Preparation And Analysis Of Targeted Paclitaxel-liposome-microbubble Complex

Objective Targeted delivery of drugs by ultrasound targeted microbubble destruction had become a novel drug delivery method in cancer therapeutic application.However,the drug loading capacity of the lipid monolayer shell,which was difficult to reach the effective dose of tumor therapy.Here,we introduced a targeted liposome-microbubble complex: paclitaxelliposomes’ surfaces were modified by iRGD and which were connected with microbubbles.High drug loading of liposomes and controlled release properties of microbubbles were used for ultrasound molecular imaging-guided therapy of breast tumor.Methods Biotinylated iRGD modified paclitaxel-liposomes and Biotinylated ultrasound microbubbles were prepared by film-ultrasonic dispersion method and combined by Biotinavidin-system.The targeting effect in vitro was determined with adhesion efficacy experiments.The tumor model of subcutaneous breast cancer in mice was developed to determine the targeting effect in vivo via fluorescence intensity of drugs in tumor.Taking advantage of targeted delivery of drugs by ultrasound targeted microbubble destruction technology,we compared the anti-tumor effect of iRGD modified paclitaxel-liposome-microbubble complex in combination with ultrasound(iRGD-lipo-MBs+US)with nontargeted paclitaxel-liposomemicrobubble complex in combination with ultrasound(Control-lipo-MBs+US),iRGD modified paclitaxel-liposome-microbubble complex without ultrasound(iRGD-lipo-MBs)and microbubble in combination with ultrasound(MBs+US)in vivo.Results The average particle size of iRGD modified paclitaxel-liposome-microbubble complexes was(1.80 ± 0.26)μm,and drug loading of which was(46.22 ± 1.95)μg·10-8.Adhesion efficacy experiment in vitro showed that the quantity of complexes in targeted group was obviously more than in control group(7.8 ± 1.1,0.2 ± 0.45,P < 0.01);Accumulation of IR-780 in tumors of targeted group was higher than that of control group as determined by visualized fluorescence of in vivo imaging.After loading the theranostic drugs and combining with ultrasound irradiation,group(iRGD-lipo-MBs+US)showed significantly stronger antitumor effect in these tumor-bearing mice than that of group(Control-lipo-MBs+US),group(iRGD-lipo-MBs)and group(MBs+US),which was confirmed by histological analysis.Conclusions In summary,our study provided a novel targeted drug loaded liposomemicrobubble complex and which can be used not only for ultrasound molecular imaging,but also for targeted drug therapy of tumor.It would have a potential value to act as an ultrasound imaging probe for ultrasound image-guided tumor therapy.iRGD modified liposomemicrobubble complex,as a targeted drug delivery system,could integrate ultrasound molecular imaging and ultrasound-triggered therapeutic drug delivery to increase accumulation of drugs in tumors.