Rennert Robert, Neundorf Ines, Beck-Sickinger Annette G
Leipzig University, Leipzig, Germany.
Methods Mol Biol. 2009;535:389-403. doi: 10.1007/978-1-59745-557-2_22.
An efficient cellular drug delivery is a severe problem due to the charge, the hydrophilic character or the size of many therapeutic agents. High-drug doses, necessary to compensate the reduced bioavailability, often cause strong adverse effects. Synthetic drug delivery vectors will solve this problem, if limitations like low-cellular uptake efficiency or cytotoxicity can be overcome. Among these synthetic vectors, so-called cell-penetrating peptides (CPP) have proven their applicability as drug carriers. The ability to penetrate cellular membranes without the help of any receptor or transporter molecule was also found for derivatives of the native peptide hormone human calcitonin (hCT). We have shown that truncated hCT analogs with a branched peptide design and oligocationic side chain sequences - hCT(18-32)-k 7 and hCT(9-32)-2 br - are very interesting candidates as carrier peptides for drug delivery. Both peptides were found to efficiently shuttle covalently linked small molecules and non-covalently complexed DNA and RNA inside human embryonic kidney cells (HEK 293).
由于许多治疗剂的电荷、亲水性或大小，高效的细胞药物递送是一个严峻的问题。为补偿降低的生物利用度而必需的高药物剂量常常会引起强烈的副作用。如果能够克服诸如低细胞摄取效率或细胞毒性等限制，合成药物递送载体将解决这个问题。在这些合成载体中，所谓的细胞穿透肽（CPP）已证明其作为药物载体的适用性。在天然肽激素人降钙素（hCT）的衍生物中也发现了无需任何受体或转运分子帮助即可穿透细胞膜的能力。我们已经表明，具有分支肽设计和寡阳离子侧链序列的截短hCT类似物——hCT(18 - 32)-k7和hCT(9 - 32)-2br——是非常有吸引力的药物递送载体肽候选物。发现这两种肽都能有效地将共价连接的小分子以及非共价复合的DNA和RNA转运到人胚胎肾细胞（HEK 293）内。
