Supramolecular polymer materials for biomedical applications and diagnostics

Self-assembly is an abundant process in nature and is vital to many processes in living organisms. During the last decade the fields of supramolecular chemistry and polymer science have made an integrated effort in the design, synthesis and application of supramolecular polymers. Supramolecular polymers rely on relatively weak non-covalent interactions such as hydrogen bonding, solvophobicity and π-stacking to self-assemble using a wide array of natural and artificially designed interaction motifs. Using these principles, both end-functionalized polymers interacting via molecular recognition and stacked monomers self-assembling into one-dimensional structures have been demonstrated. A uniquely naturally-occurring supramolecular polymer is DNA which, apart from its role in genetics, can be used as a building block for both structural and dynamic applications such as making well-organized three-dimensional lattices or reconfigurable and autonomously operating DNA-based devices. As every class of materials has their own advantages, designing multicomponent materials from multiple types of building blocks such as DNA, and supramolecular and covalent polymers, has the potential to create highly advanced, organized and responsive materials both from structural and functional points of view. This dissertation has focused on designing such multicomponent functional supramolecular materials for biomedical applications and diagnostics. Supramolecular & Biomaterials Chemistr

One-pot synthesis of defined-length ssDNA for multiscaffold DNA origami

DNA origami nanostructures generally require a single scaffold strand of specific length, combined with many small staple strands. Ideally, the length of the scaffold strand should be dictated by the size of the designed nanostructure. However, synthesizing arbitrary-length single-stranded DNA in sufficient quantities is difficult. Here, we describe a straightforward and accessible method to produce defined-length ssDNA scaffolds using PCR and subsequent selective enzymatic digestion with T7 exonuclease. This approach produced ssDNA with higher yields than other methods and without the need for purification, which significantly decreased the time from PCR to obtaining pure DNA origami. Furthermore, this enabled us to perform true one-pot synthesis of defined-size DNA origami nanostructures. Additionally, we show that multiple smaller ssDNA scaffolds can efficiently substitute longer scaffolds in the formation of DNA origami.Microscopic imaging and technolog

Reversible Loading of Nanoscale Elements on a Multicomponent Supramolecular Polymer System by Using DNA Strand Displacement

Supramolecular & Biomaterials Chemistr

Switching the mode of drug release from a reaction-coupled low-molecular-weight gelator system by altering its reaction pathway

Low-molecular-weight hydrogels are attractive scaffolds for drug delivery applications because of their modular and facile preparation starting from inexpensive molecular components. The molecular design of the hydrogelator results in a commitment to a particular release strategy, where either noncovalent or covalent bonding of the drug molecule dictates its rate and mechanism. Herein, we demonstrate an alternative approach using a reaction-coupled gelator to tune drug release in a facile and user-defined manner by altering the reaction pathway of the low-molecular-weight gelator (LMWG) and drug components through an acylhydrazone-bond-forming reaction. We show that an off-the-shelf drug with a reactive handle, doxorubicin, can be covalently bound to the gelator through its ketone moiety when the addition of the aldehyde component is delayed from 0 to 24 h, or noncovalently bound with its addition at 0 h. We also examine the use of an L-histidine methyl ester catalyst to prepare the drugloaded hydrogels under physiological conditions. Fitting of the drug release profiles with the Korsmeyer-Peppas model corroborates a switch in the mode of release consistent with the reaction pathway taken: increased covalent ligation drives a transition from a Fickian to a semi-Fickian mode in the second stage of release with a decreased rate. Sustained release of doxorubicin from the reaction-coupled hydrogel is further confirmed in an MTT toxicity assay with MCF-7 breast cancer cells. We demonstrate the modularity and ease of the reaction-coupled approach to prepare drug-loaded self-assembled hydrogels in situ with tunable mechanics and drug release profiles that may find eventual applications in macroscale drug delivery.Supramolecular & Biomaterials Chemistr

Grafting from a hybrid DNA-covalent polymer by hybridization chain reaction

Biological and Soft Matter Physic

Supramolecular polymer materials for biomedical applications and diagnostics

Self-assembly is an abundant process in nature and is vital to many processes in living organisms. During the last decade the fields of supramolecular chemistry and polymer science have made an integrated effort in the design, synthesis and application of supramolecular polymers. Supramolecular polymers rely on relatively weak non-covalent interactions such as hydrogen bonding, solvophobicity and π-stacking to self-assemble using a wide array of natural and artificially designed interaction motifs. Using these principles, both end-functionalized polymers interacting via molecular recognition and stacked monomers self-assembling into one-dimensional structures have been demonstrated. A uniquely naturally-occurring supramolecular polymer is DNA which, apart from its role in genetics, can be used as a building block for both structural and dynamic applications such as making well-organized three-dimensional lattices or reconfigurable and autonomously operating DNA-based devices. As every class of materials has their own advantages, designing multicomponent materials from multiple types of building blocks such as DNA, and supramolecular and covalent polymers, has the potential to create highly advanced, organized and responsive materials both from structural and functional points of view. This dissertation has focused on designing such multicomponent functional supramolecular materials for biomedical applications and diagnostics. </div

Dual-Crosslinked Human Serum Albumin Polymer Hydrogels for Affinity-Based Drug Delivery

Supramolecular & Biomaterials Chemistr

Switching the mode of drug release from a reaction-coupled low-molecular-weight gelator system by altering its reaction pathway

Low-molecular-weight hydrogels are attractive scaffolds for drug delivery applications because of their modular and facile preparation starting from inexpensive molecular components. The molecular design of the hydrogelator results in a commitment to a particular release strategy, where either noncovalent or covalent bonding of the drug molecule dictates its rate and mechanism. Herein, we demonstrate an alternative approach using a reaction-coupled gelator to tune drug release in a facile and user-defined manner by altering the reaction pathway of the low-molecular-weight gelator (LMWG) and drug components through an acylhydrazone-bond-forming reaction. We show that an off-the-shelf drug with a reactive handle, doxorubicin, can be covalently bound to the gelator through its ketone moiety when the addition of the aldehyde component is delayed from 0 to 24 h, or noncovalently bound with its addition at 0 h. We also examine the use of an L-histidine methyl ester catalyst to prepare the drugloaded hydrogels under physiological conditions. Fitting of the drug release profiles with the Korsmeyer-Peppas model corroborates a switch in the mode of release consistent with the reaction pathway taken: increased covalent ligation drives a transition from a Fickian to a semi-Fickian mode in the second stage of release with a decreased rate. Sustained release of doxorubicin from the reaction-coupled hydrogel is further confirmed in an MTT toxicity assay with MCF-7 breast cancer cells. We demonstrate the modularity and ease of the reaction-coupled approach to prepare drug-loaded self-assembled hydrogels in situ with tunable mechanics and drug release profiles that may find eventual applications in macroscale drug delivery

Crosslinker-Induced Effects on the Gelation Pathway of a Low Molecular Weight Hydrogel

Supramolecular & Biomaterials Chemistr