Guangyue Zu

A hemin binding G-quadruplex/Pb2+ complex to construct a visible light activated photoelectrochemical sensor on a ZnO/BiOI heterostructure

This study reported the development of a p–n heterojunction photoelectrochemical biosensor using a G-quadruplex as the recognition system. The n-type ZnO nanorods and p-type BiOI nanoflakes were combined to form the heterostructure by in situ growth of BiOI attributed to a simple impregnating-hydroxylation method. This simple p–n heterojunction fabrication method could facilitate the development of rapid and sensitive visible light activated PEC sensors. In this study, the ZnO/BiOI photoelectrode showed a rapid photocurrent decrease in the presence of Pb2+ due to the electron withdrawing effect of hemin which bound with the G-quadruplex/Pb2+ complex. This PEC biosensor exhibited a good response following the concentration of Pb2+ in the range from 10 to 100 μM.

The development of a light-up red-emitting fluorescent probe based on a G-quadruplex specific cyanine dye

A cyanine dye-dimethylindole red containing an extending polymethine chain, a sterically bulky dimethylindole heterocycle and an anionic propylsulfonate substituent on the quinoline ring was found to behave as a high specific light-up G-quadruplex probe in the red-emitting region above 650 nm, especially for parallel G-quadruplex c-myc. The 10 to 70-fold enhancement in the fluorescence quantum yield of dimethylindole red when incubating with G-quadruplexes may benefit more accurate definition of the distribution of G-quadruplexes across the genome.

Poly(glycerol) Used for Constructing Mixed Polymeric Micelles as T1 MRI Contrast Agent for Tumor-Targeted Imaging

There was much interest in the development of nanoscale delivery vehicles based on polymeric micelles to realize the diagnostic and therapeutic applications in biomedicine. Here, with the purpose of constructing a micellar magnetic resonance imaging (MRI) contrast agent (CA) with well biocompatibility and targeting specificity, two types of amphiphilic diblock polymers, mPEG-PG(DOTA(Gd))-b-PCL and FA-PEG-b-PCL, were synthesized to form mixed micelles by coassembly. The nanostructure of the resulting micellar system consisted of poly(caprolactone) (PCL) as core and poly(glycerol) (PG) and poly(ethylene glycol) (PEG) as shell, simultaneously modified with DOTA(Gd) chelates and folic acid (FA), which afforded functions of MRI contrast enhancement and tumor targeting. The mixed micelles in aqueous solution presented a hydrodynamic diameter of about 85 nm. Additionally, this mixed micelles exhibited higher r1 relaxivity (14.01 mM-1 S1-) compared with commercial Magnevist (3.95 mM-1 S1-) and showed negligible cytotoxicity estimated by WST assay. In vitro and in vivo MRI experiments revealed excellent targeting specificity to tumor cells and tissue. Furthermore, considerably enhanced signal intensity and prominent positive contrast effect were achieved at tumor region after tumor-bearing mice were intravenously injected with the mixed micelles. These preliminary results indicated the potential of the mixed micelle as T1 MRI CA for tumor-targeted imaging.

Oligoethylenimine grafted PEGylated poly(aspartic acid) as a macromolecular contrast agent: properties and in vivo studies

PEGylated poly(aspartate-g-OEI) was developed as a magnetic resonance imaging probe. The PEG-PBLA block copolymer was prepared by the ring-opening polymerization of β-benzyl-l-aspartate N-carboxy-anhydride (BLA-NCA) initiated by the terminal primary amino group of mPEG-NH2, followed by grafting with oligoethylenimine (OEI, Mw = 800) and Gd-DTPA. Compared to Gd-DTPA (4.42 mM-1 s-1), PEG-p(Asp-OEI-DTPA-Gd) exhibited much higher T1 relaxivity (19.03 mM-1 s-1), up to 4.3 times higher than Gd-DTPA. No obvious cytotoxicity was observed from the WST assay and H&E analysis, which illustrated that this macromolecular contrast agent (mCA) exhibited excellent biocompatibility. Folic acid (FA) was further labeled onto the mCA to endow the mCA with targeting ability. During in vivo animal studies, the FA labeled MRI probes showed a significant signal intensity enhancement in the tumor during different time intervals and provided a long and efficient window time for MR examination. These results suggest that such mCAs are excellent candidates as magnetic resonance imaging (MRI) probes with high efficiency and safety.

Preparation of linear poly(glycerol) as a T1 contrast agent for tumor-targeted magnetic resonance imaging

Macromolecular contrast agents (CAs) labeled with targeting molecules are gaining remarkable interest as promising materials overcoming the defects of small-molecule CAs. Designed on the basis of biocompatible poly(glycerol) (PG), a linear macromolecular contrast agent (CA) was synthesized with a composition of PG as a backbone and partial hydroxyl connected with gadolinium labeled poly(l-lysine) dendrons, where folic acid was also conjugated. This linear CA exhibited higher relaxivity (7.04 mM-1 S-1) relative to Magnevist® (3.98 mM-1 S-1), and showed negligible toxicity determined by WST assay and histological analysis. In vitro and in vivo magnetic resonance imaging (MRI) measurements presented obvious target specificity to KB cells and tumor. Moreover, high signal enhancement was observed in the tumor region at various time points after intravenous injection to ensure the long time window for imaging. All the findings make it an attractive candidate for tumor-targeted MRI CAs.

