Bacterium-Sculpted Porphyrin-Protein-Iron Sulfide Clusters for Distinction and Inhibition of Staphylococcus aureus.

Microbe-catalyzed surface modification is a promising method for the production of special targeting nanomaterials. A bacterium-selective material can be obtained by investigating the microbe-catalyzed mineralization of proteins. Herein, a novel method was fabricated for the biosynthesis of FeS-decorated porphyrin-protein clusters (P-CA@BE) via E. coli (Escherichia coli)-catalyzed bio-Fe(III) reduction and bio-sulfidation of porphyrin (P), caffeic acid (CA), and protein [bovine serum albumin (BSA)] assemblies. The assembly (P-CA@BSA) was identified by spectroscopic methods. Next, the P-CA@BSA assembly was transferred into FeS-decorated porphyrin-protein clusters (P-CA@BE) catalyzed by E. coli. There are partial ß-folding proteins in P-CA@BE, which selectively recognize S. aureus (Staphylococcus aureus) and show different antibacterial properties against E. coli and S. aureus. Results demonstrate that the E. coli-catalyzed mineralization of the porphyrin-protein assembly is an effective method for the biosynthesis of S. aureus-sensitive metal-protein clusters.

Total femur replacement with 18 years of follow-up: A case report.

BACKGROUND: Osteosarcoma is one of the most common primary malignant bone tumors and is more common in adolescents. The femur is the most common site of osteosarcoma, and many patients require total femur replacement. We reviewed the relevant literature and case findings, summarized and analyzed this case in combination with relevant literature, and in doing so improved the understanding of the technology. CASE SUMMARY: The case we report was a 15-year-old patient who was admitted to the hospital 15 days after the discovery of a right thigh mass. The diagnosis was osteosarcoma of the right femoral shaft. After completion of neoadjuvant chemotherapy and preoperative preparation, total right femoral resection + artificial total femoral replacement was performed. Then, chemotherapy was continued after surgery. The patient recovered well after treatment, and the function of the affected limb was good. No recurrence, metastasis, prosthesis loosening, dislocation, fracture or other complications were found during 18 years of follow-up. At present, the patient can still work and lives normally. The results of the medium- and long-term follow-up were satisfactory. CONCLUSION: Artificial total femur replacement is a feasible limb salvage operation for patients with femoral malignant tumors, and the results of medium- and long-term follow-up are satisfactory.

A dye-andrographolide assembly as a turn-on sensor for detection of phthalate in both cells and fish.

Phthalates can penetrate the environment and enrich various aquatic organisms through the food chain, which is involved in promoting the growth of breast cancer. It is of current interest to develop new sensors for phthalates. We herein reported a hydrogen-bond competing fluorescent sensor, BANP, for the detection of dibutyl phthalate (DBP). The BANP compound was synthesized by assembling andrographolide (Andro), nitro- and cyano-substituted BODIPY dye (BCN), and polyethylene glycol derivatives (DSPE-mPEG5000). BANP was found to be a turn-on fluorescent probe for DBP in water with a detection limit of 0.13 µg/g; the DBP-water system acts as a hydrogen bond switch to turn on the fluorescence. And BANP fluorescently detected DBP in contaminated fish meat. Moreover, BANP sensed the DBP-induced growth of human breast cancer MCF-7 cells, and the release of Andro in the DBP-cultivated cancer cells inhibited the proliferation of the MCF-7 cells. Taken together, BANP is a DBP-responsive probe for sensitive DBP detection in water, cells, and fish meats. The BANP sensor may be used in both in vitro fluorescence and cellular imaging analyses. Our results show that guest-induced reassembly brings forth significant fluorescence change, which is a promising way of designing new fluorescent probes for the analysis of phthalates in the environment and food.

Structure and biomolecular recognition of nitro-BODIPY-andrographolide assembles for cancer treatment.

Andrographolide (Andro) derivatives can interfere with a variety of enzymes. To increase the cancer cell absorption of Andro and to enhance the therapeutic effect of breast cancer, nitro group substituted boron dipyrromethene (NBDP) was used as the carrier of Andro. Two NBDP based assemblies (NBDP-Andro and nano NBDPAndro@PEG) were synthesized and characterized by spectroscopic methods. The affinity of Andro with NBDP enhanced the emission of NBDP. The interaction of the compounds with lipase was also studied. NBDP-Andro can bind with lipase and form new species with an emission at 360 nm. Results demonstrate that the Andro of NBDP-Andro drives the interaction of compounds with protein (BSA) and lipase by inter-molecular forces. The large red shift emission at 611 nm of the NBDPAndro@PEG is observed and discussed. Also, the MTT assay confirms that Nano NBDPAndro@PEG can enhance the inhibition rate of the proliferation of MCF-7 breast cancer cells. Therefore, nitro substituted BODIPY can be a carrier of andrographolide for cancer treatment.

