TY - JOUR
T1 - A library of aminoglycoside-derived lipopolymer nanoparticles for delivery of small molecules and nucleic acids
AU - Godeshala, Sudhakar
AU - Miryala, Bhavani
AU - Dutta, Subhadeep
AU - Christensen, Matthew D.
AU - Nandi, Purbasha
AU - Chiu, Po-Lin
AU - Rege, Kaushal
N1 - Funding Information:
We are grateful to the NIH/NIGMS (Grant 1R01GM093229-01A1), Arizona Biomedical Research Commission (ABRC; ADHS14-082981), and National Science Foundation (Grant 1836525) for funding this study. We are thankful to Professor Deirdre Meldrum, Center for Biosignatures Discovery Automation (CBDA), for access to the Zetasizer Nano-ZS instrument and to Dr Yanqing Tian, CBDA, for several helpful technical discussions. We also thank Dr Page Baluch at the Regenerative Medicine and Bioimaging facility at Arizona State University for her invaluable help with confocal microscopy. The authors also acknowledge resources and support from the Magnetic Resonance Research Center (MRRC); Eyring Materials Center; and the Metals, Environmental and Terrestrial Analytical Laboratory; which are part of the Core Facilities at Arizona State University.
PY - 2020/10/7
Y1 - 2020/10/7
N2 - Simultaneous delivery of small molecules and nucleic acids using a single vehicle can lead to novel combination treatments and multifunctional carriers for a variety of diseases. In this study, we report a novel library of aminoglycoside-derived lipopolymers nanoparticles (LPNs) for the simultaneous delivery of different molecular cargoes including nucleic acids and small-molecules. The LPN library was screened for transgene expression efficacy following delivery of plasmid DNA, and lead LPNs that showed high transgene expression efficacies were characterized using hydrodynamic size, zeta potential, 1H NMR and FT-IR spectroscopy, and transmission electron microscopy. LPNs demonstrated significantly higher efficacies for transgene expression than 25 kDa polyethyleneamine (PEI) and lipofectamine, including in presence of serum. Self-assembly of these cationic lipopolymers into nanoparticles also facilitated the delivery of small molecule drugs (e.g. doxorubicin) to cancer cells. LPNs were also employed for the simultaneous delivery of the small-molecule histone deacetylase (HDAC) inhibitor AR-42 together with plasmid DNA to cancer cells as a combination treatment approach for enhancing transgene expression. Taken together, our results indicate that aminoglycoside-derived LPNs are attractive vehicles for simultaneous delivery of imaging agents or chemotherapeutic drugs together with nucleic acids for different applications in medicine and biotechnology. This journal is
AB - Simultaneous delivery of small molecules and nucleic acids using a single vehicle can lead to novel combination treatments and multifunctional carriers for a variety of diseases. In this study, we report a novel library of aminoglycoside-derived lipopolymers nanoparticles (LPNs) for the simultaneous delivery of different molecular cargoes including nucleic acids and small-molecules. The LPN library was screened for transgene expression efficacy following delivery of plasmid DNA, and lead LPNs that showed high transgene expression efficacies were characterized using hydrodynamic size, zeta potential, 1H NMR and FT-IR spectroscopy, and transmission electron microscopy. LPNs demonstrated significantly higher efficacies for transgene expression than 25 kDa polyethyleneamine (PEI) and lipofectamine, including in presence of serum. Self-assembly of these cationic lipopolymers into nanoparticles also facilitated the delivery of small molecule drugs (e.g. doxorubicin) to cancer cells. LPNs were also employed for the simultaneous delivery of the small-molecule histone deacetylase (HDAC) inhibitor AR-42 together with plasmid DNA to cancer cells as a combination treatment approach for enhancing transgene expression. Taken together, our results indicate that aminoglycoside-derived LPNs are attractive vehicles for simultaneous delivery of imaging agents or chemotherapeutic drugs together with nucleic acids for different applications in medicine and biotechnology. This journal is
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U2 - 10.1039/d0tb00924e
DO - 10.1039/d0tb00924e
M3 - Article
C2 - 32830211
AN - SCOPUS:85092216704
VL - 8
SP - 8558
EP - 8572
JO - Journal of Materials Chemistry B
JF - Journal of Materials Chemistry B
SN - 2050-7518
IS - 37
ER -