A Novel Peptide Probe for Imaging and Targeted Delivery of Liposomal Doxorubicin to Lung Tumor

Abstract

Targeted delivery of imaging agents and therapeutics to tumors would provide early detection and increased therapeutic efficacy against cancer. Here we have screened a phage-displayed peptide library to identify peptides that selectively bind to lung tumor cells. Evaluation of individual phage clones after screening revealed that a phage clone displaying the CSNIDARAC peptide bound to H460 lung tumor cells at higher extent than other phage clones. The synthetic CSNIDARAC peptide strongly bound to H460 cells and was efficiently internalized into the cells, while little binding of a control peptide was seen. It also preferentially bound to other lung tumor cell lines as compared to cells of different tumor types. In vivo imaging of lung tumor was achieved by homing of fluorescence dye-labeled CSNIDARAC peptide to the tumor after intravenous injection into mice. Ex vivo imaging and microscopic analysis of isolated organs further demonstrated the targeting of CSNIDARAC peptide to tumor. The CSNIDARAC peptide-targeted and doxorubicin-loaded liposomes inhibited the tumor growth more efficiently than untargeted liposomes or free doxorubicin. In vivo imaging of fluorescence dye-labeled liposomes demonstrated selective homing of the CSNIDARAC-liposomes to tumor. In the same context, higher levels of doxorubicin and apoptosis in tumor tissue were observed when treated with the targeted liposomes than untargeted liposomes or free doxorubicin. These results suggest that the CSNIDARAC peptide is a promising targeting probe that is able to direct imaging agents and therapeutics to lung tumor.

Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging

“…Numerous studies have described methods for coating the surface of SPIONs and conjugating targeting ligands [11][12][13][14][15]. In this latter context, various affinity molecules, including antibodies, protein-scaffolds, aptamers and peptides, have been used to achieve cancer-specific targeting after conjugation to a variety of nanoparticles [16][17][18][19][20]. Peptide-based ligands have been of particular interest for such applications because functional groups can be easily introduced at the desired site to achieve site-specific conjugation, and their small size relative to antibodies or aptamers makes it possible to attain a high degree of conjugation [21][22][23][24].…”

Next-Generation Nanoantibacterial Tools Developed from Peptides

“…However, there are a few other examples of the use of distinct ferrite-based nanoparticles for biomedical applications [43][44][45] (all of them are iron oxide based but also contain another cation, for example, Co +2 or Mn +2 ). In particular, Scarberry et al [46] reported in vivo targeting and extraction of cancer cells by using Co-ferrite-based nanoparticles coated with YSA (Tyr-Ser-Ala) peptide, which binds to the RTK, specifically EphA2 receptors, which are overexpressed in ovarian and other cancer cells. This paper is interesting since it evaluates the possibility of removing metastatic cancer cells from the circulatory system through a magnetic separation (magnetophoresis), which might have an impact on the long-term survival rate of cancer patients.…”

Peptide-based targeting strategies for simultaneous imaging and therapy with nanovectors

“…Theranostic liposomal Dox was also studied by Lee and colleagues 47 for the imaging of doxorubicin at and the targeted delivery of doxorubicin to a lung tumor. Lung cancer is the leading cause of death due to cancer, and its high mortality rate appears to be derived from a low therapeutic index for chemotherapy and from late detection due to a lack of sensitive diagnostic biomarkers.…”