MicroRNA Delivery by Multifunctional Lipoplexes in Lung
Cancer Therapy and Imaging
Yun Wu1, Chang Liu1, Qixin Wang1, Joseph Spernyak2
1
Department of Biomedical Engineering, State University of New York at Buffalo, 332 Bonner
Hall, Buffalo, NY 14260, United States
2
Roswell Park Cancer Institute, Buffalo, NY 14263, United States
ABSTRACT
Lung cancer accounts for 30% of all cancer-related death worldwide and its five year mortality
has only decreased by 1.6 % since 1970s, reflecting the urgent need of more effective
therapies. Multifunctional nanoparticles that combine effective therapeutics, targeted delivery
and noninvasive imaging hold great potential in improving lung cancer survival rates.
MicroRNAs (miRNAs), a family of short endogenous noncoding RNAs, harbor critical functions
in the initiation and progression of lung cancer as tumor suppressors or oncogenes. Regulating
miRNA expression represents a potent, new class of anticancer therapy working through the
mechanism that affects multiple oncogenic pathways simultaneously, i.e. “one for all”. However,
microRNA-based therapeutics are faced with several challenges including limited serum
stability, poor cellular uptake and lack of tissue specificity.
Here, we report a transferrin receptor targeted lipoplexes (TfR-LP) containing microRNAs as the
therapeutics and gadolinium (Gd) as the contrast agent for magnetic resonance imaging (MRI).
MiR-29b, a tumor suppressor, was selected as the model therapeutics because it is significantly
down-regulated in lung tumors and closely related to lung cancer patient survival. The
therapeutic efficacy of TfR-LP-miR-29b-Gd was evaluated in A549 non-small cell lung cancer
cells and compared with siPORT™ NeoFX™ transfection agent (Life Technology Inc.).
Compared to NeoFX, TfR-LP delivered miR-29b in a more efficient manner with ~5 folds
increase in mature miR-29b expression in A549 cells. MiR-29b delivered by TfR-LP successfully
down-regulated the expression of 2 target genes, MCL-1 and CDK6, at both mRNA and protein
levels. Colony assay indicated that miR-29b delivered by TfR-LP significantly inhibited A549
tumorigenicity by ~34%, compared with ~21% by NeoFX. Overexpression of miR-29b increased
the sensitivity of A549 cells to chemotherapeutic agent, curcumin, by reducing the IC50 value of
curcumin by ~2 folds. TfR-LP treatment did not induce significant cytotoxicity in A549 cells. For
MRI capability, the longitudinal (T1) relaxivity of TfR-LP-miR-29b-Gd at 4.7 T and 37°C was 8.2
s-1 • mM-1, which was ~2.5 folds higher than commercial agent Magnevist® (Gd-DTPA, r1=3.1
s-1 • mM-1). Currently we are evaluating the therapeutic efficacy, imaging capability and
cytotoxicity of Tf-LP-miR-29b-Gd in vivo prior to clinical translation.
BIOGRAPHY
Dr. Yun Wu is an Assistant Professor in the Department of Biomedical Engineering at State
University of New York at Buffalo. She received her Ph.D. from the Department of Chemical and
Biomolecular Engineering at the Ohio State University in 2009. After completion of her degree,
she received her postdoc training in the NSF Nanoscale Science and Engineering Center at the
th
8 Annual NYS Biotechnology Symposium
- May 19 & 20, 2016 -
Ohio State University. Dr. Wu’s research interest focuses on the development of multifunctional
nanoparticles based nanomedicine and biosensor for cancer imaging, therapy and diagnosis.
She has published 3 book chapters and >30 peer-reviewed papers. She received Biomedical
Engineering Innovation and Career Development Award from Biomedical Engineering Society in
2013 and UUP Discretionary Lump-Sum Award in 2015.
th
8 Annual NYS Biotechnology Symposium
- May 19 & 20, 2016 -