A selenium-based NIR-II photosensitizer for a highly effective and safe phototherapy plan.

High efficiency, stability, long emission wavelength (NIR-II), and good biocompatibility are crucial for photosensitizers in phototherapy. However, current Food and Drug Administration (FDA)-approved organic fluorophores exhibit poor chemical stability and photostability as well as short emission wavelength, limiting their clinical usage. To address this, we developed Se-IR1100, a novel organic photosensitizer with a photostable and thermostable benzobisthiadiazole (BBTD) backbone. By incorporating selenium as a heavy atom and constructing a D-A-D structure, Se-IR1100 exhibits a maximum fluorescence emission wavelength of 1100 nm. Compared with FDA-approved indocyanine green (ICG), DSPE-PEGylated Se-IR1100 nanoparticles exhibit prominent photostability and long-lasting photothermal effects. Upon 808 nm laser irradiation, Se-IR1100 NPs efficiently convert light energy into heat and reactive oxygen species (ROS), inducing cancer cell death in cellular studies and living organisms while maintaining biocompatibility. With salient photostability and a photothermal conversion rate of 55.37%, Se-IR1100 NPs hold promise as a superior photosensitizer for diagnostic and therapeutic agents in oncology. Overall, we have designed and optimized a multifunctional photosensitizer Se-IR1100 with good biocompatibility that performs NIR-II fluorescence imaging and phototherapy. This dual-strategy method may offer novel approaches for the development of multifunctional probes using dual-strategy or even multi-strategy methods in bioimaging, disease diagnosis, and therapy.

NIR-II bioimaging of small molecule fluorophores: From basic research to clinical applications.

Due to the low autofluorescence and deep-photo penetration, the second near-infrared region fluorescence imaging technology (NIR-II, 1000-2000 nm) has been widely utilized in basic scientific research and preclinical practice throughout the past decade. The most attractive candidates for clinical translation are organic NIR-II fluorophores with a small-molecule framework, owing to their low toxicity, high synthetic repeatability, and simplicity of chemical modification. In order to enhance the translation of small molecule applications in NIR-II bioimaging, NIR-II fluorescence imaging technology has evolved from its usage in cells to the diagnosis of diseases in large animals and even humans. Although several examples of NIR-II fluorescence imaging have been used in preclinical studies, there are still many challenges that need to be addressed before they can finally be used in clinical settings. In this paper, we reviewed the evolution of the chemical structures and photophysical properties of small-molecule fluorophores, with an emphasis on their biomedical applications ranging from small animals to humans. We also explored the potential of small-molecule fluorophores.

NIR-II Emissive Ru(II) Metallacycle Assisting Fluorescence Imaging and Cancer Therapy.

Despite the success of emissive Ruthenium (Ru) agents in biomedicine, problems such as the visible-light excitation/emission and single chemo- or phototherapy modality still hamper their applications in deep-tissue imaging and efficient cancer therapy. Herein, an second nearinfrared window (NIR-II) emissive Ru(II) metallacycle (Ru1000, λem  = 1000 nm) via coordination-driven self-assembly is reported, which holds remarkable deep-tissue imaging capability (≈6 mm) and satisfactory chemo-phototherapeutic performance. In vitro results indicate Ru1000 displays promising cellular uptake, good cancer-cell selectivity, attractive anti-metastasis properties, and remarkable anticancer activity against various cancer cells, including cisplatin-resistant A549 cells (IC50  = 3.4 × 10-6  m vs 92.8 × 10-6  m for cisplatin). The antitumor mechanism could be attributed to Ru1000-induced lysosomal membrane damage and mitochondrial-mediated apoptotic cell death. Furthermore, Ru1000 also allows the high-performance in vivo NIR-II fluorescence imaging-guided chemo-phototherapy against A549 tumors. This work may provide a paradigm for the development of long-wavelength emissive metallacycle-based agents for future biomedicine.

Rigidity Bridging Flexibility to Harmonize Three Excited-State Deactivation Pathways for NIR-II-Fluorescent-Imaging-Guided Phototherapy.