Nano adamantane-conjugated BODIPY for lipase affinity and light driven antibacterial.

The increasing number of resistant bacterial strains has raised efforts in developing alternative treatment strategies. Lipase is highly expressed in most bacteria and lipase targeting dyes will be non-sacrificed materials for a sustainable method against microorganism. The combination of chemotherapy and antimicrobial photodynamic inactivation (aPDI) method will be an effective method due to enhanced antibacterial activity. Here we reported the spectroscopic features of five boron dipyrrolylmethene (BODIPY) derivatives with different functional groups for lipase affinity and antibacterial activity. Lipase affinity tests and antibacterial assays were conducted by spectroscopic methods. Adamantane-conjugated BODIPY (BDP-2) was found to be the active compound against E. coli. Next, BDP-2 was brominated, and then assembled with PEG resulting biocompatible BDP2-Br2@mPEG nanoparticles. The MTT assay indicated that BDP2-Br2@mPEG was less toxicity on BGC-823 cancer cells without irradiation. The BDP2-Br2@mPEG can inhibit the proliferation of E. coli and damage the membrane of bacterial cell under green LED light irradiation. The results proved BDP2-Br2@mPEG can be a very promising green LED light driven antibacterial material.

Mitochondrial targeting nano-curcumin for attenuation on PKM2 and FASN.

Tumor cells are sensitive to the disturbance of mitochondrial functions. Attenuation of dysfunctional mitochondria by natural compounds is an emerging strategy for the recovery of abnormal energy metabolism of cancer. To develop a nano-sized curcumin (CUR) in attenuating the energy metabolism of cancer cells, herein, a coral-shaped nano-transporter DNA-FeS2-DA nanoparticle was synthesized using double-stranded DNA rich in 'GAG' and 'GC' series as a template and poly-dopamine as an adhesive. CUR was successfully loaded to DNA-FeS2-DA with a molar ratio of ssDNA: CUR of 1:16, forming CUR@DNA-FeS2-DA. This nano-curcumin can readily enter mitochondrion in MCF-7 cancer cells. The CUR@DNA-FeS2-DA nanocomposite displays desirable photothermal effect and stability, while its CUR can be released gradually in the weak acid environment. The expression of both pyruvate kinase M2 and fatty acid synthase in the MCF-7 cancer cells were noticeably inhibited by CUR@DNA-FeS2-DA. Given the controlled release and mitochondria-targeting properties, this CUR@DNA-FeS2-DA nanocomposite is a promising new drug entity for intervening the energy metabolism of cancer cells.

The NIR inspired nano-CuSMn(II) composites for lactate and glycolysis attenuation.

The level of lactate and hypoxia inducible factor (HIF) in cells has effect on tumor growth and drug resistance. The glycolysis of tumors could be inhibited by reducing the expression of lactate dehydrogenase A (LDHA) or the mutual conversion of lactic acid and pyruvic acid. To develop a bifunctional nanoparticle as both the cleaner of lactate and attenuator of glycolysis, a NIR (near infrared) responsive nanoparticle (Mn-CuS@BSA-FA) was synthesized and characterized. The Mn-CuS@BSA-FA catalyzed the oxidation of lactate to pyruvate under NIR irradiation. In vitro assay results demonstrate that Mn-CuS@BSA-FA can decrease the activity of LDHA and attenuate the conversion of lactate to pyruvate. Moreover, Mn-CuS@BSA-FA can inhibit the expression of HIF-1 and decrease the ATP level in HepG-1 cells. Our work demonstrates that Mn-CuS@BSA-FA can be a NIR enhanced glycolytic inhibitor for cancer interventional treatment.

Biocompatible G-Quadruplex/BODIPY assembly for cancer cell imaging and the attenuation of mitochondria.

