Design of Acid-Activated Cell Penetrating Peptide for Delivery of Active Molecules into Cancer Cells
Year: 2011
Type: article
Abstract: TP10-5 (TK) was screened as the most promising candidate among the designed analogues 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 is significantly lower than that of TK under physiological conditions. After attachment of camptothecin (CPT) to TH, this conjugate exhibited remarkable cytotoxicity to 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.
Source: Bioconjugate Chemistry
DOI: 10.1021/bc200138d
Institutions: Lanzhou University, Hong Kong Polytechnic University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2011809273