Stimuli-responsive releasing of gold nanoparticles and liposomes from aptamer-functionalized hydrogels

Controlled release of therapeutic agents is important for improving drug efficacy and reducing toxicity. Recently, hydrogels have been used for controlled release applications. While the majority of the previous work focused on releasing the cargo in response to physical stimuli such as temperature, light, electric field, and pH, we aim to trigger cargo release in the presence of small metabolites. In our system a DNA aptamer that can bind to adenosine, AMP, and ATP was used as a linker to attach either DNA-functionalized gold nanoparticles or liposomes to DNA-functionalized hydrogels. In the presence of the metabolite, both the nanoparticle and liposome cargos were released. The effect of salt, temperature, target concentration, and drying has been systematically studied. Interestingly, we found that the gel can be completely dried while retaining the DNA linkages and adenosine induced release was still achieved after rehydration. Our work demonstrates that aptamers can be used to control the release of drugs and other materials attached to hydrogels.

[1]  Ahsan Munir,et al.  Au NPs-aptamer conjugates as a powerful competitive reagent for ultrasensitive detection of small molecules by surface plasmon resonance spectroscopy. , 2009, Talanta.

[2]  J. Szostak,et al.  In vitro selection of functional nucleic acids. , 1999, Annual review of biochemistry.

[3]  F. Simmel,et al.  Controlled trapping and release of quantum dots in a DNA-switchable hydrogel. , 2007, Small.

[4]  Chad A. Mirkin,et al.  One-Pot Colorimetric Differentiation of Polynucleotides with Single Base Imperfections Using Gold Nanoparticle Probes , 1998 .

[5]  M. Mrksich,et al.  Dynamic hydrogels: translating a protein conformational change into macroscopic motion. , 2007, Angewandte Chemie.

[6]  A. Hoffman,et al.  Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH , 1995, Nature.

[7]  Juewen Liu,et al.  Preparation of aptamer-linked gold nanoparticle purple aggregates for colorimetric sensing of analytes , 2006, Nature Protocols.

[8]  Soong Ho Um,et al.  Enzyme-catalysed assembly of DNA hydrogel , 2006, Nature materials.

[9]  J. Karp,et al.  Nanocarriers as an Emerging Platform for Cancer Therapy , 2022 .

[10]  Tao Zhang,et al.  Self‐Assembled DNA Hydrogels with Designable Thermal and Enzymatic Responsiveness , 2011, Advanced materials.

[11]  T. Miyata,et al.  Biomolecule-sensitive hydrogels. , 2002, Advanced drug delivery reviews.

[12]  Toyoichi Tanaka,et al.  Collapse of Gels in an Electric Field , 1982, Science.

[13]  Michael Famulok,et al.  Functional aptamers and aptazymes in biotechnology, diagnostics, and therapy. , 2007, Chemical reviews.

[14]  Wang Li,et al.  A sensitive, label free electrochemical aptasensor for ATP detection. , 2009, Talanta.

[15]  D. C. Lin,et al.  Inducing reversible stiffness changes in DNA-crosslinked gels , 2005 .

[16]  B D Ratner,et al.  Glucose-sensitive membranes containing glucose oxidase: activity, swelling, and permeability studies. , 1985, Journal of biomedical materials research.

[17]  J. Ubbink,et al.  Organization and mobility of water in amorphous and crystalline trehalose , 2006, Nature materials.

[18]  Yingfu Li,et al.  Structure-switching signaling aptamers: transducing molecular recognition into fluorescence signaling. , 2004, Chemistry.

[19]  Yong Wang,et al.  A hybrid particle–hydrogel composite for oligonucleotide-mediated pulsatile protein release , 2010 .

[20]  D. C. Lin,et al.  Mechanical properties of a reversible, DNA-crosslinked polyacrylamide hydrogel. , 2004, Journal of biomechanical engineering.

[21]  Yong Wang,et al.  Hydrogel functionalization with DNA aptamers for sustained PDGF-BB release. , 2010, Chemical communications.

[22]  W. Tan,et al.  Engineering target-responsive hydrogels based on aptamer-target interactions. , 2008, Journal of the American Chemical Society.

[23]  C. Tsitsilianis Responsive reversible hydrogels from associative “smart” macromolecules , 2010 .

