标题：pH- and Ultrasound-Responsive Paclitaxel-Loaded Carboxymethyl Chitosan Nanodroplets for Combined Imaging and Synergistic Chemoradiotherapy
作者：Shang, Mengmeng; Sun, Xiao; Guo, Lu; Shi, Dandan; Liang, Ping; Meng, Dong; Zhou, Xiaoying; Liu, Xinxin; Zhao, Yading; Li, Jie
作者机构：[Shang, Mengmeng; Sun, Xiao; Guo, Lu; Shi, Dandan; Meng, Dong; Zhou, Xiaoying; Liu, Xinxin; Zhao, Yading; Li, Jie] Shandong Univ, Qilu Hosp, Dept Ultr 更多
通讯作者地址：[Li, J]Shandong Univ, Qilu Hosp, Dept Ultrasound, 107 Wenhua Xi Rd, Jinan 250012, Peoples R China.
来源：INTERNATIONAL JOURNAL OF NANOMEDICINE
关键词：nanodroplets; ultrasound contrast agents; chemoradiotherapy;; radiosensitizer; paclitaxel; chitosan
摘要：Background: Synergistic chemoradiotherapy (CRT) has become a primary effective curative approach for many solid cancers. However, CRT is still associated with several obstacles, including the increases in side effects and systemic toxicity. Incorporating nanocarriers into CRT is a new and exciting approach to solve these obstacles. The purpose of the present study was to design a unique pH- and ultrasound-responsive perfluoropentane-encapsulated, paclitaxel (PTX)-loaded carboxymethyl chitosan nanodroplets (NDs) for combined imaging and synergistic CRT.; Materials and Methods: The NDs were prepared by a homogenization/emulsion method. Their physicochemical properties, echogenicity and biocompatibility were evaluated. PTX-loaded NDs with a high loading efficiency and encapsulation efficiency were prepared and their pH-responsive drug release profile was determined by dialysis sack method. Then, PC3 cells were exposed to (1) PTX (4 mu g/mL), (2) NDs (30 mu g/mL), (3) PTX-loaded NDs (34 mu g/mL), (4) RT (6 Gy), (5) RT (10 Gy), (6) combination of PTX (4 mu g/mL), ultrasound (0.5 W/cm(2), 30 s) and RT (6 Gy), (7) combination of NDs (30 mu g/mL), ultrasound (0.5 W/cm(2), 30 s) and RT (6Gy), (8) combination of PTX-loaded NDs (30 mu g/mL), ultrasound (0.5 W/cm(2), 30 s) and RT (6 Gy). 24 hrs later, CCK-8 assay, flow cytometry and migration assay were carried out to evaluate their therapeutic effects in CRT.; Results: The desired NDs were successfully prepared, which were with round, spherical shapes, relatively smooth surfaces, core-shell structures and uniform in sizes (<300 nm with PDI<0.3 when at pH >= 6.0). The NDs exhibited good abilities in pH-dependent charge conversion, biocompatibility and ultrasound contrast echogenicity. The in vitro drug release from PTX-loaded NDs (the highest loading efficiency and encapsulation efficiency were 20.35% and 91.58%) was pH dependent and exhibited an initial burst followed by a sustained drug release. The results of the CCK-8 assay, flow cytometry and migration assay all showed PTX-loaded NDs combined ultrasound and RT significantly enhanced cell responses in CRT.; Conclusion: The pH- and ultrasound-responsive PTX-loaded NDs, which exhibited a high echogenicity, drug delivery ability and radiosensitization ability, could be a feasible option for combined imaging and novel enhancing approach in synergistic CRT.