Category: Advanced materials and nanotechnology applications
Advances in the programmable self-assembly of
DNA hydrogel used for drug delivery
Gary Q. Yanga* Weibin Caib, Yujun Wangc
a
College of Bioscience and Bioengineering, Jiangxi Agricultural University, Nanchang,
Jiangxi, 330045, P. R. China.
b
School of Chemical and Environmental Engineering, China University of Mining and
Technology, Beijing 100083, P. R. China.
c
Department of Chemical Engineering, Tsinghua University, Beijing 100084, P. R. China.
*
*Corresponding author. Email: [email protected]
Abstract
Cancer is the deadliest disease for human beings and every year it may cause millions of deaths
globally. Traditional small-molecule drug administration often requires frequent administration
or high drug dosage to realize therapeutic efficacy due to nonspecific targeting. It often incurs
systemic adverse reaction, therefore lowering overall effects and patient compliance. The
emergence of immunotherapy and gene therapy, which involves functional biomolecules of
DNA, RNA and proteins, has presented new challenges for in vivo drug delivery. Naked
nucleic acids and proteins have short serum half-lives because of their susceptibility to
enzymatic degradation, and cell transfection efficiency is rather low. In addition, the biological
activity of protein can be readily damaged during carrier encapsulation. Therefore, it is
essential to develop active and effective carriers for the controllable delivery of small-molecule
and biomolecule drugs. Researchers have developed numerous targeted drug delivery systems
(DDSs) due to the rapid progress of drug vectors including nanoparticles, polymers and
liposomes, but these synthetic materials have poor degradability and low biocompatibility.
DNA hydrogels are comprised of hydrophilic polymeric networks of crosslinked DNA chains.
For their properties of good degradability and high biocompatibility in addition to porosity,
sequence programmability, tunable mechanical properties, controlled phase transformation and
simple preparation, extensive researches have been performed to construct DDS with DNA
hydrogels via programmable DNA-aid self-assembly for targeted drug release. To figure out
1
the advancement trend of the self-assembly techniques and keep pace with its recent rapid
advancements, it is essential to provide an overview of its past and recent progress. In the
review article, we first present the techniques researchers used to construct various hydrogels
made of solely DNA strands via programmable DNA-aided self-assembly. Then we present the
techniques that researchers used to assemble MFs with one or more additional type of
construction material, e.g., inorganic nanoparticle or polymers (including RNA, protein, etc.),
in addition to DNA strands for the purpose of endowing the DDS with improved or additional
properties/functions (e.g., designability, programmability, addressability, tunability and binding
ability, reversibility of assembly, transfection, multiple payload loading, drug-loading capacity,
cell internalization, biosafety, immunocompatibility, nuclease-resistant stability, stimuli-
responsibility, therapeutic efficacy, spatio-temporal controlled delivery, cancer dual/multiple
targeting, etc.). Here the additional construction materials may also classified into two
categories. The first one is purely used for construction purposes. The other one have
additional functions, e.g., tumor cell-targeting, stimuli-response, or themselves being drugs.
From the advancing trend of DNA hydrogel self-assembly nanotechniques, we anticipate that in
the future researchers will combine more materials with DNA strands to assemble more
complex and powerful DNA hydrogels and incorporate more functional components to endow
the DDS with improved or additional properties/functions, contributing to cancer prevention.