DOI: 10.1002/asia.

201900574 Minireview

Multifunctional DNA Origami Nanoplatforms for Drug Delivery

Xuehe Lu,[a, b] Jianbing Liu,*[b] Xiaohui Wu,[b, c] and Baoquan Ding*[a, b, c]

Chem. Asian J. 2019, 14, 2193 – 2202 2193 T 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Abstract: DNA nanotechnology has been employed in the
construction of self-assembled nano-biomaterials with uni-
form size and shape for various biological applications, such
as bioimaging, diagnosis, or therapeutics. Herein, recent suc-
cessful efforts to utilize multifunctional DNA origami nano-
platforms as drug-delivery vehicles are reviewed. Diagnostic
and therapeutic strategies based on gold nanorods, chemo-
1. Introduction
DNA is not only genetic material, but also a representative
building block that employs classic Watson–Crick base pairing
for molecular self-assembly. The programmability of DNA nano-
structures and precise molecular recognition provide a tailored
strategy for the construction of functional DNA-based nano-
platforms. DNA nanotechnology, invented in the 1980s by the
group of Seeman, opened up a new research area.[1] In recent
years, much progress in biological applications of multifunc-
tional DNA nanoplatforms has been reported. DNA hydrogels
are employed in a variety of biological applications, such as
drug delivery,[2] sensing,[3] and 3D cell culture.[4] DNA tetrahedra
have been developed for drug delivery,[5] molecular diagnosis,[6]
and bioimaging.[7]
In particular, functional nanoplatforms based on the DNA or-
igami technique have attracted increasing interest in the fields
of bioimaging and cancer therapy. Rationally designed multi-
functional DNA origami nanoplatforms with structural pro-
grammability, spatial addressability, and excellent biocompati-
bility display several unique advantages for various biological
applications. The development of a DNA origami based drug-
delivery system is a gradual evolutionary process. There are
challenges and great opportunities to utilize multifunctional
DNA origami nanoplatforms for biomedical applications.
2. Evolution of DNA Origami Nanotechnology
In this section, we introduce the history of DNA origami nano-
technology and its rapid developments in recent years. Scale-
[a] X. Lu, Prof. B. Ding
School of Materials Science and Engineering
Zhengzhou University, Zhengzhou 450001 (P.R. China)http://www.bdinglab.-
com/
E-mail: dingbq@nanoctr.cn
[b] X. Lu, Dr. J. Liu, X. Wu, Prof. B. Ding
CAS Key Laboratory of Nanosystem and Hierarchical Fabrication
CAS Center for Excellence in Nanoscience
National Center for Nanoscience and Technology
11 BeiYiTiao, ZhongGuanCun, Beijing 100190 (P.R. China)
E-mail: liujb@nanoctr.cn
[c] X. Wu, Prof. B. Ding
University of Chinese Academy of Sciences
Beijing 100049 (P.R. China)
The ORCID identification number(s) for the author(s) of this article can be
found under:
https://doi.org/10.1002/asia.201900574.
Chem. Asian J. 2019, 14, 2193 – 2202 www.chemasianj.org
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therapeutic drugs, cytosine–phosphate–guanine, functional
proteins, gene drugs, and their combinations for optoacous-
tic imaging, photothermal therapy, chemotherapy, immuno-
logical therapy, gene therapy, and coagulation-based thera-
py are summarized. The challenges and opportunities for
DNA-based nanocarriers for biological applications are also
discussed.
up fabrication of DNA origami, RNA–DNA hybrid origami, 3D
DNA origami nanostructures, and some related computational
tools are described.
2.1. Self-Assembled DNA Origami Nanostructures
DNA origami represents a remarkable advance in the field of
DNA nanotechnology and molecular self-assembly. In 2006,
Rothemund first reported this fascinating technique and suc-
cessfully constructed a series of DNA origami nanostructures,
such as squares, triangles, disks, and five-pointed stars, in a
simple one-pot reaction (Figure 1).[8] This attractive technique
