DNA–Polymer Conjugates by Photoinduced RAFT Polymerization

Abstract

Conventional grafting-to approaches to DNA-polymer conjugates are often limited by low reaction yields due to the sterically hindered coupling of a pre-synthesized polymer to DNA. The grafting-from strategy, in contrast, allows to directly graft polymers from an initiator that is covalently attached to DNA. Herein, we report blue light-mediated reversible additionfragmentation chain-transfer (Photo-RAFT) polymerization from two different RAFT agentterminated DNA sequences using Eosin Y as the photocatalyst in combination with ascorbic acid. Three monomer families (methacrylates, acrylates and acrylamides) were successfully Max Planck Institute for Polymer Research-Author's Manuscript 2 polymerized from DNA employing Photo-RAFT polymerization. We demonstrate that the length of the grown polymer chain can be varied by altering the monomer to DNA-initiator ratio, while the self-assembly features of the DNA strands were maintained. In summary, we describe a convenient, light-mediated approach towards DNA-polymer conjugates via the grafting-from approach. Introduction The combination of synthetic polymers with the unique specificity and recognition properties of DNA gave rise to an all-new class of DNA-polymer hybrid materials. 1-5 In recent years, DNApolymer conjugates have emerged as versatile building blocks that provided enhanced stability to complex DNA nanostructures 6,7 or facilitated, e.g., the precise organization of polymeric structures by DNA. 8-12 In particular, the combination of DNA with a hydrophobic polymer chain resulted in amphiphilic species that formed supramolecular architectures such as micelles or vehicles. 13-15 These assemblies were intensively investigated in the context of drug delivery, 16-19 as scaffolds for directing organic reactions 20 or as virus-like particles. 21 Inspired by recent advances in designing more sophisticated 2D and 3D DNA architectures equipped with various functionalities, 22,23 polymer chains were organized within complex DNA scaffolds or grown from DNA origami templates in distinct nanostructures. 24,25 Until recently, grafting-to strategies of pre-synthesized polymers to DNA sequences were mainly accomplished following solid phase synthesis 13,20,26,27 or bioconjugation strategies, such as copper-mediated azide-alkyne, 28,29 thiol-ene, 30-32 amide 33-35 or recently also tetrazine-norbornene coupling. 36 While the major advantage related to both approaches is that the polymer can be thoroughly characterized prior to the coupling reaction, the nature of the polymer has to be Max Planck Institute for Polymer Research-Author's Manuscript 3 carefully selected, e. g., it must remain stable under the strongly basic conditions of DNA-cleavage from the solid support. Critically, variation of polymer lengths to, i.e., improve stability and bioactivity is more tedious via the grafting-to strategy and low reaction yields were reported. 32,37 Most likely, steric hindrance of the pre-formed polymer chain or the necessity to use organic solvents during the conjugation step caused ...

A Fluorescent Sensor Based on Reversible Addition-Fragmentation Chain Transfer Polymerization for the Early Diagnosis of Non-small Cell Lung Cancer

“…26,27 Kong and co-workers have proposed various kinds of electrochemical sensor based on RAFT polymerization or ATRP polymerization for detection of sequence-specific DNAs and suggested that RAFT has better bio-compatibility as transition-metal, Cu 2+ of ATRP can cause toxicity. 28,29 Because RAFT polymerization is harmless to biomolecules 30 , it has great application prospects as a simple and effective signal amplification technique for biosensing for biomolecule detection. However, fluorescence detection DNA based on RAFT polymerization signal amplification has not been reported yet.…”

DNA–Polymer Nanostructures by RAFT Polymerization and Polymerization‐Induced Self‐Assembly

“…In this respect, while the first solution-based RAFT polymerization from DNA was successful, it had to still rely on conventional degassing, which limited its robustness. [20] Thus, we applied enzyme degassing as a significant progress for transferring polymerization processes to ultralow volumes and low radical concentrations. [21,22] In this way, the access to DNA-diblock copolymers of the type DNA-A-B (A and B denote different synthetic polymer units), as well as random DNA copolymers was made possible (Figure 1).…”

Effective Utilization of NIR Wavelengths for Photo‐Controlled Polymerization: Penetration Through Thick Barriers and Parallel Solar Syntheses

“…[4] Echoing these developments,awide range of controlled photopolymerizations regulated by visible wavelengths have been developed, [5] creating new opportunities in the preparation of functional materials. [6] Although visible-and UVlight-mediated polymerizations are now well established, [7] there have been very few examples utilizing far-red or near infra-red (NIR) light due to their lower energy. [8] The enhanced penetration of non-transparent materials by these wavelengths are promising for the development of new and exciting applications.…”