Functional Hyperbranched Polylysine as Potential Contrast Agent Probes for Magnetic Resonance Imaging

Researchers have never stopped questing contrast agents with high resolution and safety to overcome the drawbacks of small-molecule contrast agents in clinic. Herein, we reported the synthesis of gadolinium-based hyperbranched polylysine (HBPLL-DTPA-Gd), which was prepared by thermal polymerization of l-lysine via one-step polycondensation. After conjugating with folic acid, its potential application as MRI contrast agent was then evaluated. This contrast agent had no obvious cytotoxicity as verified by WST assay and H&E analysis. Compared to Gd(III)-diethylenetriaminepentaacetic acid (Gd-DTPA) (r1 = 4.3 mM(-1) s(-1)), the FA-HBPLL-DTPA-Gd exhibited much higher longitudinal relaxivity value (r1 = 13.44 mM(-1) s(-1)), up to 3 times higher than Gd-DTPA. The FA-HBPLL-DTPA-Gd showed significant signal intensity enhancement in the tumor region at various time points and provided a long time window for MR examination. The results illustrate that FA-HBPLL-DTPA-Gd will be a potential candidate for tumor-targeted MRI.

Biocleavable Oligolysine-Grafted Poly(disulfide amine)s as Magnetic Resonance Imaging Probes.

To develop safe and effective macromolecular MRI contrast agents, a macromolecular contrast agent (mCA) containing biocleavable disulfide bonds in the main chain and oligolysine in the side chain is prepared, and its applicability as a MRI contrast agent is demonstrated both in vitro and in vivo. This brush-like mCA possesses a high T1 relaxivity (11.8 mM(-1) s(-1)), up to 3 times higher than the commercial Gd-DTPA (4.2 mM(-1) s(-1)), along with very low toxicity as determined by WST assay and histological analysis. Meanwhile, the disulfide bond can be broken under appropriate reducing conditions, followed by degradation into small fragments. Furthermore, the mCA is functionalized with folic acid to improve the target specificity. In vivo experiments show that FA-labeled mCA can efficiently enhance the resolution between the tumor and surrounding tissues compared to the mCA without FA. This study may provide helpful insights for the further development of sensitive and biocompatible MRI probes.

Hyperbranched poly(glycerol) as a T1 contrast agent for tumor-targeted magnetic resonance imaging in vivo

Correction for ‘Hyperbranched poly(glycerol) as a T1 contrast agent for tumor-targeted magnetic resonance imaging in vivo’ by Yi Cao, et al., Polym. Chem., 2017, DOI: 10.1039/c6py01819j.

PEGylated chitosan grafted with polyamidoamine-dendron as tumor-targeted magnetic resonance imaging contrast agent

Macromolecular contrast agents labeled with targeting ligands are now receiving growing interest in tumor-targeted magnetic resonance imaging. In this study, a macromolecular contrast agent based on PEGylated chitosan was synthesized and characterized, and its application as an MRI contrast agent was then demonstrated both in vitro and in vivo. First, the chitosan backbone was partially grafted with poly(ethylene glycol), which was used to improve the in vivo stability, followed by modifying with azide groups. Second, alkynyl-terminated PAMAM dendron modified with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) was synthesized and conjugated onto the chitosan backbone through click chemistry. Finally, the obtained mCA was further functionalized with folic acid to improve the target specificity. The obtained FA labeled mCA exhibited higher relaxivity (9.53 mM−1 s−1) relative to Gd-DTPA (4.25 mM−1 s−1) and showed negligible toxicity as determined by the WST assay. In vivo MRI results suggested that a relatively high signal enhancement was observed in the tumor region, which made it a promising candidate for tumor-targeted MRI CA.

Multi-arm star-branched polymer as an efficient contrast agent for tumor-targeted magnetic resonance imaging

Contrast agents with high efficiency and safety are excellent candidates as magnetic resonance imaging probes. Herein, a multi-arm star-branched polymer was prepared by conjugating oligolysine onto a rigid hyperbranched poly(amido amine) core via click chemistry, followed by covalent modification with Gd chelate and folic acid (FA-OLL-g-HBPAMAM-DTPA-Gd). This multi-arm star-branched polymer contrast agent exhibited much higher longitudinal relaxivity (r1 = 13.34 mM-1 s-1) as compared to a commercial contrast agent (Gd-DTPA, r1 = 4.2 mM-1 s-1). No obvious histological toxicity was observed from histological assessment, which illustrated that FA-OLL-g-HBPAMAM-DTPA-Gd exhibited excellent biocompatibility. Both in vitro and in vivo MRI studies showed that the macromolecular contrast agent provided better signal contrast enhancement and presented obvious target specificity to KB xenografts with a sufficient time window for MRI scanning; moreover, this multi-arm star-branched mCA has great potential for developing sensitive and biocompatible MRI CA with targeting ability.