Figure 1. Examples of DNA origami nanostructures and the corresponding
AFM images. Reprinted from Ref. [8] with permission from Nature Publishing
Group, Copyright 2006.
employed a single-stranded DNA of 7249 bases as the “scaffold
strand” (obtained from the M13mp18 bacteriophage) and
about 200 chemically synthesized short oligonucleotides as
“staple strands” (complementary to different regions of the
scaffold) to construct desired DNA nanostructures with high
yield and reliable reproducibility. Since then, a wide variety of
2D DNA nanostructures have been reported by many groups
on the basis of the DNA origami technique. Subsequently,
nanoscale shapes of dolphins[9] and a Chinese map[10] were de-
signed and assembled by the groups of Kjems and He, respec-
tively.
DNA origami nanotechnology has compelling advantages
for the construction of different nanostructures with controlled
sizes and shapes. One important feature of DNA origami is ex-
cellent addressability on the surface of DNA origami. Function-
al ligands, biomolecules, and nanoscale objects can be precise-
ly organized on the desired position of DNA origami nano-
structures.
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2.2. Development of DNA Origami Nanotechnology
The DNA origami technique can potentially be used to con-
struct various functional nanostructures with customized sizes
and shapes. However, there is still a limitation to using this
strategy for nanoscale construction that originates from the
finite length of the standard DNA scaffold. This single-stranded
DNA scaffold limits the size and surface area of DNA origami.
Thus, large functional components cannot be accommodated
on regular DNA origami nanostructures. To overcome this
shortcoming, many strategies have been developed to fabri-
cate larger DNA nanostructures. For instance, Winfree et al. de-
veloped an algorithmic self-assembly from origami seeds for
programmable bottom-up fabrication (Figure 2 a).[11] Liu and
co-workers obtained larger and more complex nanostructures
through a linker-strand connection strategy (Figure 2 b).[12]
Qian and co-workers used multiple origami tiles to draw micro-
meter-scale DNA origami images, such as the Mona Lisa (Fig-
ure 2 c).[13] Sugiyama and co-workers used multiple origami
structures named 2D DNA jigsaw pieces to scale up origami
structures.[14] The group of Seeman developed DNA origami
arrays to scale up 2D DNA origami.[15] Liu and co-workers used
eight-helix bundles as staples to extend the sizes of DNA origa-
mi.[16] Based on long, single-stranded polymerase chain reac-
tion (PCR) amplification products, the group of Woolley suc-
cessfully obtained scaffold strands with different lengths.[17] In
research by Shin and co-workers, double-stranded (ds) DNA
could be employed as a scaffold to construct two discrete
nanoscale objects.[18] Li and co-workers prepared four long
single-stranded DNA with sequences of 10 563, 10 782, 21 261,
and 31 274 nucleotides to be used as scaffolds to construct
larger DNA origami nanostructures.[19]
In addition to the classical DNA-templated scaffold, RNA
transcripts can also be employed as RNA scaffolds to build
RNA–DNA hybrid origami. The group of Sugiyama successfully
fabricated seven-helix bundled rectangular structures and six-
helix bundled tubular structures by using RNA transcripts as
scaffolds and DNA sequences as staple strands.[20] The physical
properties of the assembled RNA–DNA hybrid origami can be
modified by the functionalized RNA scaffold. Moreover, various
functions based on the structure of RNA, such as RNA catalysis
and RNA interference (RNAi), can be introduced into the RNA–
DNA hybrid origami. Meanwhile, Mao and co-workers also con-
structed ribbon, rectangle, and triangle RNA–DNA hybrid origa-
mi structures, depending on the length of the RNA scaffolds.[21]
In addition to building 2D DNA nanostructures, various 3D
nanostructures can also be constructed through the DNA ori-