Small organic phototherapeutic molecules of the second near-infrared (NIR-II) window (1000-1700 nm) serve as promising candidates for theranostics. However, developing such versatile agents for fluorescence-guided photodynamic/photothermal therapy remains a demanding task stirred by competitive energy dissipation pathways, including radiative decay, internal conversion, and intersystem crossing. To the best of current knowledge, the current paradigm for addressing the issue has deliberately approached the optimum balance among three deactivation processes through offsetting from each other, possibly leading to a comprehensively compromised theranostic efficacy. Few reports aim to modulate the three deactivation pathways excluding sacrificing any one of them. Herein, a molecular design strategy to construct a phototherapeutic organic fluorophore CCNU-1060, armed with NIR-II luorescence-guided phototherapeutic properties, is rationally developed. With a flexible motor, tetraphenylethene, bridged to the rigidified coplanar core boron-azadipyrromethene, the desired CCNU-1060 is subsequently encapsulated into an amphiphilic matrix to form CCNU-1060 nanoparticles (NPs), which match or transcend its precursor NJ-1060 NPs in the three energy dissipation processes. CCNU-1060 NPs are utilized to realize high-spatial vessel imaging and effective NIR-II fluorescence-guided phototherapeutic tumor ablation. This study unlocks a viewpoint of molecular engineering that simultaneously regulates multiple energy dissipation pathways for the construction of versatile phototherapy agents.

Unprecedented toughening high-performance polyhexahydrotriazines constructed by incorporating point-face cation-π interactions in covalently crosslinked networks and the visual detection of tensile strength.

We described a new concept for the design of high-performance supramolecular thermosets by incorporating point-face cation-π interactions in covalently crosslinked networks. Our findings showed an unprecedented increase in tensile strength and extensibility at once, a previously unknown behavior for stiff high performance polymers.

Risk factors and clinical characteristics of tacrolimus-induced acute nephrotoxicity in children with nephrotic syndrome: a retrospective case-control study.

PURPOSE: Acute nephrotoxicity is a common adverse reaction of tacrolimus therapy; however, its risk factors in pediatric nephrotic syndrome (NS) remain to be evaluated. The objective of this study was to investigate the risk factors and characteristics of tacrolimus-induced acute nephrotoxicity in children with NS. METHODS: Past records of children with NS admitted to our hospital from 2014 to 2018 were reviewed. The incidence and characteristics of nephrotoxicity were analyzed. Multivariate logistic regression analysis was used to identify the risk factors of nephrotoxicity. A clinically applicable risk score was developed and validated. RESULTS: Tacrolimus-induced nephrotoxicity occurred in 25 of 129 patients, 13 patients were grade 1, and the renal function was recovered in 22 patients. Multivariate regression analysis showed that the maximum trough concentrations (C12h) of tacrolimus (OR, 1.48; 95% CI, 1.16 to 1.88; P < 0.001), huaiqihuang granules (OR, 0.095; 95% CI, 0.014 to 0.66; P = 0.017), and diarrhea (OR, 22.00; 95% CI, 1.58 to 306.92; P = 0.022) were independently associated with tacrolimus-induced nephrotoxicity. The maximum C12h were significantly higher in patients with nephrotoxicity (median 9.0 ng/ml) and the cut-off value for acute nephrotoxicity was 6.5 ng/ml. The area under the receiver operating characteristic curve was 0.821 for the proposed model based on the observations used to create the model and 0.817 obtained from k-fold cross-validation. CONCLUSIONS: High trough concentration of tacrolimus and diarrhea can potentiate the risk of tacrolimus-induced acute nephrotoxicity in children with NS, while huaiqihuang granules can protect this condition.

LiMII (IO3 )3 (MII =Zn and Cd): Two Promising Nonlinear Optical Crystals Derived from a Tunable Structure Model of α-LiIO3.

Excellent nonlinear optical materials simultaneously meet the requirements of large SHG response, phase-matching capability, wide transparency windows, considerable energy band-gap, good thermal stability and structure stability. Herein, two new promising nonlinear optical (NLO) crystals LiMII (IO3 )3 (MII =Zn and Cd) are rationally designed by the aliovalent substitution strategy from the commercialized α-LiIO3 with the perfect parallel alignment of IO3 groups. Compared with parent α-LiIO3 and related AI 2 MIV (IO3 )6 , the title compounds exhibit more stable covalent 3D structure, and overcome the racemic twinning problem of AI 2 MIV (IO3 )6 . More importantly, both compounds inherit NLO-favorable structure merits of α-LiIO3 and show larger SHG response (≈14× and ≈12×KDP), shorter absorption edge (294 and 297 nm) with wider energy band-gap (4.21 and 4.18 eV), good thermal stability (460 and 430 °C), phase-matching behaviors, wider optical transparency window and good structure stability, achieving an excellent balance of NLO properties.

