Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Physical Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Physical Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Biomaterials. 2014 Nov;35(33):9236-45. doi: 10.1016/j.biomaterials.2014.07.044. Epub 2014 Aug 10.
Collagens are over-expressed in various human cancers and subsequently degraded and denatured by proteolytic enzymes, thus making them a target for diagnostics and therapeutics. Genetically engineered bacteriophage (phage) is a promising candidate for the development of imaging or therapeutic materials for cancer collagen targeting due to its promising structural features. We genetically engineered M13 phages with two functional peptides, collagen mimetic peptide and streptavidin binding peptide, on their minor and major coat proteins, respectively. The resulting engineered phage functions as a therapeutic or imaging material to target degraded and denatured collagens in cancerous tissues. We demonstrated that the engineered phages are able to target and label abnormal collagens expressed on A549 human lung adenocarcinoma cells after the conjugation with streptavidin-linked fluorescent agents. Our engineered collagen binding phage could be a useful platform for abnormal collagen imaging and drug delivery in various collagen-related diseases.
胶原蛋白在各种人类癌症中过度表达,随后被蛋白酶降解和变性,因此成为诊断和治疗的靶点。由于其有前途的结构特征,基因工程噬菌体(噬菌体)是开发用于癌症胶原蛋白靶向的成像或治疗材料的有前途的候选物。我们分别在 M13 噬菌体的次要和主要衣壳蛋白上基因工程化了两种功能肽,即胶原蛋白模拟肽和链霉亲和素结合肽。所得的工程噬菌体可作为治疗或成像材料,靶向癌症组织中降解和变性的胶原蛋白。我们证明,在与链霉亲和素连接的荧光剂缀合后,工程噬菌体能够靶向和标记 A549 人肺腺癌细胞上表达的异常胶原蛋白。我们的工程胶原蛋白结合噬菌体可能成为各种与胶原蛋白相关疾病中异常胶原蛋白成像和药物递送的有用平台。