gami technique. For instance, Shih and co-workers presented
the first attempt to construct various 3D nanostructures, such
as monoliths, square nuts, a railed bridge, a genie’s bottle,
stacked crosses, and slotted crosses (Figure 2 d).[22] Gothelf and
co-workers successfully created an addressable 3D DNA box,
with a size of 42 V 36 V 36 nm3, which could be opened by pre-
designed DNA “keys” (Figure 2 e).[23] At the same time, Komiya-
na and Kuzuya constructed another box-shaped 3D DNA origa-
mi by selective closing of a preformed open motif.[24] Dietz and
co-workers constructed origami-based dynamic DNA nano-
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structures that could be reversibly reconfigured in three differ-
ent conformational states, depending on the indicated concen-
tration of cations in solution (Figure 2 f).[25] A closed DNA tetra-
hedral origami nanostructure was designed and fabricated by
Ke et al. (Figure 2 g).[26] Yan and co-workers constructed DNA
origami with complex 3D curvatures (Figure 2 h).[27] Hçgberg
Xuehe Lu received his BS degree (2015) from
Huaiyin Normal University and MS degree
(2018) from Shanghai University. He is cur-
rently a PhD candidate, working under the su-
pervision of Professor Baoquan Ding, at the
National Center for Nanoscience and Technol-
ogy and Zhengzhou University. His research
interests focus on the chemical modification
of DNA and biomedical applications.
Jianbing Liu received his PhD (2016) in chemi-
cal biology from Nankai University. Currently,
he is an assistant research professor at the
National Center for Nanoscience and Technol-
ogy. His research interests focus on the devel-
opment of delivery systems for gene therapy
based on DNA nanocarriers.
Xiaohui Wu received her BS degree from Tian-
jin University in 2018. She is currently an MS
candidate, working under the supervision of
Professor Baoquan Ding, at the National
Center for Nanoscience and Technology. Her
research interests focus on the self-assembly
of RNA–DNA hybrid origami for biological ap-
plications.
Baoquan Ding received his bachelor degree in
chemistry from Jilin University in 2000. He ob-
tained his PhD in 2006 from the Department
of Chemistry, New York University, under the
supervision of Professor Nadrian Seeman. He
then worked as a postdoctoral research fellow
at the Molecular Foundry, Lawrence Berkeley
National Laboratory. He joined the Biodesign
Institute, Arizona State University, as a re-
search assistant professor in October 2009. He
became a professor at the National Center for
Nanoscience and Technology, P.R. China, in
November 2010. His research interests include
DNA nanotechnology, coassembled biomole-
cules, and drug delivery.
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Figure 2. Some examples of self-assembled DNA nanostructures. a) 2D DNA origami by seeds. Reproduced from Ref. [11b] with permission from the National
Academy of Sciences, Copyright 2009. b) 2D DNA origami by linkers. Reproduced from Ref. [12] with permission from the American Chemical Society, Copy-
right 2010. c) 2D DNA origami by titles. Reproduced from Ref. [13] with permission from Nature Publishing Group, Copyright 2017. d) Multilayer 3D origami.
Reproduced from Ref. [22] with permission from Nature Publishing Group, Copyright 2009. e) Openable 3D DNA box. Reproduced from Ref. [23] with permis-
sion from Nature Publishing Group, Copyright 2009. f) 3D nanorobot origami. Reproduced from Ref. [25] with permission from the American Association for
the Advancement of Science, Copyright 2015. g) Closed DNA tetrahedral origami. Reproduced from Ref. [26] with permission from American Chemical Society,
Copyright 2009. h) 3D curvature. Reproduced from Ref. [27] with permission from the American Association for the Advancement of Science, Copyright 2011.
i) Wireframe DNA origami. Reproduced from Ref. [28] with permission from Nature Publishing Group, Copyright 2015.

