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

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

Measurement of the B0^0 and B+^+ meson lifetimes with fully reconstructed hadronic final states

The B0 and B+ meson lifetimes have been measured in e+e- annihilation data collected in 1999 and 2000 with the BABAR detector at center-of-mass energies near the Upsilon(4S) resonance. Events are selected in which one B meson is fully reconstructed in a hadronic final state while the second B meson is reconstructed inclusively. A combined fit to the B0 and the B+ decay time difference distributions yields tau_{B0} = 1.546 +/- 0.032 (stat) +/- 0.022(syst) ps, tau_{B+} = 1.673 +/- 0.032 (stat) +/- 0.023 (syst) ps and tau_{B+} / tau_{B0} = 1.082 +/- 0.026 (stat) +/- 0.012 (syst

Well-defined single-chain polymer nanoparticles via thiol-Michael addition

A synthetic strategy has been developed giving facile access to well-defined single-chain polymer nanoparticles (SCNPs) from styrene-, acrylate- and methacrylate-based polymers. Random copolymers (polydispersity indices 1.10–1.15) of methyl (meth)acrylate, benzyl methacrylate or styrene containing protected thiol monomers (xanthate and thioacetate vinyl monomers) were obtained via reversible addition–fragmentation chain transfer (RAFT) polymerization. Through aminolysis of the xanthate and thioacetate moieties, copolymers with free thiol moieties were obtained. The thiol bearing polymers were cross-linked with bifunctional acrylates under mild conditions. Precursor polymer dependent size-reductions between 30 and 90% were verified by gel permeation chromatography (GPC) measurements. Furthermore, the SCNPs were characterized by 1H NMR, atomic force microscopy (AFM) and dynamic light scattering (DLS). Characteristic patterns for SCNPs were observed in the AFM phase mode. Thiol-Michael addition is demonstrated to be a versatile tool, which can easily be employed in the preparation of versatile well-defined functional polymer nanoparticles in the 3–10 nm size range

Measurement of branching fractions for exclusive B decays to charmonium final states

We report branching fraction measurements for exclusive decays of charged and neutral B mesons into two-body final states containing a charmonium meson. We use a sample of 22.72 +/- 0.36 million B anti-B events collected between October 1999 and October 2000 with the BABAR detector at the PEP-II storage rings at the Stanford Linear Accelerator Center. The charmonium mesons considered here are J/psi, psi(2S), and chi_c1, and the light meson in We report branching fraction measurements for exclusive decays of charged and neutral B mesons into two-body final states containing a charmonium meson. We use a sample of 22.72 +/- 0.36 million B anti-B events collected between October 1999 and October 2000 with the BABAR detector at the PEP-II storage rings at the Stanford Linear Accelerator Center. The charmonium mesons considered here are J/psi, psi(2S), and chi_c1, and the light meson in the decay is either a K, K^*, or pi^0. the decay is either a K, K^*, or pi^0