR820-loaded Liquid Fluorocarbon Nano-system Coated With Hydroxyapatite

The nanosystem combining diagnosis and treatment function can guide the progress of treatment in real time and provide a basis for the next treatment plan,which can improve the efficiency of tumor treatment,reduce the number of administrations,and decrease the toxic and side effects.In this study,we have prepared a novel multi-functional drug-loaded nanosystem(DTX-PFH-IR820@SL@HAP)which contains a soybean lecithin(SL)-perfluorohexane(PFH)nanodroplet core loaded with IR820/docetaxel(DTX)and a hydroxyapatite(HAP)shell.DTX-PFH-IR820@SL@HAP has many functions,such as chemotherapy,photothermal therapy(PTT),photodynamic therapy(PDT),ultrasound(US)imaging and photoacoustic(PA)imaging,making integration of cancer diagnosis and treatment possible.This study prepared the nanosystem and evaluated its functions in the following three chapters.Chapter one was the preparation and evaluation of DTX-PFH-IR820@SL@HAP.Objective: To Prepare DTX-PFH-IR820@SL@HAP and to characterize the physical and chemical properties of the nanosystem.To evaluate the photothermal effect,photodynamic effect,in vitro US imaging and PA imaging functions of the nanosystem.Methods: DTX-PFH-IR820@SL@HAP was prepared and related parameters and functions were investigated.Results: The results of transmission electron microscope showed that the prepared DTX-PFH-IR820@SL@HAP was nearly spherical.The particle size was 247.0 ± 1.9 nm and the zeta potential was-22.57 ± 1.15 mV.The drug load of DTX was 32.55% and the encapsulation rate was 92.01%.The drug load of IR820 was 3.67% and the encapsulation rate was 82.70%.The cumulative release of DTX in DTX-PFH-IR820@SL@HAP after 96 h was 71.26 ± 2.34%,which increased to 78.15 ± 3.04% after NIR excitation.The photothermal conversion efficiency of DTX-PFH-IR820@SL@HAP would increase as the concentration of the equivalent IR820 or power density increased.DTX-PFH-IR820@SL@HAP could produce photothermal effect and photodynamic effect under NIR irradiation,and also realized US imaging and PA imaging.Conclusion: DTX-PFH-IR820@SL@HAP was successfully prepared with good physical and chemical properties.The nanosystem had photothermal effect,photodynamic effect,as well as in vitro US imaging and PA imaging functions.The second chapter was the in vitro cell experiment of DTX-PFH-IR820@SL@HAP.Objective: To evaluate the cytotoxicity of DTX-PFH-IR820@SL@HAP on 4T1 cells.To verify the combined application of PTT,PDT and chemotherapy of DTX-PFH-IR820@SL@HAP in vitro.Methods: The MTT method was used to evaluate the cytotoxicity of different concentrations of nanosystem.The cells were divided into control,laser only,DTX,DTX + laser,DTX-PFH-IR820@SL@HAP,PDT and PDT + PTT groups to verify the cell killing ability.Results: The cytotoxicity of DTX-PFH-IR820@SL@HAP on 4T1 cells increased with the increase of equivalent DTX concentration.The combination of chemotherapy,PTT,and PDT had the strongest killing ability to 4T1 cells.Conclusion: DTX-PFH-IR820@SL@HAP could kill 4T1 cells through combined PTT,PDT and chemotherapy.The third chapter was the in vivo animal experiment of DTX-PFH-IR820@SL@HAP.Objective: To verify the US imaging and PA imaging capabilities of DTX-PFH-IR820@SL@HAP,as well as the effect of suppressing tumors in vivo.Methods: In vivo US imaging experiments,PA imaging experiments and tumor suppression experiments were conducted.Results: Compared with the control group,the DTX-PFH-IR820@SL@HAP group could detect obvious US and PA imaging signals in vivo.The tumor volume in the group which combined chemotherapy,PTT and PDT had decreased while the tumor volume of other groups increased.Conclusion: DTX-PFH-IR820@SL@HAP had US imaging and PA imaging capabilities in vivo,and could inhibit the tumor growth through a combination of PTT,PDT and chemotherapy.