and co-workers created wireframe DNA origami by means of
graph theory (Figure 2 i).[28] Thus, the construction of 3D DNA
nanostructures has dramatically increased the diversification of
DNA nanostructures.
Nowadays, several computational tools have been devel-
oped for the design of various DNA nanostructures, such as
SARSE-DNA,[29] caDNAno,[30] and CanDo.[31] Recently, software
with a fully automatic inverse design procedure, named DAE-
DALUS, was developed by Veneziano et al. to construct various
DNA nanostructures with tailored sizes and shapes.[32] This soft-
ware grants easy access to the DNA origami technique to re-
searchers from different backgrounds. Multifunctional DNA
nanostructures can be rationally designed with these software
tools for a wide variety of applications.
3. Biological Applications
In this section, DNA origami nanostructures as vehicles for the
delivery of gold nanorods (GNRs), chemotherapeutic drugs, cy-
tosine–phosphate–guanine (CpG), functional proteins, gene
drugs, and their combinations for optoacoustic imaging, pho-
tothermal therapy, chemotherapy, immunological therapy,
gene therapy, and coagulation-based therapy are described.
and scattering in the near-infrared (NIR) region can be em-
ployed as excellent candidates for optoacoustic imaging and
photothermal therapy.[33]
Recently, Ding and co-workers successfully developed a self-
assembled DNA origami–GNR complex for dual-functional
nanotheranostics by combining the features of GNRs and DNA
origami nanostructures (Figure 3 a).[34] Compared with bare
GNRs, DNA origami–GNR complexes achieved a significant en-
hancement of cellular uptake in human MCF7 breast cancer
cells. In particular, the triangular DNA origami–GNR complex
demonstrated optimal cellular accumulation. In contrast to
bare GNRs, the triangular DNA origami–GNR complex showed
enhanced photothermolysis against tumor cells in vitro and in
vivo.
After observing the efficient photothermal therapy effect
based on the DNA origami–GNR complex, Tian and co-workers
subsequently developed GNR-loaded triangular DNA origami
to function as an optoacoustic imaging agent.[35] GNR-loaded
DNA origami can act as an efficient contrast agent to achieve
enhanced imaging quality with a decreased dose. Photother-
mal treatment based on this DNA origami–GNR complex dem-
onstrated efficient inhibition of tumor growth in vivo (Fig-
ure 3 b).

