The synthesis of doxorubicin‐loaded metal–organic framework nanoparticles (NMOFs) coated with a stimuli‐responsive nucleic acid‐based polyacrylamide hydrogel is described. The formation of the hydrogel is stimulated by the crosslinking of two polyacrylamide chains, PA and PB, that are functionalized with two nucleic acid hairpins (4) and (5) using the strand‐induced hybridization chain reaction. The resulting duplex‐bridged polyacrylamide hydrogel includes the anti‐ATP (adenosine triphosphate) aptamer sequence in a caged configuration. The drug encapsulated in the NMOFs is locked by the hydrogel coating. In the presence of ATP that is overexpressed in cancer cells, the hydrogel coating is degraded via the formation of the ATP–aptamer complex, resulting in the release of doxorubicin drug. In addition to the introduction of a general means to synthesize drug‐loaded stimuli‐responsive nucleic acid‐based polyacrylamide hydrogel‐coated NMOFs hybrids, the functionalized NMOFs resolve significant limitations associated with the recently reported nucleic acid‐gated drug‐loaded NMOFs. The study reveals substantially higher loading of the drug in the hydrogel‐coated NMOFs as compared to the nucleic acid‐gated NMOFs and overcomes the nonspecific leakage of the drug observed with the nucleic‐acid‐protected NMOFs. The doxorubicin‐loaded, ATP‐responsive, hydrogel‐coated NMOFs reveal selective and effective cytotoxicity toward MDA‐MB‐231 breast cancer cells, as compared to normal MCF‐10A epithelial breast cells.
DNA-tethered poly-N-isopropylacrylamide copolymer chains, pNIPAM, that include nucleic acid tethers have been synthesized. They are capable of inducing pH-stimulated crosslinking of the chains by i-motif structures or to be bridged by Ag(+) ions to form duplexes. The solutions of pNIPAM chains undergo crosslinking at pH 5.2 or in the presence of Ag(+) ions to form hydrogels. The hydrogels reveal switchable hydrogel-to-solution transitions by the reversible crosslinking of the chains at pH 5.2 and the separation of the crosslinking units at pH 7.5, or by the Ag(+) ion-stimulated crosslinking of the chains and the reverse dissolution of the hydrogel by the cysteamine-induced elimination of the Ag(+) ions. The DNA-crosslinked hydrogels are thermosensitive and undergo reversible temperature-controlled hydrogel-to-solid transitions. The solid pNIPAM matrices are protected against the OH(-) or cysteamine-stimulated dissociation to the respective polymer solutions.
We present the assembly of asymmetric two-layer hybrid DNA-based hydrogels revealing stimuli-triggered reversibly modulated shape transitions. Asymmetric, linear hydrogels that include layer-selective switchable stimuli-responsive elements that control the hydrogel stiffness are designed. Trigger-induced stress in one of the layers results in the bending of the linear hybrid structure, thereby minimizing the elastic free energy of the systems. The removal of the stress by a counter-trigger restores the original linear bilayer hydrogel. The stiffness of the DNA hydrogel layers is controlled by thermal, pH (i-motif), K ion/crown ether (G-quadruplexes), chemical (pH-doped polyaniline), or biocatalytic (glucose oxidase/urease) triggers. A theoretical model relating the experimental bending radius of curvatures of the hydrogels with the Young's moduli and geometrical parameters of the hydrogels is provided. Promising applications of shape-regulated stimuli-responsive asymmetric hydrogels include their use as valves, actuators, sensors, and drug delivery devices.
Gold nanoparticles
(AuNPs) or gold nanorods (AuNRs) are loaded
in polyacrylamide hydrogels cooperatively cross-linked by bis-acrylamide
and nucleic acid duplexes or boronate ester–glucosamine and
nucleic acid duplexes. The thermoplasmonic properties of AuNPs and
AuNRs are used to control the stiffness of the hydrogels. The irradiation
of the AuNP-loaded (λ = 532 nm) or the AuNR-loaded (λ
= 808 nm) hydrogels leads to thermoplasmonic heating of the hydrogels,
the dehybridization of the DNA duplexes, and the formation of hydrogels
with lower stiffness. By ON/OFF irradiation, the hydrogels are switched
between low- and high-stiffness states. The reversible control over
the stiffness properties of the hydrogels is used to develop shape-memory
hydrogels and self-healing soft materials and to tailor thermoplasmonic
switchable drug release. In addition, by designing bilayer composites
of AuNP- and AuNR-loaded hydrogels, a reversible thermoplasmonic,
light-induced bending is demonstrated, where the bending direction
is controlled by the stress generated in the respective bilayer composite.