KBi(IO3)3(OH) and NaBi(IO3)4: from the centrosymmetric chain to a noncentrosymmetric double layer.

Two new alkali-metal bismuth iodates KBi(IO3)3(OH) (1) and NaBi(IO3)4 (2) have been synthesized by a hydrothermal method via tuning of alkali-metal ions. Compound 1 crystallizes in the space group P1[combining macron] and features a [Bi(IO3)3(OH)]n chain with eight-membered Bi-O-I-O-Bi-O-I-O rings. The [Bi(IO3)3(OH)]n chain consists of paddlewheel-like dimeric Bi2(OH)2(IO3)4 units linked by IO3 pairs. Compound 2 in the polar space group Cc features a [Bi(IO3)4]- double layer with Bi4I4 eight-membered rings (8-MRs). NaBi(IO3)4 exhibits a strong second harmonic generation (SHG) response of ∼5.0 × KDP (KH2PO4) and a wide transmittance window (0.4-12 µm), and structure analyses and theoretical calculations reveal that polarization results mainly from the proper alignment of the IO3 groups. The calculated electronic structure based on the DFT method indicates that the BiOn and IO3 groups dominate their optical properties.

A Retrospective Analysis on 1330 Adverse Event Reports of Qingkailing in China: Further Perception of Its Risks and Rational Use.

Qingkailing (QKL) is a modern preparation exploited according to the traditional Chinese medicine theory. It becomes the second leading cause of adverse drug events (ADEs) in all traditional Chinese medicine injections. The safety evaluation and rational use of QKL are of special importance. This retrospective study used data from Adverse Drug Reaction Monitoring Center of Hubei Province in China from January 2012 to December 2014. ADE cases induced by QKL were collected and analyzed according to patients' demographics, characteristics of drugs involved, characteristics of ADEs, causality, and outcomes. A total of 1330 qualified ADEs were included. Most ADEs occurred within 30 min after administration and the 0-10 years old age group had the highest number of ADEs. The common ADEs included anaphylactic reaction, dyspnea and nausea. Serious reactions accounted for 5.19%. Combination with cephalosporin (74/146, 50.69%) caused more ADEs than other drugs did. Serious attention should be paid when QKL is used for children, and combination with cephalosporin should be avoided.

Front-side illuminated CdS/CdSe quantum dots co-sensitized solar cells based on TiO2 nanotube arrays.

We fabricated a front-side illuminated CdS/CdSe quantum dots co-sensitized solar cell based on TiO(2) nanotube arrays. The freestanding TiO(2) nanotube arrays were first detached from anodic oxidized Ti foils and then transferred to the fluorine-doped tin oxide to form photoanodes. An opaque Cu(2)S with high electrochemical activity was used as the counter electrode. A photovoltaic conversion efficiency as high as 3.01% under one sun illumination has been achieved after optimizing the deposition time of CdSe quantum dots and the length of the TiO(2) nanotube arrays. It is observed that the power conversion efficiency of quantum dots sensitized solar cells from the front-side illumination mode (3.01%) is much higher than that of the back-side illumination mode (1.32%) owing to the poor catalytic activity of Pt to polysulfide electrolytes and light absorption by the electrolytes for the latter.

[Enhanced thymidine kinase gene vector and its killing effect on nasopharyngeal carcinoma in vitro and in vivo].

OBJECTIVE: To construct a modified and enhanced thymidine kinase (TK) vector regulated by human telomerase catalytic subunit promoter (hTERT) promoter and cytomegalovirus (CMV) enhancer and its killing effect on nasopharyngeal carcinoma in vitro and in vivo and its safety in vivo. METHODS: The pGL3-basic, as basic vector template, was linked and constructed into TK vector regulated by hTERT promoter and CMV enhancer with mono-promoter vector as control. Enhanced TK expression was confirmed by fluorescent microscopy and real time fluorescent quantitative PCR. Telomerase activity was measured by stretch PCR. Tumour killing effects were examined by MTT and Boyden areola. The effects of enhanced TK on the invasiveness of tumor cell NPC 5-8F and the growth of xenograft implanted in nude mice were investigated. RESULTS: Compared with non-enhanced vector, TK expressed by the enhanced vector significantly increased in NPC 5-8F and MCF-7 cells, telomerase activity was positive in human in NPC 5-8F cells and breast cancer MCF-7 cells and negative in control human blood vessel endothelium ECV-304 cells. After ganciclovir(GCV) treatment, NPC 5-8F cell survival rate and invasiveness decreased and tumor progress of NPC xenograft implanted in nude mice was inhibited, without obvious toxicity effects on mouse liver and kidney. CONCLUSIONS: The enhanced TK vector regulated by hTERT promoter and CMV enhancer can obviously and specifically inhibit and kill nasopharyngeal carcinoma cells in culture and nasopharyngeal carcinoma xenograft in nude mice in vivo, without obviously toxic side effects on nude mice. The targeted and enhanced TK gene vector with high performance may be a new tumour targeted gene therapy strategy clinically to aim directly at most malignant tumours including nasopharyngeal carcinoma, with more extensive anti-cancer spectrum.