3.1. Delivery of GNRs 3.2. Delivery of Small-Molecule Drugs

Noble-metal nanoparticles with attractive size-dependent Chemotherapeutic drugs, such as doxorubicin (Dox) and dau-
properties present great promise for electronic, optical, and norubicin, can efficiently inhibit the proliferation of tumor cells
biomedical applications. Specially, GNRs with strong absorbing by intercalating into DNA base pairs to block the replication

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Figure 3. Examples of DNA origami for GNR delivery in biological applications. a) GNR-loaded DNA origami for photothermal therapy. DO-GNR = DNA origa-
mi–GNR complex. Reproduced from Ref. [34] with permission from Wiley-VCH, Copyright 2015. b) GNR-loaded DNA origami for optoacoustic imaging and
photothermal therapy. PBS = phosphate-buffered saline, D-AuNR = gold nanorods with DNA nanostructures. Reproduced from Ref. [35] with permission from
Wiley-VCH, Copyright 2016.
and transcription of functional genes. However, similar to other
traditional anticancer drugs, these chemotherapeutic drugs
also have adverse side effects and poor selectivity during
tumor therapy.[36] Targeted delivery of these chemotherapeutic
drugs would achieve efficient inhibition of tumor growth and
avoid systemic toxicity.
Ding and co-workers demonstrated that DNA origami nano-
structures had tremendous potential to act as a biocompatible
carrier of Dox for cancer therapy (Figure 4 a).[37] Dox can be effi-
ciently loaded into the DNA duplex through intercalation with
base pairs. The Dox-loaded DNA origami nanoplatform demon-
strated prominent cytotoxicity to drug-resistant human breast
cancer cells and successfully circumvented drug resistance in
vitro. Ding and co-workers subsequently employed Dox-loaded
triangular DNA origami to inhibit tumor growth in vivo (Fig-
ure 4 b).[38] The origami-based drug-delivery system demon-
strated efficient antitumor efficacy in vivo without inducing
observable systemic toxicity.
Hçgberg and co-workers employed two DNA origami nano-
structures to load Dox for the treatment of three different
breast cancer cell lines (MDA-MB-231, MDA-MB-468, and MCF-
7; Figure 4 c).[39] Depending on different degrees of twisting of
the DNA origami, the drug release kinetics can be rationally
controlled. This drug-loaded DNA origami also showed high
degrees of internalization and efficient inhibition of prolifera-
tion of tumor cells in vitro. Castro and co-workers employed a
rodlike DNA origami nanostructure to deliver the widely used
chemotherapeutic drug daunorubicin in a leukemia model
(Figure 4 d).[40] This drug-loaded DNA nanocarrier also demon-
strated efficient circumvention of drug resistance mediated by
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efflux pumps in leukemia cells at clinically relevant drug con-
centrations.
3.3. Delivery of CpG
CpG oligodeoxynucleotides (ODNs) have strong immunostimu-
latory effects. The natural immune system can recognize exter-
nal CpG sequences and initiate immune responses.[41] Because
CpG-containing ODNs have exhibited great potential as immu-
nostimulatory agents, various delivery systems for CpG-con-
taining ODNs have been developed. Liedl and co-workers used
a tubular DNA origami to load unmethylated CpG sequences
through DNA hybridization (Figure 5).[42] This DNA origami,
containing 62 CpG-ODNs, triggered higher immunostimulation
than that of equal amounts of CpG motifs delivered by Lipo-
fectamine. The CpG-modified DNA origami can be recognized
by TLR9 and induces remarkable cytokine production.
3.4. Delivery of Functional Proteins
The delivery of therapeutic proteins to disease sites is an effec-
tive strategy to treat cancer or other diseases.[43] A suitable de-
livery system is essential to achieve therapeutic effects. A func-
tional DNA origami nanoplatform can also be designed to real-
ize efficient protein delivery.
Transferrin (Tf) plays a key role in the transportation and me-
tabolism of iron through receptor-mediated endocytosis.[44]
Moreover, Tf has been successfully employed to facilitate the
delivery of macromolecular payloads[45] and various DNA con-
structs[46] in target cells. Kjems and co-workers first equipped a
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Figure 4. Examples of DNA origami for small-molecule drug delivery in biomedical applications. a) DNA origami for Dox delivery in vitro. Reproduced from
Ref. [37] with permission from the American Chemical Society, Copyright 2012. b) DNA origami for Dox delivery in vivo. Reproduced from Ref. [38] with per-
mission from the American Chemical Society, Copyright 2014. c) DNA origami for Dox delivery in vitro. Reproduced from Ref. [39] with permission from the
American Chemical Society, Copyright 2012. d) DNA origami for daunorubicin delivery. Reproduced from Ref. [40] with permission from Wiley-VCH, Copyright
2016.

