Targeted delivery of anti-cancer growth inhibitory peptides derived from human alpha-fetoprotein: review of an International Multi-Center Collaborative Study.
The alpha-fetoprotein derived growth inhibitory peptide (GIP) is a 34-amino acid peptide composed of three biologically active subfragments. GIP-34 and its three constituent segments have been synthesized, purified, and studied for biological activity. The GIP-34 and GIP-8 have been characterized as anticancer therapeutic peptides. An multicenter study was initiated to elucidate the means by which these peptide drugs could be targeted to tumor cells. The study first established which cancer types were specifically targeted by the GIP peptides in both in vitro and in vivo investigations. It was next demonstrated that radiolabeled peptide ((125)I GIP-34) is specifically localized to rodent breast tumors at 24 h post-injection. The radionuclide studies also provided evidence for a proposed cell surface receptor; this was confirmed in a further study using fluorescent-labeled GIP-nanobeads which localized at the plasma membrane of MCF-7 breast cancer cells. Finally, it was readily demonstrated that GIP conjugated to either fluorescein or doxorubicin (DOX) underwent tumor cell uptake; subsequently, DOX-GIP conjugates induced cytotoxic cell destruction indicating the utility of GIP segments as cancer therapeutic agents. Following a discussion of the preceding results, a candidate cell surface receptor family was proposed which correlated with previous published reports for a putative AFP/GIP receptor.
Mizejewski
G J
GJ
Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, New York 12201, USA. mizejew@wadsworth.org
Mirowski
M
M
Garnuszek
P
P
Maurin
M
M
Cohen
B D
BD
Poiesz
B J
BJ
Posypanova
G A
GA
Makarov
V A
VA
Severin
E S
ES
Severin
S E
SE
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006131:Growth Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015337:Multicenter Studies as Topic; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D010446:Peptide Fragments; D000509:alpha-Fetoproteins; C554084:growth inhibitory peptide-34, human