One Stone, Three Birds: Design and Synthesis of "All-in-One" Nanoscale Mn-Porphyrin Coordination Polymers for Magnetic Resonance Imaging-Guided Synergistic Photodynamic-Sonodynamic Therapy.

Multifunctional nanomaterials with potential applications in both bioimaging and photodynamic-sonodynamic therapy have great advantages in cancer theranostic, but the design and preparation of "all-in-one" type of multifunctional nanomaterials with single component remains challenging. Herein the "all-in-one" type of Mn-PpIX (Protoporphyrin IX) coordination polymers (MnPPs) was reported as efficient nano-photo/sonosensitizers. The MnPPs had an average size of âˆ¼ 110 nm. Upon light/US (ultrasound) irradiation for 5 min, 61.8 % (light) and 32.4 % (US) of DPBF (1.3-diphenyl isobenzofuran) was found to be oxidized by MnPPs, which showed effective ROS (reactive oxygen species) generation for photodynamic/sonodynamic therapy (PDT/SDT). In addition, MnPPs revealed excellent biosafety and could be engulfed by cells to produce intracellular ROS under light/US excitation for efficient killing tumor cells. When MnPPs was injected into mice, the tumor could be monitored via MRI (magnetic resonance imaging). In addition, tumor growth could be significantly inhibited by the synergistic PDT-SDT. Therefore, the present study not only represents MnPPs as an "all-in-one" type of multifunctional nanomaterials for MRI-guided PDT-SDT therapy, but also provides some insights for designing other PpIX-related molecules with the similar structure for bioapplication.

From biomaterials to biotherapy: cuttlefish ink with protoporphyrin IX nanoconjugates for synergistic sonodynamic-photothermal therapy.

Biologically produced nanomaterials capable of therapeutic purposes have received increasing interest in tumor therapy because of their intrinsic biocompatibility. In this study, we made cuttlefish ink (extracted from cuttlefish) and protoporphyrin IX (PpIX) nanoconjugates (CIPs) where PpIX was an endogenous organic compound. In the case of CIPs, PpIX could be triggered by ultrasound (US) for sonodynamic therapy (SDT), and the cuttlefish ink could be excited by a near-infrared laser for photothermal therapy (PTT). Thereafter, tumor growth was greatly inhibited through synergistic SDT-PTT in comparison to single SDT or PTT. In addition, in vivo administration of CIPs showed no noticeable side effects for mouse blood and chief organs, providing an effective strategy for developing biologically produced biomaterials and using them for biotherapy.

Ratiometric fluorescence chemodosimeter for hydrazine in aqueous solution and gas phase based on Quinoline-Malononitrile.

The widespread use of Hydrazine (N2H4) in many areas of the chemical industry, brings potential risks to human health and environmental pollution. To detect N2H4 effectively, a simple ratio fluorescence probe (QMM), designed and synthesized through Vilsmeier reaction and Knoevenagel reaction, was prepared for the specific response of N2H4 based on the irreversible chemical reaction. The ratiometric fluorescence chemodosimeter displayed a response for hydrazine with high selectivity, sensitivity and anti-interference ability. The measured detection limit is 38.30 nm (0.122 ppb), which is far lower than the maximum allowable level of the U.S. Environmental Protection Agency (10 ppb). Moreover, test paper and TLC plates loading QMM had been made, which could be utilized to detect hydrazine both in aqueous solution samples and in gas phase samples. Thus QMM could serve as an easily manufactured, low-cost, efficient and portable solid-state optical probe to detect hydrazine in field measurements.

Multicolor imaging of hydrogen peroxide level in living and apoptotic cells by a single fluorescent probe.

To understand the entangled relationship between reactive oxygen species (ROS) and apoptosis, there is urgent need for simultaneous dynamic monitoring of these two important biological events. In this study, we have developed a fluorescent probe, pep4-NP1, which can simultaneously detect H2O2 and caspase 3, the respective markers of ROS and apoptosis. The probe contains a H2O2 fluorescence reporter (NP1) and Cy5 fluorescent chromophore connected by a caspase 3 specific recognition peptide. The detecting strategy was realized through a controllable fluorescence resonance energy transfer (FRET) process between NP1 and Cy5 of pep4-NP1, after reaction with H2O2, which was verified by molecular calculation and in vitro spectral studies. In the absent of caspase 3, the accumulation of H2O2 induces red fluorescence of pep4-NP1 centered at 663nm in living cells due to the existence of FRET. In contrast, FRET is inhibited in apoptotic cells due to cleavage of the peptide spacer of pep4-NP1 by over-expressed caspase 3. Consequently, green fluorescence (555nm) predominated when labelling production of H2O2 in apoptotic cells. Moreover, Pep4-NP1 shows excellent selectivity towards H2O2 and caspase 3 on their respective reaction sites. Therefore, pep4-NP1 can distinguish endogenously generated H2O2 between living cells and apoptotic cells with different fluorescence wavelengths, providing additional information on the ROS production pathways.

A highly sensitive ratiometric fluorescent probe for the detection of cytoplasmic and nuclear hydrogen peroxide.

As a marker for oxidative stress and a second messenger in signal transduction, hydrogen peroxide (H2O2) plays an important role in living systems. It is thus critical to monitor the changes in H2O2 in cells and tissues. Here, we developed a highly sensitive and versatile ratiometric H2O2 fluorescent probe (NP1) based on 1,8-naphthalimide and boric acid ester. In response to H2O2, the ratio of its fluorescent intensities at 555 and 403 nm changed 1020-fold within 200 min. The detecting limit of NP1 toward H2O2 is estimated as 0.17 µM. It was capable of imaging endogenous H2O2 generated in live RAW 264.7 macrophages as a cellular inflammation response, and especially, it was able to detect H2O2 produced as a signaling molecule in A431 human epidermoid carcinoma cells through stimulation by epidermal growth factor. This probe contains an azide group and thus has the potential to be linked to various molecules via the click reaction. After binding to a Nuclear Localization Signal peptide, the peptide-based combination probe (pep-NP1) was successfully targeted to nuclei and was capable of ratiometrically detecting nuclear H2O2 in living cells. These results indicated that NP1 was a highly sensitive ratiometric H2O2 dye with promising biological applications.

Fluorescence turn-on detection of Sn2+ in live eukaryotic and prokaryotic cells.

Sn(2+) is usually added to toothpaste to prevent dental plaque and oral disease. However, studies of its physiological role and bacteriostatic mechanism are restricted by the lack of versatile Sn(2+) detection methods applicable to live cells, including Streptococcus mutans. Here we report two Sn(2+) fluorescent probes containing a rhodamine B derivative as a fluorophore, linked via the amide moiety to N,N-bis(2-hydroxyethyl)ethylenediamine (R1) and tert-butyl carbazate group (R2), respectively. These probes can selectively chelate Sn(2+) and show marked fluorescence enhancement due to the ring open reaction of rhodamine induced by Sn(2+) chelation. The probes have high sensitivity and selectivity for Sn(2+) in the presence of various relevant metal ions. Particularly, both R1 and R2 can target lysosomes, and R2 can probe Sn concentrations in lysosomes with rather acidic microenvironment. Furthermore, these two probes have low toxicity and can be used as imaging probes for monitoring Sn(2+) not only in live KB cells (eukaryotic) but also in Streptococcus mutans cells (prokaryotic), which is a useful tool to study the physiological function of Sn(2+) in biological systems.