TY - JOUR
T1 - DNA-Functionalized Metal-Organic Framework Nanoparticles for Intracellular Delivery of Proteins
AU - Wang, Shunzhi
AU - Chen, Yijing
AU - Wang, Shuya
AU - Li, Peng
AU - Mirkin, Chad A.
AU - Farha, Omar K.
N1 - Funding Information:
This material is based upon work supported by the following awards: Air Force Office of Scientific Research FA9550-14-1-0274, National Science Foundation’s MRSEC program (DMR-1121262) and made use of its Shared Facilities at the Materials Research Center of Northwestern University. O.K.F. gratefully acknowledge the Defense Threat Reduction Agency for financial support (HDTRA1-14-1-0014). Shunzhi.W. acknowledges support from the PPG Fellowship. Shuya.W. acknowledges support from the Ryan Fellowship at Northwestern University and the Chemistry of Life Processes (CLP) Predoctoral Training Program at Northwestern University.
Funding Information:
This material is based upon work supported by the following awards: Air Force Office of Scientific Research FA9550-14-1-0274 National Science Foundations MRSEC program (DMR-1121262) and made use of its Shared Facilities at the Materials Research Center of Northwestern University. O.K.F. gratefully acknowledge the Defense Threat Reduction Agency for financial support (HDTRA1-14-1-0014).
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/2/13
Y1 - 2019/2/13
N2 - Due to their large size, charged surfaces, and environmental sensitivity, proteins do not naturally cross cell-membranes in intact form and, therefore, are difficult to deliver for both diagnostic and therapeutic purposes. Based upon the observation that clustered oligonucleotides can naturally engage scavenger receptors that facilitate cellular transfection, nucleic acid-metal organic framework nanoparticle (MOF NP) conjugates have been designed and synthesized from NU-1000 and PCN-222/MOF-545, respectively, and phosphate-terminated oligonucleotides. They have been characterized structurally and with respect to their ability to enter mammalian cells. The MOFs act as protein hosts, and their densely functionalized, oligonucleotide-rich surfaces make them colloidally stable and ensure facile cellular entry. With insulin as a model protein, high loading and a 10-fold enhancement of cellular uptake (as compared to that of the native protein) were achieved. Importantly, this approach can be generalized to facilitate the delivery of a variety of proteins as biological probes or potential therapeutics.
AB - Due to their large size, charged surfaces, and environmental sensitivity, proteins do not naturally cross cell-membranes in intact form and, therefore, are difficult to deliver for both diagnostic and therapeutic purposes. Based upon the observation that clustered oligonucleotides can naturally engage scavenger receptors that facilitate cellular transfection, nucleic acid-metal organic framework nanoparticle (MOF NP) conjugates have been designed and synthesized from NU-1000 and PCN-222/MOF-545, respectively, and phosphate-terminated oligonucleotides. They have been characterized structurally and with respect to their ability to enter mammalian cells. The MOFs act as protein hosts, and their densely functionalized, oligonucleotide-rich surfaces make them colloidally stable and ensure facile cellular entry. With insulin as a model protein, high loading and a 10-fold enhancement of cellular uptake (as compared to that of the native protein) were achieved. Importantly, this approach can be generalized to facilitate the delivery of a variety of proteins as biological probes or potential therapeutics.
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U2 - 10.1021/jacs.8b12705
DO - 10.1021/jacs.8b12705
M3 - Article
C2 - 30669839
AN - SCOPUS:85061475862
VL - 141
SP - 2215
EP - 2219
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 6
ER -