The G-quadruplex aptamer is a high-order structure formed by folding of guanine-rich DNA or RNA. The recognition and assembly of G-quadruplex and compounds are important to find biocompatible drugs. Herein, triphenylamine conjugated 4, 4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) compound (BPTPA) was synthesized, and the interaction of BPTPA with G4 DNA was studied. It is found that BPTPA selectively binds with G3T3 G4 DNA forming a water-compatible nanocomplex (BPTPA-G3T3). BPTPA-G3T3 can image mitochondria and inhibit the expression of TrxR2. Cytotoxicity results indicate BPTPA-G3T3 can decrease the membrane potential of mitochondria and inhibit the proliferation of BGC-823 cancer cells. Therefore, BPTPA-G3T3 can be the biocompatible attenuator of mitochondria for cancer image and chemotherapy.

A NIR-BODIPY derivative for sensing copper(II) in blood and mitochondrial imaging.

In order to develop NIR BODIPY for mitochondria targeting imaging agents and metal sensors, a side chain modified BODIPY (BPN) was synthesized and spectroscopically characterized. BPN has NIR emission at 765nm when excited at 704nm. The emission at 765nm responded differently to Cu2+ and Mn2+ ions, respectively. The BPN coordinated with Cu2+ forming [BPNCu]2+ complex with quenched emission, while Mn2+ induced aggregation of BPN with specific fluorescence enhancement. Moreover, BPN can be applied to monitor Cu2+ in live cells and image mitochondria. Further, BPN was used as sensor for the detection of Cu2+ ions in serum with linear detection range of 0.45µM-36.30µM. Results indicate that BPN is a good sensor for the detection of Cu2+ in serum and image mitochondria. This study gives strategies for future design of NIR sensors for the analysis of metal ions in blood.

An aptamer-Fe3+ modified nanoparticle for lactate oxidation and tumor photodynamic therapy.

To develop a cancer targeting lactate attenuator in vivo for cancer phototherapy and inhibition of HIF-1, we report an aptamer modified photo-responsive nanoparticle (labeled as Mn-D@BPFe-A) for lactate oxidation and cancer phototherapy. Mn-D@BPFe-A was constructed by the assembly of functional complex with BSA, followed by surface metal coordination and the recognition of Fe3+ with GAG containing sequence. Upon irradiation, Mn-D@BPFe-A NPs can oxidize water with the generation of OH, which convert lactate into pyruvate both in vitro and in vivo. Obviously, the Mn-D@BPFe-A exhibits a significant tumor ablation owing to the light driven oxidation of lactic acid and dysfunction of mitochondria. Importantly, it can decrease both the level of lactate in cancer tissues and the expression of HIF-1α and Glut-1 in HepG-2 cells. These results demonstrated that oxidation of lactate with dysfunction of mitochondria by nucleic acid-Fe3+ modified nanoparticle is an effective strategy for the development of non-oxygen dependent photodynamic effect agents.

A near-infrared BSA coated DNA-AgNCs for cellular imaging.

Near-infrared silver nanoclusters, have potential applications in the field of biosensing and biological imaging. However, less stability of most DNA-AgNCs limits their application. To obtain stable near-infrared fluorescence DNA-AgNCs for biological imaging, a new kind of near-infrared fluorescent DNA-Ag nanoclusters was constructed using the C3A rich aptamer as a synthesis template, GAG as the enhancer. In particular, a new DNA-AgNCs-Trp@BSA was obtained based on the self-assembly of bovine serum albumin (BSA) and tryptophan loaded DNA-AgNCs by hydrophobic interaction. This self-assembly method can be used to stabilize DNAn-Ag (n = 1-3) nanoclusters. Hence, the near-infrared fluorescence DNA-AgNCs-Trp@BSA was applied in cellular imaging of HepG-2 cells.

Smart Magnetic Nanoaptamer: Construction, Subcellular Distribution, and Silencing HIF for Cancer Gene Therapy.

Attenuating the expression of HIF-1α (hypoxic inducible factor) by siRNA has an effect on the proliferation of hypoxia cancers. Mitochondria targeting siRNA may silence the level of HIF-1α for cancer gene therapy. A GAG-rich DNA was conjugated to GC-rich DNA for the synthesis of functional magnetic nanoaptamer (DNA-Fe3O4) to keep the innate character of the targeting aptamer. The DNA-Fe3O4 can load the hydrophobic dye (BODIPY-OCH3) by the GC-rich sequences, resulting in fluorescent nanoaptamer (BFe@DNA). Self-assembly of BFe@DNA with target aptamer resulted in the formation of BFe@DNAH. Subcellular fluorescence imaging results confirm that BFe@DNAH can accumulate in MCF-7 cells and selectively target mitochondrion. In particular, BFe@DNAH can transport siRNA to breast cancer cells or tissues for the attenuation of HIF-1α and ATP and the inhibition on growth of cancer cells in vivo. Therefore, BFe@DNAH is a smart nanoaptamer platform for the development of subcellular imaging agents and gene therapy.

