Simple Synthesis of Cladribine-Based Anticancer Polymer Prodrug Nanoparticles with Tunable Drug Delivery Properties

Polymer prodrugs based on cladribine (CdA) as an anticancer drug have been prepared by growing short, well-defined polyisoprene (PI) chains (with number-average molar mass = 1420–4980 g mol^–1 and dispersity = 1.09–1.20) from CdA-bearing alkoxyamine by nitroxide-mediated polymerization. Nanoparticles were formed by nanoprecipitation into water of the resulting <b>CdA-PI</b> conjugates and exhibited long-term colloidal stability in different media, tunable colloidal characteristics, drug release profiles, and anticancer activities <i>in vitro</i>, simply by modulating the drug/polymer linker, the polymer chain length and the formulation parameters. No obvious <i>in vivo</i> toxicity to mice was observed following repeated intravenous injections

2,2′-Biimidazole-Based Conjugated Polymers as a Novel Fluorescent Sensing Platform for Pyrophosphate Anion

Three novel conjugated polymers based on 2,2′-biimidazole have been successfully designed and synthesized through the Suzuki coupling reactions, and their fluorescence sensing ability to metal ions and anions was investigated. The emission of the two polymers with hydrophilic side chains can be efficiently quenched by Cu²⁺ through a photoinduced electron transfer process. Moreover, the polymer–Cu²⁺ complexes exhibit excellent “turn on” sensing properties for detection of pyrophosphate (PPi) anion. These complex sensors possess high selectivity avoiding the interference from other anions, very fast response (less than 3 min) to PPi, and the detection limit of about 0.17 ppm. In addition, the linear detection range of PPi can be tuned conveniently by changing the amount of Cu²⁺ ions. Thus, the conjugated polymers can be used as a novel fluorescent sensing platform, and this work provides a new strategy for the development of PPi sensors

Effect of the deletion of MprF2 on resistance to opsonophagocytosis.

<p>Opsonophagocytic killing of the wild type (12030), 12030<i>ΔmprF2</i> and 12030<i>ΔmprF2</i> CM with serum against anti-LTA (serum-dilution of 1∶1,200).</p

Primers used in this study.

a<p>Linkers are underlined.</p

Enterococcal strains and plasmids used in this study.

<p>Enterococcal strains and plasmids used in this study.</p

Activities of cationic antimicrobial peptides against the <i>E. faecalis</i> 12030 wild type, the deletion mutants and the complemented strain.

<p>Activities of cationic antimicrobial peptides against the <i>E. faecalis</i> 12030 wild type, the deletion mutants and the complemented strain.</p

Measurement of eDNA in biofilms.

<p>All strains (12030, 12030<i>ΔmprF1</i>, 12030<i>ΔmprF2</i>, 12030<i>ΔmprF2</i> CM, 12030<i>ΔmprF2</i> pMSP3535::mprF2) were cultivated overnight in TSB at 37°C and measured with excitation wavelength at 485 nm and emission wavelength at 535 nm. *indicates statistical significance at p<0.05.</p

Effect of the deletion of the MprF2 on virulence in mice.

<p>1.5×10⁸ CFU bacteria were injected in the tail vein of mice. Animals were sacrificed after 48 h, and colony counts were enumerated in liver, kidney and spleen.</p

Biofilm production of the wild type and its derivate mutants.

<p><i>E. faecalis</i> 12030, mutants 12030<i>ΔmprF2</i>1 and 12030<i>ΔmprF2</i> and complemented strains 12030<i>ΔmprF2</i> CM and 12030<i>ΔmprF2 P3535::mprF2</i> were cultivated in TSB media supplemented with 1% glucose. Bacteria were incubated for 18 h, unbound cells were removed by washing of the plates with buffer, and biofilm was stained with crystal violet. Error bars represent standard error of the mean.</p

Tunable Ratiometric Fluorescence Sensing of Intracellular pH by Aggregation-Induced Emission-Active Hyperbranched Polymer Nanoparticles

Recently, ratiometric pH nanosensors have emerged as a robust tool for the fluorescence sensing and imaging, but there is no report of ratiometric sensors based on hyperbranched polymers for intracellular pH sensing. Herein, we describe the first example of hyperbranched polymer-based tunable fluorescent pH nanosensor with aggregation-induced emission activity, which exhibits great potential for ratiometric sensing of intracellular pH. These polymer nanoparticles can selectively accumulate in the acidic organelles of living cells by endocytosis process, and no obvious cytotoxicity was observed. The quantitative analysis of the intracellular pH values in HeLa cells was successfully conducted based on this new sensing platform. This platform provides a new choice for future developments of ratiometric fluorescent nanosensors, targeting not only protons but also a variety of other analytes of biological interest, such as metal ions, anions, and other biomolecules