Doxorubicin loaded micelles were prepared by film-hydration method using stearyl sulfadiazine (SA-SD) which is pH sensitive, methoxy (polyethylene glycol)-2000-1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine (mPEG-DOPE) and transactivator of transcription (TAT) peptide conjugated PEG-DOPE. Mean diameter of the pH-sensitive micelles was about 20 nm with a (99.1 +/- 2.1) % drug entrapment efficiency at pH 7.4. Flow cytometry studies revealed that the simple TAT micelles was taken up rapidly at the same level at pH 6.8 and pH 7.4. However, the pH-sensitive micelles entered the tumor cell less at pH 7.4 and significantly increase at pH 6.8. After 1 h incubation at pH 6.8, the amount of the pH-sensitive micelles taken up by cancer cell 4T1 was almost similar to simple TAT micelles. The confocal microscopy indicated that the pH-sensitive micelles entered the 4T1 cells at pH 6.8 more than at pH 7.4. It was indicated that the pH-sensitive micelles could shield TAT peptide at normal pH 7.4 and deshield it at pH 6.8. Hence, TAT peptides lead the drug-loaded micelles into the tumor cells and killed them selectively. The pH-sensitive micelle may provide a novel strategy for design of cancer targeting drug delivery system.

Objective:To analyze the clinical value of indocyanine green (ICC) fluorescence imaging in Mirizzi syndrome type Ⅱ-Ⅲ laparoscopic cholecystectomy (LC).Methods:A retrospective analysis was performed on 80 patients diagnosed with Mirizzi syndrome types Ⅱ-Ⅲ who underdoing LC in Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from October 2018 to February 2022, including 32 males and 48 females, aged (63.5±6.9) years. Patients were divided into two groups based on whether ICG fluorescence imaging technology was used, the control group ( n=38) that patients were treated with conventional LC and the experimental group ( n=42) patients were treated with LC guided by ICG fluorescence imaging. In the experimental group, the extrahepatic bile duct was identified by ICG fluorescence imaging during LC, and ICG was injected intraoperally to determine the reserved blood flow of gallbladder flap for fluorescence imaging and determine the resection line. Operation time, intraoperative blood loss, conversion rate of laparotomy and postoperative complications (bile leakage, incision infection, etc.) were compared between the two groups. Intraoperative fluorescence imaging and determination of the modified resection line of reserved gallbladder were analyzed in the observation group. Results:There was no significant difference in age, male proportion, type of Mirizzi syndrome and conversion rate of laparotomy between the two groups (all P>0.05). In the observation group, the operative time was (208.7±32.0) min, the intraoperative blood loss was (50.5±23.8) ml, and the biliary leakage was 7.1% (3/42), which was lower than that in the control group (228.2±33.9) min, (73.8±31.0) ml, 26.3% (10/38). The differences were statistically significant (all P<0.05). Of 37 cases (88%) showed common hepatic duct and common bile duct successfully in the observation group. In the observation group, ICG fluorescence imaging was used to determine the gallbladder resection line in 8 cases (19.0%). The gallbladder flap without fluorescence imaging was removed. Conclusion:ICG fluorescence imaging in LC for Mirizzi syndrome patients can identify the common bile duct and hepatic duct to guide surgical resection, determine the gallbladder flap resection line, reduce postoperative bile leakage and bleeding, and accelerate the surgical progress.