| PFBT-Dox-Lip-FA was prepared in this research by encapsulating polymer dots of poly(9,9-dioctylfluorene-2,7-diylco-benzothiadiazole)(PFBT)and doxorubicin into the liposomes as well as modifying folic acid on the surface,which was aimed at achieving tumor visualizing and targeting therapy simultaneously.Firstly,the proportion of prescription and preparation method were selected and determined.Then,PFBT-Dox-Lip-FA hybrids were characterized in terms of morphology,particle size and electric conductivity.In the result,the morphology of liposomes was nearly spherical.AFM images confirmed the particle surface morphology of the liposomes modified with FA ligand.Particle size,Zeta potential and encapsulation efficiency of PFBT-Dox-Lip-FA was 127.30±3.20 nm,25.00±2.00 m V,and 89.5±4.6%,respectively.In addition,as compared to Dio-Lip-FA,PFBT-Lip-FA showed higher fluorescent intensity in the CLSM study,which indicated that PFBT was an ideal fluoprobe for theranostic liposomes.The drug release from PFBT-Dox-Lip-FA was enhanced as compared with Dox-Lip-FA at the same condition.Drug release from both formulations at 37°C was very slow,with only 46.35% and 31.78%,respectively.While at 42°C,the Dox release rate was much faster,with the significantly higher release approximately 84.87% and 73.62%,respectively.The cell viability assay and cellular uptake experiments were conducted on HepG2 cells and MCF-7 cells.Compared with Dio-Lip-FA,PFBT-Lip-FA did not introduce considerable cytotoxicity to the cells at the working concentration.More importantly,the PFBT-Dox-Lip-FA showed stronger cytotoxicity to MCF-7 cells,which IC50 was only 16.8±4.5 μg/m L.In cellular uptake experiments,the fluorescence intensity of PFBT was significantly higher than Dio,which confirmed the superior visible property of PFBT.Significantly stronger red fluorescence was detected in nuclei of PFBT-Dox-Lip-FA treated MCF-7 cells at different temperature(compared to those of HepG2 cells),which indicated the improvement of intracellular uptake of Dox.Similar phenomenon could be also observed in the time-dependent cellular uptake study.These results showed that MCF-7 cells effectively internalized the PFBT-Dox-Lip-FA by FR mediation.The in vivo imaging and anti-tumor growth experiments were conducted on MCF-7 tumor mouse model.In in vivo imaging experiments,PFBT-Lip-FA showed better detection in live animals compared with Dio-Lip-FA and Dox-Lip-FA.Therefore,PFBT could be used as a fluorescent maker for imaging-guided chemotherapy.In particularly,PFBT-Dox-Lip-FA combined with mild hyperthermia exhibited the highest inhibitory effects on tumor growth during the whole test time(up to 16 d),with the smallest tumor sizes(298.1±38.1 mm3)at the end of the study.More importantly,the treatment with theranostic liposomes combined with mild hyperthermia did not lead to any significant body weight loss,which might be due to their higher accumulation in tumor site and lower distribution in normal organs.With the high antitumor efficacy and the low drug-related toxicity,the theranostic liposomes were promising in cancer diagnose and targeting therapy.In summary,PFBT-Dox-Lip-FA can not only significantly increase the accumulation of doxorubicin in the tumor site,but also monitor cancer treatment process.It is expected to become a carrier for visualizing the treatment of tumors,and have a broad prospect in the application of anticancer drug delivery system. |
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