کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6389 488 2013 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A pH-responsive α-helical cell penetrating peptide-mediated liposomal delivery system
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
A pH-responsive α-helical cell penetrating peptide-mediated liposomal delivery system
چکیده انگلیسی

Tumor-oriented nanocarrier drug delivery approaches with pH-sensitivity have been drawing considerable attentions over the years. Here we described a liposomal delivery system modified with pH-responsive cell penetrating peptide TH (TH-Lip). Conventional cell penetrating peptide (CPP)-related drug delivery tactics sometimes seemed limited due to the extensive in vivo penetration and the lack of proper selectivity of conventional CPPs. In this study, TH (AGYLLGHINLHHLAHL(Aib)HHIL-NH2), an engineered α-helical cell penetrating peptide originated from peptide TK (AGYLLGKINLKKLAKL(Aib)LLIL-NH2), was endowed pH-responsiveness after complete replacement of all lysines in the sequence of TK into histidines, and was introduced onto the surface of liposomes. Accordingly, TH-Lip could benefit from the unique property of TH, as the cell penetrating capacity of TH was concealed during the blood circulation and in normal tissues because of the neutral pH under those conditions. However, when TH-Lip reached the tumor, and as pH declined, histidines in TH peptide protonated and the surface charge of TH-Lip converted from negative to positive, initiating activated cell penetrating capacity and leading to enhanced cellular and tumor spheroid uptake. The endocytosis inhibition assay demonstrated that the endocytosis of TH-Lip was influenced by the positively charged surface of the liposomes in acidic environment and was mediated by clathrin, and the intracellular trafficking study suggested that the liposomes were mainly accumulated in endoplasmic reticulum and Golgi apparatus. After systemic administration in mice, TH-Lip could be internalized into tumor cells efficaciously. When it comes to the delivery of paclitaxel (PTX), the pH-responsiveness of TH-Lip led to strong inhibition against tumor cell growth which occurred both in vitro (under pH 6.3) and in vivo, and the tumor inhibition rate reached 86.3% on C26 tumor-bearing mice for PTX-loaded TH-Lip. Therefore, TH-Lip proved itself to be a promising pH-responsive strategy for drug delivery within acidified tumor microenvironment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 34, Issue 32, October 2013, Pages 7980–7993
نویسندگان
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