Multifunctional Fe3O4@Polydopamine@DNA-Fueled Molecular Machine for Magnetically Targeted Intracellular Zn2+ Imaging and Fluorescence/MRI Guided Photodynamic-Photothermal Therapy.

For the precise treatment of tumors, it is necessary to develop a theranostic nanoplatform that has both diagnostic and therapeutic functions. In this article, we designed a new theranostic probe for fluorescence imaging of Zn2+ and fluorescence/MRI guided magnetically targeted photodynamic-photothermal therapy. The fluorescence imaging of Zn2+ was based on an endogenous ATP-driven DNA nanomachine that could perform repetitive stand displacement reaction. It modifies all units on a single PDA/Fe3O4 nanoparticle containing a hairpin-locked initiated strand activated by a target molecule in cells, a two-stranded fuel DNA triggered by ATP, and a two-stranded DNA track responding to an initiated strand and fuel DNA. After entering the cell, the intracellular target Zn2+ initiates the nanomachine via an autocatalytic cleavage reaction, and the machine programmatically and gradually runs on the assembled DNA track via fuel DNA driving and the intramolecular toehold-mediated stand displacement reaction. The Fe3O4 core first exhibits magnetic targeting, increasing the ability of nanoparticles to enter tumor cells at the tumor site. The Fe3O4 could also be employed as a powerful magnetic resonance imaging (MRI) contrast agent and guided therapy. Using 808 nm laser and 635 nm laser irradiation together at the tumor site, the PDA nanoshell produced an excellent photothermal effect and the TMPyP4 molecules entering the cell generated reactive oxygen species, followed by cell damage. A series of reliable experiments suggested that the Fe3O4@PDA@DNA nanoprobe showed superior fluorescence specificity, MRI, a remarkable photothermal/photodynamic therapy effect, and favorable biocompatibility. This theranostic nanoplatform offered a split-new insight into tumor fluorescence and MRI diagnosis as well as effective tumor therapy.

Molecular Structure of Glycogen in Escherichia coli.

Glycogen, a randomly branched glucose polymer, provides energy storage in organisms. It forms small ß particles which in animals bind to form composite α particles, which give better glucose release. Simulations imply ß particle size is controlled only by activities and sizes of glycogen biosynthetic enzymes and sizes of polymer chains. Thus, storing more glucose requires forming more ß particles, which are expected to sometimes form α particles. No α particles have been reported in bacteria, but the extraction techniques might have caused degradation. Using milder glycogen extraction techniques on Escherichia coli, transmission electron microscopy and size-exclusion chromatography showed α particles, consistent with this hypothesis for α-particle formation. Molecular density and size distributions show similarities with animal glycogen, despite very different metabolic processes. These general polymer constraints are such that any organism which needs to store and then release glucose will have similar α and ß particle structures: a type of convergent evolution.

Microporous polymer based on the new compound "bi-(4-vinyl phenylquinoline) amide" for enrichment and quantitative determination of lamotrigine in rat and human serum.

Lamotrigine is one of the most widely used antiepileptic drugs in the treatment of epilepsy. This kind of drug needs to be used in the long term and should be quantitatively detected in the blood of patients to avoid drug toxicity caused by individual differences and environmental and pathological changes in the process of taking. The detection of antiepileptic drugs in human blood is challenging because of their low contents and the interference of complex matrices. Thus, the sample enrichment method has been commonly used to improve the sensitivity of detection. In this work, we have synthesized a new "bi-(4-vinyl phenylquinoline) amide" compound and used it as the monomer to produce the hyper-cross-linked microporous polymer for the enrichment of lamotrigine. This material has a high adsorption capacity, specificity, and linearity, which can improve the detection sensitivity of lamotrigine by high-performance liquid chromatography (HPLC). The mechanism of this phenomenon has also been investigated. Finally, we have developed the microporous polymer enrichment coupled with HPLC method for the quantitative determination of lamotrigine in rat and human serum samples. This method has excellent precision, accuracy, and recovery, meeting the test of biological sample. The low limit of quantitation was 0.625 µg/mL. Graphical abstract.

Enrichment and Quantitative Determination of 5-(Hydroxymethyl)-2'-deoxycytidine, 5-(Formyl)-2'-deoxycytidine, and 5-(Carboxyl)-2'-deoxycytidine in Human Urine of Breast Cancer Patients by Magnetic Hyper-Cross-Linked Microporous Polymers Based on Polyionic Liquid.

