Application of Bld-1-Embedded Elastin-Like Polypeptides in Tumor Targeting

Abstract

Expression of various molecules on the surface of cancer cells compared to normal cells creates a platform for the generation of various drug vehicles for targeted therapy. Multiple interactions between ligands and their receptors mediated by targeting peptide-modified polymer could enable simultaneous delivery of a drug selectively to target tumor cells, thus limiting side effects resulting from non-specific drug delivery. In this study, we synthesized a novel tumor targeting system by using two key elements: (1) Bld-1 peptide (SNRDARRC), a recently reported bladder tumor targeting peptide identified by using a phage-displayed peptide library, and (2) ELP, a thermally responsive polypeptide. B5V60 containing five Bld-1 peptides and non-targeted ELP77 with a thermal phase-transition over 37 °C were analyzed to determine their bioactivities. Further studies confirmed the superior binding ability of B5V60 to bladder tumor cells and the cellular accumulation of B5V60 in cancer cells was dependent on the expression level of sialyl-Tn antigen (STn), a tumor-associated carbohydrate antigen. Additionally, B5V60 displayed excellent localization in bladder tumor xenograft mice after intravenous injection and was strictly confined to sialyl-Tn antigen-overexpressing tumor tissue. Thus, our newly designed B5V60 showed high potential as a novel carrier for STn-specific targeted cancer therapy or other therapeutic applications.

Biosynthesized Multivalent Lacritin Peptides Stimulate Exosome Production in Human Corneal Epithelium

“…The 23-mer LP was genetically fused to the N-terminus of an elastin-like polypeptide (ELP) termed A96 ( Table 1 ). Emerging as an attractive recombinant protein–polymer choice for diverse applications, ELPs are under exploration as a drug delivery platform since their biosynthesis produces pharmacologically relevant, monodisperse, biodegradable, and biocompatible entities [ 20 , 21 , 22 ]. The sequence confirmed cDNA encoding the LP-A96 fusion protein was subjected to heterologous expression via bacterial fermentation.…”

The Recent Advance of Cell-Penetrating and Tumor-Targeting Peptides as Drug Delivery Systems Based on Tumor Microenvironment

“…Their research showed that B 5 V 60 had good binding ability with bladder tumor cells and can accumulate in tumor cells. After intravenous injection of B 5 V 60 , it showed good localization in mice with bladder tumor transplantation tumors …”

Application of Elastin-like Polypeptide in Tumor Therapy

“…Despite the significant advantages and success achieved by introducing PEG and HSA in target proteins, a highly efficient, cost-effective and reliable precision genetically designed protein-polymer fusion complex with high yield, specificity, bioactivity and well sustained pharmacodynamics and pharmacokinetics is required. The emergence of ELPs as a classical binding module to facilitate the fusion and delivery of therapeutic molecules or provide a surface site for the attachment and display of PDs to increase pharmacokinetic properties has become the subject of intense research focus [ 50 , 51 ]. Thus, by using ELPs as a delivery module, target molecular drugs or peptide drugs can be encapsulated, attached or displayed on the surface of ELP nanoparticles.…”