planar DNA origami with Tf ligand to increase cellular uptake
in a cancer cell line (Figure 6 a).[47] The Tf-modified DNA origami
nanostructure demonstrated efficient cellular uptake through
receptor-mediated endocytosis.
Douglas and co-workers constructed a hexagonal DNA ori-
gami barrel (about 40 nm) to transport molecular payloads,
such as antibodies, to target cells (Figure 6 b).[48] Antibody Fab’’
fragments can be loaded into the molecular barrel through
DNA hybridization. Once the barrels are opened through anti-
gen recognition, the loaded antibodies can bind to cell-surface
receptors to inhibit the proliferation of target tumor cells.
Thrombin is an important blood coagulation protease that
stops bleeding. Zhao and co-workers constructed a tubular
DNA nanorobot to load thrombin in its inner cavity (Fig-
ure 6 c).[49] This multifunctional DNA nanorobot can induce co-
agulation in tumor-associated vessels, leading to efficient
tumor tissue thrombosis and tumor necrosis in tumor-bearing
mouse models.

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Figure 5. DNA origami for CpG delivery. Reproduced from Ref. [42] with permission from the American Chemical Society, Copyright 2011.
RNase A can efficiently degrade RNA molecules inside cells
to induce high cytotoxicity. Ding and co-workers employed an
aptamer-modified rectangular DNA origami nanosheet to load
and deliver RNase A into target tumor cells in vitro (Fig-
ure 6 d).[50] The RNase A loaded DNA origami nanoplatform can
efficiently penetrate the cell membrane and induce high inhibi-
tion of proliferation of target tumor cells.
3.5. Codelivery of Multiple Therapeutic Components
Multidrug resistance (MDR) is a major obstacle in the clinical
treatment of cancer. Much higher doses and different combi-
nations of chemotherapeutic drugs have been administered to
achieve a considerable therapeutic effect. This widely em-
ployed treatment strategy may function at an earlier stage, but
results in much stronger MDR for patients in the long run.[51]
Permeability glycoprotein (P-gp) is a member of the trans-
membrane adenosine triphosphate (ATP)-binding cassette
transporter superfamily. P-gp is overexpressed in many drug-
resistant tumor cells and functions as an efflux pump for many
chemotherapeutic drugs. Ding and co-workers constructed a
multifunctional DNA origami nanoplatform through the combi-
nation of Dox and GNRs to downregulate the expression of P-
gp and circumvent drug resistance of multidrug-resistant MCF-
7 cells in vitro (Figure 7 a).[52] Aptamer-modified multifunctional
DNA origami nanoplatforms can achieve efficient cellular
uptake, as verified by means of fluorescent and two-photon lu-
minescence imaging. After NIR laser irradiation, P-gp expres-
sion was efficiently downregulated to achieve combined che-
motherapeutic and photothermal therapy.
P53, as an important tumor suppressor gene, plays a key
role in the inhibition of the proliferation of tumor cells. Ding
and co-workers fabricated a triangular DNA origami containing
a linear tumor therapeutic gene (p53) and a chemotherapeutic
drug (Dox) for combined therapy of multidrug-resistant tumors
(Figure 7 b).[53] The aptamer-modified kitelike DNA origami
nanoplatform demonstrated efficient gene-delivery efficacy
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and exhibited high inhibition of multidrug-resistant tumor
growth in vivo without apparent systemic toxicity.
RNAi is a tailored technology to knock down the expression
of MDR-related genes. Ding and co-workers employed the
DNA origami nanoplatform to load and deliver small hairpin
RNA (shRNA) transcription templates that targeted MDR-associ-
ated genes P-gp and Survivin (Figure 7 c).[54] The Dox and
shRNA transcription templates for coloading DNA origami with
aptamer modifications can efficiently enter target cells and
induce a remarkable antitumor effect. This multifunctional
DNA origami nanoplatform can achieve the synergistic inhibi-
tion of tumor growth against multidrug-resistant tumors in
vivo.
4. Summary and Outlook
In recent decades, various DNA nanostructures have been con-
structed and utilized for biomedical applications. Herein, we
summarized recent progress in employing multifunctional DNA
origami nanoplatforms as drug-delivery vehicles. DNA origami
with structural programmability, spatial addressability, and ex-
cellent biocompatibility is tailored to load a variety of function-
al components at desired sites. Diagnostic and therapeutic
strategies based on GNRs, chemotherapeutic drugs, CpG, func-
tional proteins, gene drugs, and their combinations for bio-
imaging and cancer therapy were highlighted.
Although various multifunctional DNA origami nanoplat-
forms have been successfully developed for drug delivery, chal-
lenges still remain for their further application in vivo. First, a
better understanding of the systemic pharmacokinetics, includ-
ing internal circulation, biodistribution, and metabolism of
DNA origami nanocarriers with different sizes and shapes, is
still needed.[55] Second, the endocytosis mechanism and intra-
cellular fate of different DNA origami nanocarriers should be
further investigated. Finally, the possible immune response in-
duced by exogenous DNA should also be taken into account
carefully.
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Figure 6. Examples of DNA origami for protein delivery. a) Tf-loaded DNA origami for enhanced cellular uptake. Reproduced from Ref. [47] with permission
from Wiley-VCH, Copyright 2016. b) DNA nanorobot for antibody fragment delivery. Reproduced from Ref. [48] with permission from the American Association
for the Advancement of Science. Copyright 2012. c) DNA origami nanorobot for thrombin delivery. Reproduced from Ref. [49] with permission from Nature
Publishing Group, Copyright 2018. d) DNA origami for ribonuclease A (RNase A) delivery. Reproduced from Ref. [50] with permission from American Chemical
Society, Copyright 2019.

Despite the abovementioned challenges, DNA origami with Acknowledgements

customized functions can serve as a promising candidate for
efficient drug delivery. We believe that further developments
in DNA origami nanotechnology will provide a more intelligent
nanoplatform for diagnosis and disease therapy.
This work was supported by the National Natural Science
Foundation of China (21573051, 21708004, 51761145044); the
Science Fund for Creative Research Groups of the National Nat-
ural Science Foundation of China (21721002); the National
Basic Research Program of China (2016YFA0201601,

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Figure 7. Examples of DNA origami for the codelivery of multiple therapeutic components. a) DNA origami for Dox and GNR codelivery. Reproduced from
Ref. [52] with permission from the Royal Society of Chemistry, Copyright 2017. b) DNA origami for Dox and p53 gene codelivery. Reproduced from Ref. [53]
with permission from the American Chemical Society, Copyright 2018. c) DNA origami for Dox and RNAi codelivery. Reproduced from Ref. [54] with permission
from Wiley-VCH, Copyright 2018.
2018YFA0208900); the Key Research Program of Frontier Scien-
ces, CAS (grant QYZDB-SSW-SLH029); the CAS Interdisciplinary
Innovation Team; and the K. C. Wong Education Foundation.
Conflict of interest
The authors declare no conflict of interest.
Keywords: biological activity · DNA · DNA origami · drug
delivery · nanotechnology
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