Stimuli-responsive polyacrylamide hydrogels crosslinked by glucosamine–boronate/G-quadruplexes or azobenzene-functionalized DNA reveal controlled stiffness using chemical or photochemical triggers.
Multi-triggered DNA/bipyridinium dithienylethene (DTE) hybrid carboxymethyl cellulose (CMC)-based hydrogels are introduced. DTE exhibits cyclic and reversible photoisomerization properties, switching between the closed state (DTE c ), the electron acceptor, and the open isomer (DTE o ) that lacks electron acceptor properties. One system introduces a dual stimuli-responsive hydrogel containing CMC chains modified with electron donor dopamine sites and self-complementary nucleic acids. In the presence of DTE c and the CMC scaffold, a stiff hydrogel is formed, cooperatively stabilized by dopamine/DTE c donor−acceptor interactions and by duplex nucleic acids. The cyclic and reversible formation and dissociation of the supramolecular donor−acceptor interactions, through light-induced photoisomerization of DTE, or via oxidation and subsequent reduction of the dopamine sites, leads to hydrogels of switchable stiffness. Another system introduces a stimuli-responsive hydrogel triggered by one of three alternative signals. The stiff, multi-triggered hydrogel consists of CMC chains cross-linked by dopamine/DTE c donor−acceptor interactions, and by supramolecular K + -stabilized G-quadruplexes. The G-quadruplexes are reversibly separated in the presence of 18-crown-6 ether and reformed upon the addition of K + . The stiff hydrogel undergoes reversible transitions between highstiffness and low-stiffness states triggered by light, redox agents, or K + /crown ether. The hybrid donor−acceptor/G-quadruplex cross-linked hydrogel shows shape-memory and self-healing features. By using three different triggers and two alternative memory-codes, e.g., the dopamine/DTE c or the K + -stabilized G-quadruplexes, the guided shape-memory function of the hydrogel matrices is demonstrated.
Photoresponsive hydrogels crosslinked by trans-azobenzene/β-cyclodextrin and duplex DNA or K+-G-quadruplex are described. The hydrogels reveal shape-memory functions and self-healing properties.
The covalent linkage of aptamer binding
sites to nanoparticle nanozymes
is introduced as a versatile method to improve the catalytic activity
of nanozymes by concentrating the reaction substrates at the catalytic
nanozyme core, thereby emulating the binding and catalytic active-site
functions of native enzymes. The concept is exemplified with the synthesis
of Cu
2+
ion-functionalized carbon dots (C-dots), modified
with the dopamine binding aptamer (DBA) or the tyrosinamide binding
aptamer (TBA), for the catalyzed oxidation of dopamine to aminochrome
by H
2
O
2
or the oxygenation of
l
-tyrosinamide
to the catechol product, which is subsequently oxidized to amidodopachrome,
in the presence of H
2
O
2
/ascorbate mixture. Sets
of structurally functionalized DBA-modified Cu
2+
ion-functionalized
C-dots or sets of structurally functionalized TBA-modified Cu
2+
ion-functionalized C-dots are introduced as nanozymes of
superior catalytic activities (aptananozymes) toward the oxidation
of dopamine or the oxygenation of
l
-tyrosinamide, respectively.
The aptananozymes reveal enhanced catalytic activities as compared
to the separated catalyst and respective aptamer constituents. The
catalytic functions of the aptananozymes are controlled by the structure
of the aptamer units linked to the Cu
2+
ion-functionalized
C-dots. In addition, the aptananozyme shows chiroselective catalytic
functions demonstrated by the chiroselective-catalyzed oxidation of
l
/
d
-DOPA to
l
/
d
-dopachrome. Binding
studies of the substrates to the different aptananozymes and mechanistic
studies associated with the catalytic transformations are discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.