Targeting of EGF-displayed protein nanoparticles with anticancer drugs.
The development of protein-based carriers for drug delivery has been well studied. We previously constructed a protein-based nanoparticle consisting of genetically engineered elastin-like polypeptides (ELPs) with a fused poly-aspartic acid tail (ELPD ). The size of the self-assembled ELPD nanoparticles was regulated by charged repulsion of the poly-aspartic acid chains. In the present study, epidermal growth factor (EGF) was genetically fused to the C-terminus of ELPD to impart an active targeting ability to the ELPD nanoparticles. We examined the nanoparticle formation with EGF as well as its targeting ability. ELPD with fused EGF was found to form nanoparticles that displayed multivalent EGFs on their surface. EGF-displayed nanoparticles loaded with the anti-cancer drug paclitaxel were internalized into cells overexpressing the EGF receptor, and induced cell death.
Department of Environmental Chemistry and Engineering, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8502, Japan.
Rie
R
Matsumoto
Rieko
R
Hara
Takashi
T
Andou
Masayasu
M
Mie
Eiry
E
Kobatake
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D066246:ErbB Receptors / Q000819:agonists; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors
drug delivery system; elastin-like polypeptide; epidermal growth factor; protein-based nanoparticle; targeting