Peptide-conjugated nanoparticles for targeted imaging and therapy of prostate cancer
Journal
Biomaterials
Journal Volume
99
Pages
1-15
Date Issued
2016
Author(s)
Abstract
While there has been extensive development of anti-cancer drugs for treatment of prostate cancer, the therapeutic efficacy of such drugs remains inadequate in many cases. Here, we performed in vitro biopanning of the PC3 human prostate carcinoma cell line to select prostate cancer-specific peptides by phage display. We successfully identified specific peptides targeting prostate cancer cells, and their specificity was confirmed by cellular ELISA and flow cytometry. Moreover, we found that the phage clones also recognize other prostate cancer cell lines and surgical specimens from prostate cancer patients. The tumor targeting ability of these phages was validated in a xenograft model, in which high accumulation of targeting phage was observed. To investigate whether selected peptides are able to target tumors and enhance drug delivery into cancer cells, we synthesized peptide-PEGylated lipids and post-inserted them into preformed liposomal doxorubicin and vinorelbine. The results of our cellular uptake and MTT assays indicate that peptide-conjugated liposomes exhibit enhanced drug intracellular delivery and cytotoxicity. The conjugation of targeting peptide to imaging agents, such as quantum dots (QDs) and superparamagnetic iron oxide nanoparticles (SPIONs), results in more precise delivery of these agents to tumor sites. Furthermore, administration of liposomal doxorubicin and vinorelbine conjugated with targeting peptides was found to markedly increase the inhibition of human prostate tumor growth in mouse xenograft and orthotopic models. These results indicate that targeting peptide, SP204, has significant potential for targeted therapy and molecular imaging in prostate cancer. ? 2016 Elsevier Ltd.
Subjects
Drug delivery systems; Molecular imaging; Peptide-conjugated nanoparticles; Phage display; Prostate cancer
SDGs
Other Subjects
Biological materials; Cell culture; Cells; Clone cells; Cytology; Enzyme inhibition; Liposomes; Molecular imaging; Nanoparticles; Peptides; Semiconductor quantum dots; Tumors; Urology; Conjugated liposomes; Drug delivery system; Intracellular delivery; Liposomal doxorubicin; Phage display; Prostate cancer cells; Prostate cancers; Superparamagnetic iron oxide nanoparticles; Diseases; antineoplastic agent; contrast medium; docetaxel; doxorubicin; liposome; macrogol; nanoparticle; navelbine; peptide; peptide conjugated nanoparticle; peptide PC204; peptide SP204 conjugated liposomal doxorubicin; peptide SP204 conjugated liposomal vinorelbine; peptide SP204 conjugated quantum dot; peptide SP204 conjugated superparamagnetic iron oxide nanoparticle; quantum dot; superparamagnetic iron oxide nanoparticle; unclassified drug; antineoplastic agent; contrast medium; doxorubicin; ferric ion; ferric oxide; macrogol derivative; metal nanoparticle; peptide; vinblastine; vinorelbine tartrate; animal experiment; animal model; animal tissue; antineoplastic activity; Article; binding affinity; bioluminescence; biopanning; cancer inhibition; cancer therapy; cell proliferation assay; controlled study; drug conjugation; drug cytotoxicity; drug delivery system; drug distribution; drug effect; drug efficacy; drug formulation; drug specificity; drug tumor level; enzyme linked immunosorbent assay; flow cytometry; human; human cell; human tissue; immunohistochemistry; in vitro study; median survival time; molecular imaging; mouse; MTT assay; nonhuman; nuclear magnetic resonance imaging; overall survival; phage display; priority journal; prostate cancer; prostate cancer cell line; tumor xenograft; analogs and derivatives; animal; cancer transplantation; cell survival; chemistry; diagnostic imaging; drug effects; HEK293 cell line; male; particle size; peptide library; prostate tumor; SCID mouse; surface property; tissue distribution; tumor cell line; Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Contrast Media; Doxorubicin; Drug Delivery Systems; Ferric Compounds; HEK293 Cells; Humans; Liposomes; Male; Metal Nanoparticles; Mice, SCID; Neoplasm Transplantation; Particle Size; Peptide Library; Peptides; Polyethylene Glycols; Prostatic Neoplasms; Surface Properties; Tissue Distribution; Vinblastine
Publisher
Elsevier Ltd
Type
journal article