Kunchi Zhang

915 nm Light-Triggered Photodynamic Therapy and MR/CT Dual-Modal Imaging of Tumor Based on the Nonstoichiometric Na0.52YbF3.52:Er Upconversion Nanoprobes

Lanthanide (Ln(3+) )-doped upconversion nanoparticles (UCNPs) as a new generation of multimodal bioprobes have attracted great interest for theranostic purpose. Herein, red emitting nonstoichiometric Na0.52 YbF3.52 :Er UCNPs of high luminescence intensity and color purity are synthesized via a facile solvothermal method. The red UC emission from the present nanophosphors is three times more intense than the well-known green emission from the ≈30 nm sized hexagonal-phase NaYF4 :Yb,Er UCNPs. By utilizing Na0.52 YbF3.52 :Er@SrF2 UCNPs as multifunctional nanoplatforms, highly efficient in vitro and in vivo 915 nm light-triggered photodynamic therapies are realized for the first time, with dramatically diminished overheating yet similar therapeutic effects in comparison to those triggered by 980 nm light. Moreover, by virtue of the high transverse relaxivity (r 2 ) and the strong X-ray attenuation ability of Yb(3+) ions, these UCNPs also demonstrate good performances as contrast agents for high contrast magnetic resonance and X-ray computed tomography dual-modal imaging. Our research shows the great potential of the red emitting Na0.52 YbF3.52 :Er UCNPs for multimodal imaging-guided photodynamic therapy of tumors.

Aptamer-Modified Temperature-Sensitive Liposomal Contrast Agent for Magnetic Resonance Imaging

A novel aptamer modified thermosensitive liposome was designed as an efficient magnetic resonance imaging probe. In this paper, Gd-DTPA was encapsulated into an optimized thermosensitive liposome (TSL) formulation, followed by conjugation with AS1411 for specific targeting against tumor cells that overexpress nucleolin receptors. The resulting liposomes were extensively characterized in vitro as a contrast agent. As-prepared TSLs-AS1411 had a diameter about 136.1 nm. No obvious cytotoxicity was observed from MTT assay, which illustrated that the liposomes exhibited excellent biocompatibility. Compared to the control incubation at 37 °C, the liposomes modified with AS1411 exhibited much higher T1 relaxivity in MCF-7 cells incubated at 42 °C. These data indicate that the Gd-encapsulated TSLs-AS1411 may be a promising tool in early cancer diagnosis.

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.

Phosphorylation triggered poly-nanoparticle assembly for naked-eye distinguishable T4 polynucleotide kinase detection

A novel naked-eye distinguishable nanosensor based on phosphorylation triggered poly-nanoparticle assembly strategy has been designed for detecting T4 PNK activity. This colorimetric sensor exhibits conveniently homogeneous operation with simple, sensitive and easily scalable properties.

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.

Modeling the relationship between melting point of a metal nanowire and its cap surface curvature

It is of practical importance to predict the melting point of metal nanowires in a confined environment. Based on molecular dynamics (MD) simulations, a universal model unravelling the relationship between the melting point of a metal nanowire in nanoconfinement and its cap surface curvature has been developed for the first time. The results have demonstrated that both the interaction strength between the nanowire and the nanoconfinement and the diameter of nanoconfinement dramatically affect the melting point of the embedded nanowire. These phenomena can be further expressed in a mathematical formula directly describing the curvature-dependent melting point. It is also found that the melting feature of the metal nanowire under weak interaction is quite different from that under strong interaction. Furthermore, the melting point of the free cluster can also be predicted using this model. Our findings have provided a direct way to analyze the melting point via the observed morphology of the metal nanoparticle.

Oligoethylenimine-grafted chitosan as enhanced T1 contrast agent for in vivo targeted tumor MRI.

To synthesize and characterize an effective macromolecular magnetic resonance imaging (MRI) contrast agent based on oligoethylenimine‐grafted chitosan with targeting capability.