Chlorotoxin bound magnetic nanovector tailored for cancer cell targeting, imaging, and siRNA delivery.
Ribonucleic acid interference (RNAi) is a powerful molecular tool that has potential to revolutionize the treatment of cancer. One major challenge of applying this technology for clinical application is the lack of site-specific carriers that can effectively deliver short interfering RNA (siRNA) to cancer cells. Here we report the development and assessment of a cancer-cell specific magnetic nanovector construct for efficient siRNA delivery and non-invasive monitoring through magnetic resonance imaging (MRI). The base of the nanovector construct is comprised of a superparamagnetic iron oxide nanoparticle core coated with polyethylene glycol (PEG)-grafted chitosan, and polyethylenimine (PEI). The construct was then further functionalized with siRNA and a tumor-targeting peptide, chlorotoxin (CTX), to improve tumor specificity and potency. Flow cytometry, quantitative RT-PCR, and fluorescence microscopy analyses confirmed receptor-mediated cellular internalization of nanovectors and enhanced gene knockdown through targeted siRNA delivery. The ability of this nanovector construct to generate specific contrast enhancement of glioblastoma cells was demonstrated through MR imaging. These findings suggest that this CTX enabled nanoparticle carrier may be well suited for delivery of RNAi therapeutics to brain cancer cells.
Veiseh
Omid
O
Department of Materials Science & Engineering, University of Washington, Seattle, WA 98195, USA.
Kievit
Forrest M
FM
Fang
Chen
C
Mu
Ni
N
Jana
Soumen
S
Leung
Matthew C
MC
Mok
Hyejung
H
Ellenbogen
Richard G
RG
Park
James O
JO
Zhang
Miqin
M
D000818:Animals; D045744:Cell Line, Tumor; D003102:Colloids; D003952:Diagnostic Imaging / Q000379:methods*; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D012604:Scorpion Venoms / Q000378:metabolism*
D003102:Colloids; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D012604:Scorpion Venoms; C091539:Chlorotoxin; D049452:Green Fluorescent Proteins