Photoresponsive Nanoarchitectonics Based on Copper-Porphyrins for Near-Infrared-Enhanced Bacterial Treatment.

Antibiotic resistance is one of the biggest challenges that causes incurable diseases and endangers public health. Metal-porphyrin-modified nanoarchitectonics can enhance the bacterial affinity and destruction of cell walls. Herein, a new photoresponsive nanoarchitectonics (BPGa@COF-Cu) was synthesized by doping Ga(III) on the surface of black phosphorus (BP) and subsequently loaded into a Cu(II)-based covalent-organic framework (COF-Cu). The COF-Cu was induced by the coupling reaction of terephthalic chloride with amino-substituted porphyrin derivatives (THPP), followed by the coordination of the Cu(II) ion. The material BPGa@COF-Cu is a nanoball, and the mean radius is ca. 250 nm. The photochemical properties of BPGa@COF-Cu show that it efficiently catalyzes H2O2 into ·OH. BPGa@COF-Cu can also produce both singlet oxygen and heat upon 808 nm irradiation. Further, BPGa@COF-Cu was employed to inhibit bacteria, and the results showed that it can destroy the membrane of bacteria. The MIC (minimal inhibition concentration) of BPGa@COF-Cu against E. coli was 1 µg/mL. All the data suggest that BPGa@COF-Cu is a multiple nanoarchitectonics for bacterial treatment.

Europium- and Black Phosphorus-Functionalized Porphyrin as an l-Arginine Sensor and l-Arginine-Activated PDT/PTT Agent for Bacterial Treatment.

The attenuation of bacterial metabolism provides an adjunct to the treatment of bacterial infections. To develop a bacterial eradication agent, a bioactivatable material (BP@Eu-TCPP) was designed and synthesized by coordination and reduction of europium(III) with thin-layer black phosphorus (BP) and tetrakis (4-carboxyphenyl) porphyrin (TCPP). The existence of the P-Eu bond and Eu2+ 3d5/2 in X-ray photoelectron spectroscopy confirmed the successful synthesis of BP@Eu-TCPP. This material showed high fluorescence sensitivity to l-Arginine (l-Arg) and the main binding ratio of BP@Eu-TCPP to l-Arg was ca. 1:2 or 1:3, with the limit of detection of 4.0 µM. The material also showed good photothermal properties and stability, with a photothermal conversion efficiency of 37.3%. Although metal coordination has blocked the generation of 1O2, the addition of l-Arg to BP@Eu-TCPP can restore 1O2 generation upon red light-emitting diode (LED) light irradiation due to the formation of water-soluble Arg-TCPP species. Additionally, BP@Eu-TCPP was enabled to change the bacterial membrane and interfered with the bacterial iron absorption that effectively contributes to bacterial eradication. Such BP@Eu-TCPP is promised to be a novel material for the detection of l-Arg and l-Arg-activated photodynamic therapy.

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.

Gold as a coordinator of an imidazole conjugated dye of BODIPY derivatives for the identification of simple mercaptans.

Rapid detection of mercaptans in materials and the environment is of great help to material analysis and pollutant monitoring. Gold (Au) shows a high affinity to mercaptans. The coordination and steric effect of mercaptans to Au may be used for the development of new fluorescent sensors. It is possible to distinguish simple mercaptans (such as, HS-, thioglycolic acid) from glutathione (GSH) using Au as a coordinator of dye. Herein, a water-soluble fluorescent sensor of an imidazole conjugated 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivative (BIM) was characterized by spectroscopic methods. BIM showed a large Stokes shift and high affinity to metals. Especially, Au-combined BIM produced a new complex BIMAu showing improved fluorescence emission, which can be quenched by thioglycolic acid and sodium hydrosulfide, but less affected by GSH. The detection limit of thioglycolic acid was 0.014 µM. Both NaSH and thioglycolic acid coordinated with BIMAu, while GSH took Au3+ away from BIMAu. These results indicate that the gold coordination competition between imidazole-substituted dyes and mercaptans is a good method for the development of new fluorescence chemosensors.

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.

