کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10227192 429 2014 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dual sensitive and temporally controlled camptothecin prodrug liposomes codelivery of siRNA for high efficiency tumor therapy
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Dual sensitive and temporally controlled camptothecin prodrug liposomes codelivery of siRNA for high efficiency tumor therapy
چکیده انگلیسی
The combination of chemotherapeutic drug camptothecin (CPT) and siPlk1 could prohibit cancer development with combined effects. To ensure the two drugs could be simultaneously delivered to tumor region with high loading content, and the modulator siPlk1 could be released in advance to down-regulate the Plk1 expression to improve the sensitivity of CPT to cancer cells, dual sensitive and temporally controlled CPT prodrug based cationic liposomes with siPlk1 codelivery system was constructed. The pH-sensitive zwitterionic polymer poly(carboxybetaine) (PCB) was conjugated with CPT through pH and esterase-sensitive ester bond to enhance the stability and loading content of CPT. CPT-based cationic liposomes consisted of CPT-PCB prodrug and cationic lipid DDAB were then constructed for siRNA codelivery for combination therapy. The dual sensitive CPT-PCB/siPlk1 lipoplexes simultaneously delivered the two drugs to tumor cells and enabled a temporally controlled release of two drugs, that the siRNA was quickly released after 4 h incubation due to the protonation of PCB in endosomes/lysosomes, and CPT was released in a sustained manner in response to pH and esterase and highly accumulated in nucleus after 12 h incubation. The CPT-PCB/siPlk1 lipoplexes induced significant cell apoptosis and cytotoxicity in vitro with a synergistic effect. Furthermore, the dual sensitive CPT-PCB lipoplexes enhanced the tumor accumulation of the two payloads and exhibited a synergistic tumor suppression effect in tumor-bearing mice in vivo, which proved to be a promising delivery system for codelivery of CPT and siPlk1 for cancer therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 35, Issue 36, December 2014, Pages 9731-9745
نویسندگان
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