Characterization, catalyzed water oxidation and anticancer activities of a NIR BODIPY-Mn polymer.

To obtain near-IR absorbing biomaterials as fluorescence cellular imaging and anticancer agents for hypoxic cancer cell, a nano NIR fluorescence Mn(III/IV) polymer (PMnD) was spectroscopically characterized. The PMnD shows strong emission at 661nm when excited with 643nm. Furthermore, PMnD can catalyze water oxidation to generate dioxygen when irradiated by red LED light (10W). In particular, the PMnD can enter into HepG-2 cells and mitochondria. Both anticancer activity and the inhibition of the expression of HIF-1α for PMnD were concentration dependent. Our results demonstrate that PMnD can be developed as mitochondria targeted imaging agents and new inhibitors for HIF-1 in hypoxic cancer cells.

BODIPY-Mn nanoassemblies for accurate MRI and phototherapy of hypoxic cancer.

Hypoxia promotes not only the metastasis of tumors but also therapeutic resistance. Photosensitizer-mediated consumption of O2 during photodynamic therapy (PDT) reinforces tumor hypoxia. Herein, a light-dependent attenuator of a hypoxic environment is reported for accurate MRI and phototherapy of hypoxic cancer. First, a photoresponsive Mn(ii) nanoassembly was constructed, then it was assembled with bovine serum albumin (BSA) and modified with polyethylene glycol-folic acid (PEG-FA), forming cancer targeting Mn-DBA@BSA-FA nanoassemblies, which offer T1 signals and can catalyze the water oxidation reaction under irradiation of red light emitting diode (LED) light with the generation of O2 and heat. Moreover, they could selectively penetrate through and accumulate in the tumor tissues with clear T1 magnetic resonance imaging (MRI) signals, and have remarkably eliminated the tumors in vivo, while they are of low toxicity to the healthy organs. The release of the Mn(ii) complex from the nanoparticles in an acidic environment and the in vivo biodistribution results confirm the selective cancer targeting. Our work demonstrates the potential of nanoparticles as excellent theranostic agents for MR imaging combined with phototherapy triggered by near-infrared light.

A mitochondria targeting Mn nanoassembly of BODIPY for LDH-A, mitochondria modulated therapy and bimodal imaging of cancer.

HIF-1α and LDH-A are important targets for hypoxia-driven drug resistance. Mitochondria targeted fluorescent manganese(II)-complexes can be used as potential fluorescence imaging agents, MRI contrast agents and HIF-1α and LDH-A involved anticancer complexes. In this study, a fluorescent manganese(II) nanoparticle, labeled as (PEG-Mn-BDA), was synthesized and used as both fluorescent and MRI imaging agents in cancer cells. In vitro bioassay results indicate that PEG-Mn-BDA was able to inhibit LDH-A activity and depolarize mitochondrial membrane potential with the generation of intracellular ROS, which contributed to the induction of apoptosis. Moreover, the pro-apoptotic protein, caspase 3 was highly expressed. In vivo, PEG-Mn-BDA could also exert inhibition on a mouse hepatocellular carcinoma xenograft. These results suggest that mitochondria targeted PEG-Mn-BDA was able to simultaneously induce selective inhibition on cancer cells and a mouse carcinoma xenograft, label cancer cells with fluorescence and enhance MRI contrast. Therefore, PEG-Mn-BDA is a good candidate for cancer treatment and imaging.

Evaluation on the inhibition of pyrrol-2-yl ethanone derivatives to lactate dehydrogenase and anticancer activities.

Lactate dehydrogenase A (LDH-A) is a potentially important metabolic target for the inhibition of the highly activated glycolysis pathway in cancer cells. In order to develop bifunctional compounds as inhibitor of LDH-A and anticancer agents, two pyrrol-2-yl methanone (or ethanone) derivatives (PM1 and PM2) were synthesized and evaluated as inhibitors of LDH-A based on the enzyme assay and cell assay by spectroscopy analysis. Fluorescence and CD spectra results demonstrated that both the change of second structure of LDH-A and the affinity interaction for compounds to LDH-A gave great effect on the activity of LDH-A. In particular, low concentration of compounds (1µµ-25µµ) could change the level of pyruvate in cancer cells. Moreover, the in vitro assay results demonstrated that pyrrol-2-yl ethanone derivatives can inhibit the proliferation of cancer cells. Therefore, pyrrol-2-yl ethanone derivatives (PM2) can be both LDH-A inhibitor and anticancer agents.

