Landscape phage fusion protein-mediated targeting of nanomedicines enhances their prostate tumor cell association and cytotoxic efficiency.
Tumor-specific cytotoxicity of drugs can be enhanced by targeting them to tumor receptors using tumor-specific ligands. Phage display offers a high-throughput approach to screen for the targeting ligands. We have successfully isolated phage fusion peptides selective and specific for PC3 prostate cancer cells. Also, we have demonstrated a novel approach of targeting liposomes through tumor-specific phage fusion coat proteins, exploiting the intrinsic properties of the phage coat protein as an integral membrane protein. Here we describe the production of Rhodamine-labeled liposomes as well as doxorubicin-loaded long-circulating liposomes targeted to PC3 prostate tumor cells via PC-specific phage peptides, as an extension of our previous studies. Targeting of labeled liposomes was demonstrated using fluorescence microscopy as well as flow cytometry. Targeting of doxorubicin-loaded liposomes enhanced their cytotoxic effect against PC3 cells in vitro, indicating a possible therapeutic advantage. The simplicity of the approach for generating targeted liposomes coupled with the ability to rapidly obtain tumor-specific phage fusion proteins via phage display may contribute to a combinatorial system for the production of targeted liposomal therapeutics for advanced stages of prostate tumor. From the clinical editor: This paper demonstrates targeting cytotoxic agents to tumor receptors using tumor-specific ligands. The authors describe the production of Rhodamine-labeled liposomes as well as doxorubicin loaded long circulating liposomes targeted to PC3 prostate tumor cells via PC-specific phage peptides. This approach may be especially relevant for advanced prostate tumors.
Department of Pathobiology, Auburn University, Auburn, Alabama 36849, USA.
Prashanth K
PK
Jayanna
Deepa
D
Bedi
James W
JW
Gillespie
Patricia
P
DeInnocentes
Tao
T
Wang
Vladimir P
VP
Torchilin
Richard C
RC
Bird
Valery A
VA
Petrenko
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D036022:Capsid Proteins / Q000737:chemistry*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D050997:Nanomedicine / Q000379:methods; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D021381:Protein Transport; D012235:Rhodamines / Q000737:chemistry
D000970:Antineoplastic Agents; D036022:Capsid Proteins; D008081:Liposomes; D019151:Peptide Library; D010455:Peptides; D012235:Rhodamines; D004317:Doxorubicin