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This study was aimed to build a new photo-sensitive co-delivery liposomes which combine photodynamic therapy with chemotherapy to reverse drug resistance of breast cancer. Photodynamic photosen-sitizer chlorin e6 trimethyl ester (Ce6tM) and chemotherapeutic drug doxorubicin hydrochloride (DOX) were loaded into the liposomes (liposomes loaded with Ce6tM and DOX, CDL) by thin-film hydration extrusion and ammonium sulfate active loading methods. CDL was characterized with cryo-transmission electron microscopy (Cryo-TEM), dynamic light scattering particle size, zeta potentials and photo-sensitive DOX release behaviors in vitro. CDL cytotoxicity, singlet oxygen production, DOX accumulation, intracellular ATP level and cell cycle analysis in MCF7/ADR cells were evaluated. Finally, the tissue distribution of DOX and antitumor effects of CDL in BALB/c-nu nude mice bearing MCF7/ADR tumor were investigated. The results showed that the particle size of obtained CDL was 90.7 ± 1.1 nm and distributed uniformly. CDL possessed outstanding properties of photo-sensitive drug release profile. The accumulated release of DOX reached (96.52 ± 0.11)% in 2 min under 671 nm laser irradiation (2 W·cm-2). Interestingly, DOX in CDL could maintain rapid release after 671 nm laser irradiation with low power and short time (15 s, 0.25 W·cm-2). This phenomenon was caused by oxidation of unsaturated phospholipids in CDL under 671 nm laser irradiation and had nothing to do with the slightly elevated temperature. Photo-sensitive drug release behavior contributed to increased DOX accumulation in MCF7/ADR cells. The half inhibition concentration (IC50) of DOX in CDL laser group in MCF7/ADR cells was decreased by 601.9-fold compared with no laser group, which could be related to increased accumulation of DOX, decreased ATP levels and cell cycle arrest in MCF7/ADR cells. With the help of CDL, DOX accumulation in tumor was increased and in cardiac toxicity was reduced in vivo. CDL laser group showed a good anti-tumor effect. The tumor inhibition rate was (94.7 ± 6.2)%. These results suggest that CDL has a promising potential in reversing drug resistance of breast cancer.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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