Peptide-based glioma-targeted drug delivery vector gHoPe2.
Gliomas are therapeutically challenging cancers with poor patient prognosis. New drug delivery strategies are needed to achieve a more efficient chemotherapy-based approach against brain tumors. The current paper demonstrates development of a tumor-targeted delivery vector that is based on a cell-penetrating peptide pVEC and a novel glioma-targeting peptide sequence gHo. The unique tumor-homing peptide gHo was identified using in vitro phage display technology. The novel delivery vector, which we designated as gHoPe2, was constructed by a covalent conjugation of pVEC, gHo, and a cargo; the latter could be either a labeling moiety (such as a fluorescent marker) or a cytostatic entity. Using a fluorescent marker, we demonstrate efficient uptake of the vector in glioma cells and selective labeling of glioma xenograft tumors in a mouse model. This is the first time that we know where in vitro phage display has yielded an efficient, in vivo working vector. We also demonstrate antitumor efficacy of the delivery vector gHoPe2 using a well-characterized chemotherapeutic drug doxorubicin. Vectorized doxorubicin proved to be more efficient than the free drug in a mouse glioma xenograft model after systemic administration of the drugs. In conclusion, we have characterized a novel glioma-homing peptide gHo, demonstrated development of a new and potential glioma-targeted drug delivery vector gHoPe2, and demonstrated the general feasibility of the current approach for constructing cell-penetrating peptide-based targeted delivery systems.
Institute of Technology, University of Tartu, Estonia.
Elo
E
Eriste
Kaido
K
Kurrikoff
Julia
J
Suhorutšenko
Nikita
N
Oskolkov
Dana Maria
DM
Copolovici
Sarah
S
Jones
Pirjo
P
Laakkonen
John
J
Howl
Ülo
Ü
Langel
D000595:Amino Acid Sequence; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000235:genetics; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D057846:Cell-Penetrating Peptides