TY - JOUR
T1 - Spherical Nucleic Acids with Tailored and Active Protein Coronae
AU - Zhang, Wuliang
AU - Meckes, Brian
AU - Mirkin, Chad A.
N1 - Funding Information:
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Awards U54CA199091 and R01CA208783. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. This work made use of the IMSERC MS Facility at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205), the State of Illinois, and the International Institute for Nanotechnology (IIN). This work was supported by the Northwestern University Flow Cytometry Core Facility supported by Cancer Center Support Grant NCI CA060553. B.M. acknowledges support from the Eden and Steven Romick Postdoctoral Fellowship through the American Committee for the Weizmann Institute of Science.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/12/26
Y1 - 2019/12/26
N2 - Spherical nucleic acids (SNAs) are nanomaterials typically consisting of a nanoparticle core and a functional, dense, and highly oriented oligonucleotide shell with unusual biological properties that make them appealing for many applications, including sequence-specific gene silencing, mRNA quantification, and immunostimulation. When placed in biological fluids, SNAs readily interact with serum proteins, leading to the formation of ill-defined protein coronae on the surface, which can influence the targeting capabilities of the conjugate. In this work, SNAs were designed and synthesized with functional proteins, such as antibodies and serum albumin, deliberately adsorbed onto their surfaces. These particles exhibit increased resistance to protease degradation compared with native SNAs but still remain functional, as they can engage in hybridization with complementary oligonucleotides. SNAs with adsorbed targeting antibodies exhibit improved cellular selectivity within mixed cell populations. Similarly, SNAs coated with the dysopsonizing protein serum albumin show reduced macrophage uptake, providing a strategy for tailoring selective SNA delivery. Importantly, the protein coronae remain stable on the SNAs in human serum, exhibiting a less than 45% loss of protein through exchange after 12 h at 37 °C. Taken together, these results show that protein-SNA complexes and the method used to prepare them provide a new avenue for enhancing SNA stability, targeting, and biodistribution.
AB - Spherical nucleic acids (SNAs) are nanomaterials typically consisting of a nanoparticle core and a functional, dense, and highly oriented oligonucleotide shell with unusual biological properties that make them appealing for many applications, including sequence-specific gene silencing, mRNA quantification, and immunostimulation. When placed in biological fluids, SNAs readily interact with serum proteins, leading to the formation of ill-defined protein coronae on the surface, which can influence the targeting capabilities of the conjugate. In this work, SNAs were designed and synthesized with functional proteins, such as antibodies and serum albumin, deliberately adsorbed onto their surfaces. These particles exhibit increased resistance to protease degradation compared with native SNAs but still remain functional, as they can engage in hybridization with complementary oligonucleotides. SNAs with adsorbed targeting antibodies exhibit improved cellular selectivity within mixed cell populations. Similarly, SNAs coated with the dysopsonizing protein serum albumin show reduced macrophage uptake, providing a strategy for tailoring selective SNA delivery. Importantly, the protein coronae remain stable on the SNAs in human serum, exhibiting a less than 45% loss of protein through exchange after 12 h at 37 °C. Taken together, these results show that protein-SNA complexes and the method used to prepare them provide a new avenue for enhancing SNA stability, targeting, and biodistribution.
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U2 - 10.1021/acscentsci.9b01105
DO - 10.1021/acscentsci.9b01105
M3 - Article
C2 - 31893228
AN - SCOPUS:85076809322
VL - 5
SP - 1983
EP - 1990
JO - ACS Central Science
JF - ACS Central Science
SN - 2374-7943
IS - 12
ER -