A Fluorescent Visual Proton Donor and Photoacid Sterilant Based on Sulfonate-conjugated BODIPY.

Increasing acidity is an effective method for bacterial inactivation by inhibiting the synthesis of intracellular proteins at low pH. Photo-driven proton release probe can be used for the measurement of proton in hydrophobic condition. To develop fluorescent proton donor, two boron dipyrromethene derivatives (BDP-S and BDP-S2) were characterized by spectroscopic methods. Irradiation of BDP-S by white LED light resulted in efficient generation of acidic species with changes of fluorescence emission. The linear relationship between the pH value and the fluorescence intensity of BDP-S was obtained, indicating that BDP-S is a fluorescent visual proton donor. Light-induced antibacterial results indicate that BDP-S can significantly inhibit the growth of E. coli. The results prove that BDP-S is a very promising photoacid sterilant.

Functional BOD-Ad-Cmyc@BSA complex nanosensor for Cu(II) and the detection of live E. coli.

Escherichia coli (E. coli) is abundantly present in nature. It is generally harmless to humans but some strains have been deemed very dangerous. Therefore, as an indicator of hygienic testing, the detection of E. coli is essential. In this work, a fluorescent assembly was synthesized and characterized by spectroscopic methods. It was found that the amantadine (Ad) conjugated dye (BOD-Ad) intercalated into Cmyc G4 (aptamer) forming a non-emission assembly (BOD-Ad-Cmyc), which could be lighted-up by BSA due to the formation of fluorescence nanoparticle BOD-Ad-Cmyc@BSA. Further, BOD-Ad-Cmyc@BSA can selectively bind Cu2+ forming non-emission species BOD-Ad-Cmyc@BSA-Cu2+. E. coli can turn-on the emission of BOD-Ad-Cmyc@BSA-Cu2+ system due to the copper accumulation or reduction by E. coli. Therefore, a fluorescence method for the determination of E. coli was built. The detection limit of BOD-Ad-Cmyc@BSA-Cu2+ of E. coli is 6.3 CFU/mL. Thus, this BOD-Ad-Cmyc@BSA-Cu2+ fluorescent assembly can be used for the detection of live E. coli in the environment.

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.

A Nano-BODIPY Encapsulated Zeolitic Imidazolate Framework As Photoresponsive Integrating Antibacterial Agent.

Drug-resistant bacteria challenge the antimicrobial agents and antibacterial strategy. To develop environmental friendly smart technology for treating pathogens, we report a kind of photoactivated nano-BODIPY (BCNBA@ZIF). First BODIPY compound (BC) was synthesized by coupling phenethyl caffeate (CAPE) with brominated BODIPY through B-O bonds. Next, BC was encapsulated in ZIF-8 together with 2-nitrobenzaldehyde (o-NBA) to form photoactivated BCNBA@ZIF nanoparticles. TEM confirm the structural change of BCNBA@ZIF after illumination. BCNBA@ZIF is less toxic to cells without illumination. Under illumination of blue LED light, the BCNBA@ZIF worked as a photoacid generator initiating the damage of ZIF shell with the release of BC, metal ions, and the production of singlet oxygen for achieving multifunctional antibacterial uses. Therefore, BCNBA@ZIF is a kind of photodriven smart "Domino" agent for bacterial inhibition.

Determination of melamine and melamine-Cu(II) complexes in milk using a DNA-Ag hydrocolloid as the sensor.

Simple and sensitive methods are required for the detection of melamine since melamine is harmful to human health. To detect the content of melamine and metal-melamine species in milk products, a new luminescent DNA silver hydrocolloid (AgNC53) was synthesized using a modified C3A-rich aptamer as the template. The emission of AgNC53 at 617 nm is sensitive to both melamine-Cu(II) and melamine, while almost no response to the free Cu(II) ion was detected. Moreover, AgNC53 is used to detect precisely the content of melamine in milk with a detection limit as low as 2.7 × 10-8 M. Thus, the AgNC53-based fluorescence method is a "label-free" fluorescence technology that can be used for the determination of melamine or the melamine-Cu(II) complex in milk products.

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.

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.

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.

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.