Single-chain polymer nanoparticles in controlled drug delivery and targeted imaging

As a relatively new class of materials, single-chain polymer nanoparticles (SCNPs) just entered the field of (biomedical) applications, with recent advances in polymer science enabling the formation of bio-inspired nanosized architectures. Exclusive intramolecular collapse of individual polymer chains results in individual nanoparticles. With sizes an order of magnitude smaller than conventional polymer nanoparticles, SCNPs are in the size regime of many proteins and viruses (1-20 nm). Multifaceted syntheses and design strategies give access to a wide set of highly modular SCNP materials. This review describes how SCNPs have been rendered water-soluble and highlights ongoing research efforts towards biocompatible SCNPs with tunable properties for controlled drug delivery, targeted imaging and protein mimicry

Dynamic Nuclear Polarization of Silicon Carbide Micro- and Nanoparticles

[Image: see text] Two dominant crystalline phases of silicon carbide (SiC): α-SiC and β-SiC, differing in size and chemical composition, were investigated regarding their potential for dynamic nuclear polarization (DNP). (29)Si nuclei in α-SiC micro- and nanoparticles with sizes ranging from 650 nm to 2.2 μm and minimal oxidation were successfully hyperpolarized without the use of free radicals, while β-SiC samples did not display appreciable degrees of polarization under the same polarization conditions. Long T(1) relaxation times in α-SiC of up to 1600 s (∼27 min) were recorded for the (29)Si nuclei after 1 h of polarization at a temperature of 4 K. Interestingly, these promising α-SiC particles allowed for direct hyperpolarization of both (29)Si and (13)C nuclei, resulting in comparably strong signal amplifications. Moreover, the T(1) relaxation time of (13)C nuclei in 750 nm-sized α-SiC particles was over 33 min, which far exceeds T(1) times of conventional (13)C DNP probes with values in the order of 1–2 min. The present work demonstrates the feasibility of DNP on SiC micro- and nanoparticles and highlights their potential as hyperpolarized magnetic resonance imaging agents

Pentafluorophenyl-based single-chain polymer nanoparticles as a versatile platform towards protein mimicry

Proteins are biopolymers folded into 3D-structures and are omnipresent in biological systems, where they fulfil a wide array of complex functions. Mimicking the exceptional characteristics of proteins with synthetic analogues may likewise give unprecedented control over a nanomaterial's pharmacokinetic behaviour, enabling controlled delivery of therapeutics or imaging agents. Recent advances in polymer science have enabled the formation of bio-inspired single-chain polymer nanoparticles (SCNPs), which are formed by intramolecular collapse of individual polymer chains, and display sizes ranging from 5-20 nm. Here, we describe the preparation of SCNPs containing activated ester moieties, facilitating SCNP functionalization without altering its backbone structure. Pentafluorophenyl-functional SCNPs were prepared through intramolecular thiol-Michael addition crosslinking of thiol-functional precursor copolymers. Post-formation functionalization of the resulting SCNPs through substitution of the activated pentafluorophenyl esters with a variety of amines resulted in a series of water-soluble SCNPs with fluorescent labels, 'click' functionality, amino acids and even peptides. This synthetic strategy offers a straightforward method towards SCNP modification and SCNP-protein hybrids, giving access to easily adjustable physicochemical properties and protein mimicry

Glucose Single-Chain Polymer Nanoparticles for Cellular Targeting

Naturally occurring glycoconjugates possess carbohydrate moieties that fulfill essential roles in many biological functions. Through conjugation of carbohydrates to therapeutics or imaging agents, naturally occurring glycoconjugates are mimicked and efficient targeting or increased cellular uptake of glycoconjugated macromolecules is achieved. In this work, linear and cyclic glucose moieties were functionalized with methacrylates via enzymatic synthesis and used as building blocks for intramolecular cross-linked single-chain glycopolymer nanoparticles (glyco-SCNPs). A set of water-soluble sub-10 nm-sized glyco-SCNPs was prepared by thiol-Michael addition cross-linking in water. Bioactivity of various glucose-conjugated glycopolymers and glyco-SCNPs was evaluated in binding studies with the glucose-specific lectin Concanavalin A and by comparing their cellular uptake efficiency in HeLa cells. Cytotoxicity studies did not reveal discernible cytotoxic effects, making these SCNPs promising candidates for ligand-based targeted imaging and drug delivery

Biocompatible Single-Chain Polymer Nanoparticles for Drug Delivery A Dual Approach

Single-chain polymer nanoparticles (SCNPs) are protein-inspired materials based on intramolecularly cross linked polymer chains. We report here the development of SCNPs as uniquely sized nanocarriers that are capable of drug encapsulation independent of the polarity of the employed medium. Synthetic routes are presented for SCNP preparation in both organic and aqueous environments. Importantly, the SCNPs in organic media were successfully rendered water soluble, resulting in two complementary pathways toward water-soluble SCNPs with comparable resultant physicochemical characteristics. The solvatochromic dye Nile red was successfully encapsulated inside the SCNPs following both pathways, enabling probing of the SCNP interior. Moreover, the antibiotic rifampicin was encapsulated in organic medium, the loaded nanocarriers were rendered water soluble, and a controlled release of rifampicin was evidenced. The absence of discernible cytotoxic effects and promising cellular uptake behavior bode well for the application of SCNPs in controlled therapeutics delivery

Dynamic Nuclear Polarization of Silicon Carbide Micro- and Nanoparticles

Two dominant crystalline phases of silicon carbide (SiC): alpha-SiC and beta-SiC, differing in size and chemical composition, were investigated regarding their potential for dynamic nuclear polarization (DNP). Si-29 nuclei in alpha-SiC micro- and nanoparticles with sizes ranging from 650 nm to 2.2 mu m and minimal oxidation were successfully hyperpolarized without the use of free radicals, while beta-SiC samples did not display appreciable degrees of polarization under the same polarization conditions. Long T-1 relaxation times in alpha-SiC of up to 1600 s (similar to 27 min) were recorded for the Si-29 nuclei after 1 h of polarization at a temperature of 4 K. Interestingly, these promising alpha-SiC particles allowed for direct hyperpolarization of both Si-29 and C-13 nuclei, resulting in comparably strong signal amplifications. Moreover, the T-1 relaxation time of C-13 nuclei in 750 nm-sized alpha-SiC particles was over 33 min, which far exceeds T-1 times of conventional C-13 DNP probes with values in the order of 1-2 min. The present work demonstrates the feasibility of DNP on SiC micro- and nanoparticles and highlights their potential as hyperpolarized magnetic resonance imaging agents.</p