[24]  Y. Osada,et al.  A polymer gel with electrically driven motility , 1992, Nature.

[25]  Xiaoling Zhang,et al.  An aptamer cross-linked hydrogel as a colorimetric platform for visual detection. , 2010, Angewandte Chemie.

[26]  J. Szostak,et al.  A DNA aptamer that binds adenosine and ATP. , 1995, Biochemistry.

[27]  Mizuo Maeda,et al.  DNA-responsive hydrogels that can shrink or swell. , 2005, Biomacromolecules.

[28]  Bernard Yurke,et al.  Use of DNA Nanodevices in Modulating the Mechanical Properties of Polyacrylamide Gels , 2005, DNA.

[29]  Joan W. Miller,et al.  Addendum to “Photosensitizer delivery for photodynamic therapy of choroidal neovascularization” , 2001 .

[30]  Juewen Liu,et al.  Electrostatically directed visual fluorescence response of DNA-functionalized monolithic hydrogels for highly sensitive Hg²+ detection. , 2011, ACS applied materials & interfaces.

[31]  Allan S Hoffman,et al.  Hydrogels for biomedical applications. , 2002, Advanced drug delivery reviews.

[32]  Yingfu Li,et al.  Nucleic acid aptamers and enzymes as sensors. , 2006, Current opinion in chemical biology.

[33]  Scott Banta,et al.  Protein engineering in the development of functional hydrogels. , 2010, Annual review of biomedical engineering.

[34]  Yingfu Li,et al.  Structure-switching signaling aptamers. , 2003, Journal of the American Chemical Society.

[35]  Brendan D. Smith,et al.  Regenerable DNA-functionalized hydrogels for ultrasensitive, instrument-free mercury(II) detection and removal in water. , 2010, Journal of the American Chemical Society.

[36]  Brendan D. Smith,et al.  DNA-functionalized monolithic hydrogels and gold nanoparticles for colorimetric DNA detection. , 2010, ACS applied materials & interfaces.

[37]  R. Langer,et al.  Designing materials for biology and medicine , 2004, Nature.

[38]  Itamar Willner,et al.  Integrated nanoparticle-biomolecule hybrid systems: synthesis, properties, and applications. , 2004, Angewandte Chemie.

[39]  Kinam Park,et al.  Environment-sensitive hydrogels for drug delivery , 2001 .

[40]  Zhi Zhu,et al.  Photoresponsive DNA-cross-linked hydrogels for controllable release and cancer therapy. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[41]  Juewen Liu,et al.  Functional nucleic acid sensors. , 2009, Chemical reviews.

[42]  Bryan Wei,et al.  Aptamer based reversible DNA induced hydrogel system for molecular recognition and separation. , 2010, Chemical communications.

[43]  Y. Osada,et al.  Polymer Gels and Networks , 2001 .

[44]  T. Matsuda,et al.  Hydrogel formation via hybridization of oligonucleotides derivatized in water-soluble vinyl polymers , 1996 .

[45]  Sarah J. Hurst,et al.  "Three-dimensional hybridization" with polyvalent DNA-gold nanoparticle conjugates. , 2008, Journal of the American Chemical Society.

[46]  Chunhai Fan,et al.  Target-responsive structural switching for nucleic acid-based sensors. , 2010, Accounts of chemical research.

[47]  Dongsheng Liu,et al.  A pH-triggered, fast-responding DNA hydrogel. , 2009, Angewandte Chemie.

[48]  Y. Bae,et al.  Thermosensitive sol-gel reversible hydrogels. , 2002, Advanced drug delivery reviews.

[49]  D. Mooney,et al.  Hydrogels for tissue engineering. , 2001, Chemical Reviews.

[50]  Toyoichi Tanaka Collapse of Gels and the Critical Endpoint , 1978 .

[51]  C. van Nostrum,et al.  Novel crosslinking methods to design hydrogels. , 2002, Advanced drug delivery reviews.

[52]  E. Gil,et al.  Stimuli-reponsive polymers and their bioconjugates , 2004 .

[53]  Juewen Liu,et al.  Programmable assembly of DNA-functionalized liposomes by DNA. , 2011, ACS nano.

[54]  S. Jayasena Aptamers: an emerging class of molecules that rival antibodies in diagnostics. , 1999, Clinical chemistry.