Document Detail


Design of Acid-activated Cell Penetrating Peptide for Delivery of Active Molecules into Cancer Cells.
MedLine Citation:
PMID:  21663318     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
TP10-5 (TK) was screened as the most promising candidate among the designed analogs of transportan 10 (TP10), a cell penetrating peptide (CPP) with remarkable capacity for membrane translocation. However, low levels of specificity and high toxicity limit its successful use for drug delivery applications. Here, we developed a new type of acid-activated CPP (TH) by replacement of all lysines of TK with histidines. As expected, histidine-containing TH can be activated and subsequently enter cells at pH 6.0, whereas it is less active at pH 7.4. In contrast, the uptake of TK has no significant difference for both pH values. Importantly, the toxicity of TH was significantly lower than that of TK under physiological conditions. After attachment of camptothecin (CPT) to TH, this conjugate inhibited the proliferation of cancer cells in a pH-dependent manner compared with free CPT and TK-CPT. This study opens a new avenue to design CPPs that preferentially enter cells in acidic solid tumors, with minimal cellular uptake in normal tissues.
Authors:
Rui Wang; Wei Zhang; Jingjing Song; Bangzhi Zhang; Liwei Liu; Kairong Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-13
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  -     ISSN:  1520-4812     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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