The Use of α-fetoprotein for the Delivery of Cytotoxic Payloads to Cancer Cells

Abstract

One approach to improving the activity of anticancer drugs is to bind them to the human α-fetoprotein (HAFP) that recognizes the tumor-associated cell-surface HAFP receptor. A drug can be bound to the HAFP by covalent conjugation or within a non-covalent complex. Specially designed linkers couple cytotoxins to the HAFP and ensure the stability of the HAFP-drug conjugate in the circulation and the activation of the drug in the cancer cell. On the other hand, AFP-drug non-covalent complexes can exploit the natural role of the AFP as a nutrition delivery "shuttle". In this article we review the design of HAFP-drug conjugates and AFP-drug complexes and their potential uses.

The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets

“…First, the AFP-CD receptor binding sites can constitute a homing device by which AFP conjugated to doxorubicin (DOX) can attach to tumor cell surface receptors [74,75]. The AFP-CD-DOX conjugate could potentially bind to SR identified sites on AFP-CD between AAs #480-530 in the present report.…”

Antimicrobial Peptides and Cancer: Potential Use of Antimicrobial-Like Peptides in Chemotherapy

“…The preceding discourse has presented the case that antimicrobial-like peptides could potentially be utilized as adjunct or single agents in the course of human cancer chemotherapy. It has also been previously established that the AFP molecule and its derived peptides could serve as carrier transport vehicles of chemo-drugs for delivery into cancer cells [31,50]. The biomedical literature is replete with reports that intact full-length AFP itself can bind chemodrugs and toxins in both a covalent and/or non-covalent manner [34,44,50].…”

Magic Bullet and Immunotherapy against Metastasis

“…Like cell membrane damage, organelle membrane damage cannot be repaired and leads to the whole cell death by apoptosis or auto digestion. So, the toxins that destroy organelle membranes do not rely on p53, and lead to inevitable cancer cell death are preferable for the magic bullet [6]. The only problem for organelles toxins is to be internalized specifically by cancer cells.…”

“…The only problem for organelles toxins is to be internalized specifically by cancer cells. Targeted delivery to cancer cells and organelle toxin internalization can be organized with different artificial nano-vehicles but we used natural AFP [6].…”

“…Receptor-positive embryo and cancer cells have definite benefits of targeted nutrient delivery ( Figure 1). That is why AFP loaded with the different toxins was used for the targeted chemotherapy [6,7]. The AFP receptor detection on the major immune suppressive cells -MDSC -was very promising [8,9].…”