Targeted gene therapy of nasopharyngeal cancer in vitro and in vivo by enhanced thymidine kinase expression driven by human TERT promoter and CMV enhancer.

BACKGROUND/AIM: To explore the therapeutic effects of thymidine kinase (TK) expressed by enhanced vector pGL3-basic- hTERTp-TK-EGFP-CMV driven by human telomerase reverse transcriptase promoter (hTERTp) as well as cytomegalovirus immediate early promoter enhancer (CMV). MATERIALS/METHODS: Enhanced TK-EGFP expression was confirmed by fluorescent microscopy, real time PCR and telomerase activity. Its effects were examined by survival of tumor cells NPC 5-8F and MCF-7, index of xenograft implanted in nude mice and histology. RESULTS: Compared with non-enhanced vector pGL3-basic-TK-hTERTp-EGFP, TK expressed by the enhanced vector significantly decreased NPC 5-8F and MCF-7 cell survival rates after ganciclovir (GCV) treatment (p < 0.001) and tumor progress in nude mice with NPC xenograft and treated with GCV, without obvious toxicity to mouse liver and kidney. CONCLUSION: The enhanced TK expression vector driven by hTERTp with CMV enhancer has brighter clinical potentials in nasopharyngeal carcinoma therapy than the non-enhanced vector.

[Study on the relationship between TK gene regulated by enhanced suicide gene vector and telomerase activity in nasopharyngeal carcinoma cells].

OBJECTIVE: To explore the relationship between TK gene expression regulated by enhanced suicide gene vector and telomerase activity in nasopharyngeal carcinoma cells. METHOD: The reformed reconstructed enhanced vector, pGL3-basic-EGFP-TK-hTRETp-CMV enhancer, and hTERT mono-promoter vector, pGL3-basic-EGFP-TK-hTRETp(as controls), were transfected into telomerase(+) nasopharyngeal carcinoma 5-8F cell lines, telomerase(+) human breast cancer MCF-7 cell lines and telomerase(-) normal vascular endothelium cell lines respectively. TK gene green fluorescent protein was observed by fluorescence microscope. The expression of TK gene mRNA was measured by the real-time fluorescent quantified PCR and the telomerase activity was determined by the method of TRAP argentation in malignant tumour cells pre- and post-transfected by enhanced vector. Meanwhile the relationship between TK and telomerase was analyzed. RESULT: (1) A strong TK gene fluorescent show and TK mRNA expression were displayed after the enhanced suicide gene vector was transfected into nasopharyngeal carcinoma 5-8F cell lines and human breast cancer MCF-7 cell line, which were more stronger than those of mono-promoter group, pGL3-basic-EGFP-TK-hTRETp, and ECV cells transfected by enhanced suicide gene vector. Meanwhile,real-time fluorescent quantified PCR showed that the A value of enhanced vector group was higher than that of controls. (2) Telomerase activity after transfection of enhanced vector and GCV was lower than those before by the method of TRAP argentation in nasopharyngeal carcinoma cell lines,but no change in normal control cells after transfection of enhanced vector and GCV. (3) After adding GCV, the obvious inhibitory effect of tumour cells growth induced by pGL3-basic-EGFP-TK-hTRETp-CMV enhancer were observed in nasopharyngeal carcinoma 5-8F cell lines and human breast cancer MCF-7 cell line, which was higher than those of mono-promoter, pGL3-basic-EGFP-TK-hTRETp, pGL3-basic-EGFP3 and blank controls, but without inhibitory effect in ECV cells transfected by enhanced vector. CONCLUSION: TK gene expression is regulated by hTERT promoter and CMV enhancer, and then the telomerase activity is reduced and the cancer cells are specifically killed. But it is unclear how the telomerase are down-regulated by TK gene.