5-(Hydroxymethyl)-2'-deoxycytidine (5-hmdC), 5-(formyl)-2'-deoxycytidine (5-fodC), and 5-(carboxyl)-2'-deoxycytidine (5-cadC) are crucial intermediate products of the DNA demethylation pathway, which can also act as potential biomarkers reflecting the diagnosis and prognosis in multiple tumors. Detecting 5-hmdC, 5-fodC, and 5-cadC in human urine has various advantages including readily available samples and being noninvasive to patients. However, few works have reported the detection of 5-fodC and 5-cadC due to their trace amounts. Here we developed a novel magnetic hyper-cross-linked microporous polymer (HMP) material based on polyionic liquid (PIL) for the enrichment of 5-hmdC, 5-fodC, and 5-cadC. These magnetic PIL-HMP materials provided specific enrichment superiority for three modified cytidines. After enrichment, the signal intensity of 5-hmdC, 5-fodC, and 5-cadC increased 10-75-fold with lower limits of quantitation (LLOQ) of 0.049, 0.781, and 0.781 ng/mL, respectively. The recoveries were approximately 86.5-95.2% for 5-hmdC, 95.2-107.8% for 5-fodC, and 99.4-102.4% for 5-cadC under the relative standard deviation (RSD) of 0.2-10.3%. Finally, we successfully applied magnetic PIL-HMP materials coupled with high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) in enrichment and quantitative determination of 5-hmdC, 5-fodC, and 5-cadC in human urine of 10 breast cancer patients and 10 healthy people. We found that the level of 5-hmdC decreased in breast cancer patients ( p < 0.05), while the levels of 5-fodC and 5-cadC increased ( p < 0.05, p < 0.01). Our results demonstrated that the levels of metabolic 5-hmdC, 5-fodC, and 5-cadC in human urine are closely related to breast cancer, which could contribute to the clinical diagnosis and investigation of breast cancer and its occurrence and development mechanisms.

Preparation of pH-stimuli-responsive PEG-TGA/TGH-capped CdTe QDs and their application in cell labeling.

A pH-sensitive and double functional nanoprobe was designed and synthesized in a water-soluble system using thioglycolic acid (TGA) and mercapto-acetohydrazide (TGH) as the stabilizers. TGA is biocompatible because the carboxyl group is easily linked to biological macromolecules. At the same time, the hydrazide on TGH reacts with the aldehyde on poly(ethylene glycol) (PEG) and forms a hydrazone bond. The hydrazone bond ruptured at specific pH values and exhibited pH-stimuli-responsive characteristics. As an optical imaging probe, the PEG-TGA/TGH-capped CdTe quantum dots (QDs) had high quality, with a fluorescence efficiency of 25-30%, and remained stable for at least five months. This pH-responsive factor can be used for the effective release of CdTe QDs under the acidic interstitial extracellular environment of tumor cells. This allows the prepared pH-stimuli-responsive nanoprobes to show fluorescence signals for use in cancer cell imaging.

Synthesis of Molecularly Imprinted Polymers Based on a New Monomer "2-(4-Vinylphenyl) Quinoline-4-Carboxylic Acid" for the Selective Solid-Phase Extraction of Lamotrigine.

A new molecularly imprinted polymers (MIPs) have been prepared for the high selective extraction of lamotrigine (LTG), a widely used antiepileptic drug, in human serum. The MIPs were polymerized by bulk polymerization using our synthesized compound, 2-(4-vinylphenyl) quinolin-4-carboxylic acid, as functional monomer, which achieved better adsorption specificity than universal MIPs. Then, the molecularly imprinted solid phase extraction (MISPE) based on this material was coupled with high-performance liquid chromatography (HPLC) for the detection of LTG in human serum. The results of method validation showed that the developed method presented a good precision and accuracy, and the linearity was in the range of 1.50-40.00 mg/mL with the limit of quantitation (LOQ) at 0.20 mg/mL. The recovery ranged from 80.8% to 83.8% with RSD ranges from 5.5% to 11.1%. The validated method was successfully used to determine the concentration of LTG in human simulate serum samples.

Functional and biocompatible polymeric ionic liquid (PIL) - Decorated immunomagnetic nanospheres for the efficient capture of rare number CTCs.

This work demonstrated an effective strategy for the capture, identification and determination of multiple types of circulating tumor cells (CTCs) on functional and biocompatible immunomagnetic nanosphere interfaces (IMNs). The IMNs were achieved by functionalizing superparamagnetic iron oxide nanospheres (Fe3O4) with polymerized ionic liquid (PIL), and then coating with epithelial-cell-adhesion-molecule antibody (anti-EpCAM). The IMNs exhibited outstanding cell capture efficiency (above 95%) and specificity when employed to separate multiple EpCAM-positive tumor cells, due to the abundant carboxyl groups in the structure of PIL, which enhanced the coupling efficiency of MNs with anti-EpCAM by chemical bonding between carboxyls and amines, thereby enabling more target cells adhered onto IMNs. Under the optimized capture conditions, IMNs were shown an excellent cell capture performance in the range of 5-400 cells/mL in three different cases (e.g., PBS, MCF-7 and THP-1 mixed cell suspension, lysed blood). More significantly, our results indicated that with modification of PIL, in addition to the capture efficiency, the cell viability rate of CTCs was also greatly improved (98%) owing to the nontoxic and biocompatible properties of PIL, which realized the proliferation of the rare number CTCs for further molecular characterization. Finally, the IMNs were successfully applied to the isolation and detection of CTCs in cancer patient peripheral blood samples and as low as one CTC in the whole blood was captured and identified by the ICC method.