A Mn(II) complex of boradiazaindacene (BODIPY) loaded graphene oxide as both LED light and H2O2 enhanced anticancer agent.

Cancer cells are more susceptible to H2O2 induced cell death than normal cells. H2O2-activatable and O2-evolving nanoparticles could be used as photodynamic therapy agents in hypoxic environments. In this report, a photo-active Mn(II) complex of boradiazaindacene derivatives (Mn1) was used as a dioxygen generator under irradiation with LED light in water. Moreover, the in vitro biological evaluation for Mn1 and its loaded graphene oxide (herein called Mn1@GO) on HepG-2 cells in normal and hypoxic conditions has been performed. In particular, Mn1@GO can react with H2O2 resulting active anticancer species, which show high inhibition on both HepG-2 cells and CoCl2-treated HepG-2 cells (hypoxic cancer cells). The mechanism of LED light enhanced anticancer activity for Mn1@GO on HepG-2 cells was discussed. Our results show that Mn(II) complexes of boradiazaindacene (BODIPY) derivatives loaded GO can be both LED light and H2O2-activated anticancer agents in hypoxic environments.

Mn(ii) silver-aptamer clusters for targeted MR imaging of tumors.

Hypoxia-inducible factor (HIF) highly expressed in most of the cancer cells. The Mn(ii)-aptamer based nanoclusters with 3D structures would be HIF-aptamer based targeted magnetic resonance imaging agents for cancer MRI diagnosis. Herein, a new class of contrast agent Mn(ii) silver-aptamer clusters (AdpaMn@DNA-Ag-DNAG1) were constructed based on the assembly of DNA-mediated Ag nanoclusters (DNA-AgNCs) with the Mn(ii) complex (AdpaMn) and DNAG1, the recognition sequence of GLUT-1. Then, the Mn(ii) silver-aptamer clusters (AdpaMn@DNA-Ag-DNAG1) are used as the MRI agents both in vitro and in vivo. The results show that the MRI signal is clearly presented in the tumor position. Consequently, the Mn(ii) silver-aptamer clusters can be used as a new class of contrast agents for targeted MR imaging of tumors.

Study on the interaction of Fe(III) complex of BODIPY appended di(picolyl)amine with water and HeLa cells.

The iron complex [(m-BDA)FeCl3] (Fe1) (m-BDA=8-[di(2-picolyl)amine-3-benzyl]-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene) was characterized by spectroscopic methods. The emission intensity of Fe1 is weaker than that of m-BDA due to the electrostatic interaction between the Fe(III) ion and m-BDA. However, the coordination of water with the central Fe(III) ion in Fe1 changed metal-ligand charge transfer, thus the quenched emission at 509 nm was recovered. Furthermore, Fe1 can catalyze water oxidation to generate dioxygen when irradiated by green LED light (10W). In particular, the Fe1 can enter into HepG-2 cells and show different inhibition rates in black and under irradiation. The anticancer activity of Fe1 was greatly enhanced under irradiation. Our results demonstrate that Fe(III) complexes of BODIPY can be developed as new kinds of photodynamic agents.

Spectroscopic study on the interaction of Aß42 with di(picolyl)amine derivatives and the toxicity to SH-S5Y5 cells.

In order to confirm the neurotoxicity of bifunctional chelators containing hydrophobic groups and metal chelating moiety, the interaction of di(picolyl)amine (dpa) derivatives toward Aß42 peptide was investigated. Fluorescence titration reveals that a hydrophobic chelator (such as BODIPY) shows high binding affinity to amyloid Aß42. Circular dichroism (CD) spectra confirm that the hydrophobic bifunctional chelator can decrease α-helix fraction and increase the ß-sheet fraction of amyloid Aß42. In particular, experimental results indicate that a bifunctional chelator can assemble with Cu(II)-Aß42 forming chelator-Cu(II)-Aß42 nanospheres, which are toxic to SH-S5Y5 cells. The hydrophobic interaction between the chelator and the amyloid peptide (Aß42) has great contribution to the formation of neurotoxic chelator-Cu(II)-Aß42 nanospheres. This work gives a general guide to the development of low cytotoxic inhibitors of Aß42 aggregation.