Herein, we report the self-assembly and multimodal shape transformation of dual-responsive DNA di- and triblock copolymers. Dual-responsive DNA diblock copolymer was synthesized by coupling a thermoresponsive polymer, poly(N-isopropylacrylamide (PNIPAM), and an oligonucleotide. DNA-b-PNIPAM possesses thermoresponsive properties of PNIPAM as well as molecular recognition properties of DNA. Thus, they undergo reversible temperature-triggered transition at lower critical solution temperature (LCST) between molecular DNA and polymer micelles with high density DNA corona. The hybridization of DNA-b-PNIPAM and DNA-modified nanoparticles generates functional nanoparticles showing unique temperature-dependent aggregation and disaggregation behaviors due to the dual-responsive nature of DNA-b-PNIPAM. DNA triblock copolymers of DNA-b-PNIPAM-b-PMA were synthesized by introducing a hydrophobic block, poly(methyl acrylate) (PMA), to DNA/PNIPAM block copolymers, which form spherical micelles at room temperature. They are capable of nanoscale shape transformation through the combination of thermal trigger and DNA binding. DNA-b-PNIPAM-b-PMA micelles undergo sphere-to-cylinder shape changes above LCST due to the conformational change of PNIPAM. The shape change is reversible, and fast cylinder-to-sphere transition occurs when the temperature is lowered below LCST. The low temperature spherical morphology can also be accessed while keeping the temperature above LCST by introducing complementary DNA strands with single stranded overhang regions. These results demonstrate the multidimensional shape changing capability of DNA-b-PNIPAM-b-PMA enabled by the dual-responsive property.

Dynamic nanostructured materials that can react to physical and chemical stimuli have attracted interest in the biomedical and materials science fields. Metal–phenolic networks (MPNs) represent a modular class of such materials: these networks form via coordination of phenolic molecules with metal ions and can be used for surface and particle engineering. To broaden the range of accessible MPN properties, we report the fabrication of thermoresponsive MPN capsules using FeIII ions and the thermoresponsive phenolic building block biscatechol-functionalized poly­(N-isopropylacrylamide) (biscatechol-PNIPAM). The MPN capsules exhibited reversible changes in capsule size and shell thickness in response to temperature changes. The temperature-induced capsule size changes were influenced by the chain length of biscatechol-PNIPAM and catechol-to-FeIII ion molar ratio. The metal ion type also influenced the capsule size changes, allowing tuning of the MPN capsule mechanical properties. AlIII-based capsules, having a lower stiffness value (10.7 mN m–1), showed a larger temperature-induced size contraction (∼63%) than TbIII-based capsules, which exhibit a higher stiffness value (52.6 mN m–1) and minimal size reduction (<1%). The permeability of the MPN capsules was controlled by changing the temperature (25–50 °C)a reduced permeability was obtained as the temperature was increased above the lower critical solution temperature of biscatechol-PNIPAM. This temperature-dependent permeability behavior was exploited to encapsulate and release model cargo (500 kDa fluorescein isothiocyanate-tagged dextran) from the capsules; approximately 70% was released over 90 min at 25 °C. This approach provides a synthetic strategy for developing dynamic and thermoresponsive-tunable MPN systems for potential applications in biological science and biotechnology.

Cathepsin B has been suggested to be a prognostic marker of melanoma, glioma, and a variety of cancers such as brain, breast, colon, esophageal, gastric, lung, ovarian, and thyroid cancers. Cathepsin B inhibitors have also been considered as anticancer drug candidates; hence, there has been a growing need for a probe which enables the selective and simple detection of cathepsin B and its inhibitors. For the purpose of selective assay, a cathepsin B-specific substrate, N,N'-diBoc-dityrosine-glycine-phenylalanine-3-(methylthio)propylamine (DBDY-Gly-Phe-MTPA) was synthesized in this study. Phe-MTPA, which was produced via cathepsin B-catalyzed hydrolysis of DBDY-Gly-Phe-MTPA, allowed aggregation of gold nanoparticles (AuNPs) leading to a color change from red to blue. When tested for cathepsins B, L, and S, this assay method exhibited AuNPs color change only in reaction to cathepsin B. The limits of detection for cathepsin B was 10 and 5 nM in the 1 and 2 h hydrolysis reactions, respectively. The efficiency of cathepsin B inhibitors such as leupeptin, antipain, and chymostatin was easily compared by the degree of color change. Moreover, IC50 values of leupeptin, antipain, and chymostatin were found to be 0.11, 0.48, and 1.78 μM, respectively, which were similar to the results of previous studies. Therefore the colorimetric assay of cathepsin B and cathepsin B inhibitors using DBDY-Gly-Phe-MTPA and AuNPs allowed not only the selective but also the simple assay of cathepsin B and its inhibitors, which was possible with the naked eye.

Metal−phenolic networks (MPNs), formed through coordination bonding between phenolic molecules and metal ions, are a promising class of materials for engineering particle systems for diverse applications. However, the properties of such MPNs are inherently restricted due to the finite properties of naturally occurring phenolic molecules. Herein, we report a simple and robust approach to incorporate phenolic moieties into polymers, thereby providing customizable phenolic ligand building blocks that can be used to assemble capsules with a range of tailorable properties. The phenolic ligand building blocks were synthesized via carbonic anhydride coupling to terminal amines, a conjugation approach typically used for peptide coupling but applied herein for functionalizing polymers. The chemistry enabled optimized end-group purity, thus affording a robust and efficient strategy to generate a library of macromolecular poly(ethylene glycol) (PEG) catechol building blocks with different architectures (i.e., 2-, 4-, and 8-arm) and molecular weights (from 2.5 to 20 kDa). The resulting phenolic building blocks were applied to fabricate capsules with shell thickness, permeability, and cell association properties that were controlled via the variation of the macromolecular catechol architecture and molecular weight. Specifically, the shell thickness was varied more than 19fold (i.e., between ∼9 and 169 nm) by judicious selection of the polymer molecular weight, arm number, and template. Similarly, the permeability of the resulting MPN capsules to 500 kDa dextran was tuned from >90 to <5% by varying the number of arms in the polymer structure while maintaining a constant PEG M n -to-catechol group ratio. Furthermore, the cell association was reduced by a factor of 2.5 by employing 20 kDa 8-arm PEG instead of 2.5 kDa 2-arm PEG during film assembly. These results demonstrate that the applied macromolecular conjugation approach can be used to customize particle properties, potentially facilitating applications in therapeutic delivery, imaging, separations, and catalysis.

Binary self-assembly of DNA block copolymers and thermo-responsive block copolymers generated dynamic DNA nanostructures with unique capabilities to selectively block or unblock interactions with proteins and cells.