Synthesis, aggregation and cellular investigations of porphyrin-cobaltacarborane conjugates

A new series of porphyrin-cobaltacarborane conjugates (1-5) that contain four to sixteen carborane clusters per porphyrin macrocycle, were prepared in excellent yields (90-97 %) by means of a ring-opening reaction of the zwitterionic cobaltacarborane [3,3'-Co(8-C(4)H(8)O(2-)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))]. The X-ray structure of one conjugate (3) is presented. The aggregation properties of these conjugates were investigated by using absorption and fluorescence spectrophotometry, and the stages of microcrystal formation were captured by using atomic force microscopy. All conjugates were found to aggregate in aqueous solutions, to form a broad dispersity of particle sizes. The cellular uptake, cytotoxicity, and preferential sites of subcellular localization of this series of conjugates were evaluated in human carcinoma HEp2 cells. The extent of conjugate cellular uptake depends on the number of cobaltacarborane units at the porphyrin periphery, their distribution, and the conjugate aggregation behavior. Conjugates 2 and 4, bearing either two adjacent or three 3,5-dicobaltacarboranephenyl groups, accumulated the most within HEp2 cells and are, therefore, the most promising boron neutron capture therapy agents. All conjugates showed very low dark- and photo-toxicity, probably due to their strong tendency for aggregation in aqueous solutions, and localized subcellularly within vesicles that correlated, to some extent, with the cell lysosomes.     

B12H11-containing guanidinium derivatives by reaction of carbodiimides with H3N-B12H11(1−). A new method for connecting boron clusters to organic compounds

The reaction of B₁₂H₁₁NH₃(1−) with carbodiimides can form guanidinium salts containing the boron cluster. Depending on the side chains of the carbodiimide, these derivatives of the B₁₂H₁₂(2−) cluster can be uncharged or can carry an overall positive or negative charge. This reaction allows the preparation of derivatives with aliphatic side chains, in contrast to the acylation reaction of and the formation of Schiff bases, both of which are successful only with aromatic acid chlorides or aromatic, respectively, α,β-unsaturated aldehydes. The acylation of with benzoyl chloride gives an N-protonated form of an imidoacid, carrying a single overall charge.     

Common Practices of Voice Therapists in the Evaluation of Patients

This study surveys voice therapists regarding common diagnostic practices in patients referred for therapy with the diagnosis of muscle tension dysphonia (broadly defined as the "hyperfunctional" component of the dysphonia). Through postings on the e-mail list of the ASHA special interest division on voice, speech pathologists with at least 3 years' experience in stroboscopy and acoustic instrumentation were invited to complete the survey. Results from 53 completed surveys demonstrated that voice quality and patient self-perception are the sole assessments performed by all therapists. Voice quality, observation of body posture and movement, and probing the patient's ability to alter voice production are each significantly more likely to be performed than the more objective stroboscopic, acoustic, aerodynamic, and EGG assessments. Further, the tasks of defining specific therapy session goals and helping the patient to achieve a particular target skill are considered best served by measures of vocal quality, observation of body position and movement, and judging the patient's ability to alter voice production. For definition of the overall therapy goal, stroboscopy and patient perception scales are added to all of the subjective assessment measures as being important. Acoustic data are considered most important for patient reinforcement and outcomes assessment. Implications of these findings are discussed, and topics for further exploration are identified.     

Phytochemical and pharmacological properties of essential oils from Cedrus species

Natural products frequently exert pharmacological activities. The present review gives an overview of the ethnobotany, phytochemistry and pharmacology of the Cedrus genus, e.g. cytotoxic, spasmolytic immunomodulatory, antiallergic, anti-inflammatory and analgesic activities. Cancer patients frequently seek remedies from traditional medicinal plants that are believed to exert less side effects than conventional therapy with synthetic drugs. A long-lasting goal of anti-cancer and anti-microbial therapy research is to find compounds with reduced side effects compared to currently approved drugs. In this respect, Cedrus species might be of interest. The essential oil isolated from Cedrus libani leaves may bear potential for drug development due to its high concentrations of germacrene D and β-caryophyllene. The essential oils from Cedrus species also show bioactivity against bacteria and viruses. More preclinical analyses (e.g. in vivo experiments) as well as clinical trials are required to evaluate the potential of essential oils from Cedrus species for drug development.     

荧光金属纳米簇的合成及其在生物医学中的应用研究进展

金属纳米簇作为一种新型的荧光纳米材料,展现出良好的生物相容性和优良的物化性质,近年来受到各个领域的关注,尤其在生物医学领域得到了广泛的应用。该文在介绍多种金属纳米簇的合成方法和光学性质的基础上,综述了金属纳米簇在生物传感、生物成像和肿瘤治疗等领域的应用研究进展,并对其面临的挑战和应用前景进行了展望。     

A Light‐Up Probe with Aggregation‐Induced Emission for Real‐Time Bio‐orthogonal Tumor Labeling and Image‐Guided Photodynamic Therapy

Bio‐orthogonal tumor labeling is more effective in delivering imaging agents or drugs to a tumor site than active targeting strategy owing to covalent ligation. However, to date, tumor‐specific imaging through bio‐orthogonal labeling largely relies on body clearance to differentiate target from the intrinsic probe signal owing to the lack of light‐up probes for in vivo bio‐orthogonal labeling. Now the first light‐up probe based on a fluorogen with aggregation‐induced emission for in vivo bio‐orthogonal fluorescence turn‐on tumor labeling is presented. The probe has low background fluorescence in aqueous media, showing negligible non‐specific interaction with normal tissues. Once it reacts with azide groups introduced to tumor cells through metabolic engineering, the probe fluorescence is lightened up very quickly, enabling rapid tumor‐specific imaging. The photosensitizing ability was also used to realize effective image‐guided photodynamic tumor therapy.     

In vitro and in vivo evaluation of improved EGFR targeting peptide-conjugated phthalocyanine photosensitizers for tumor photodynamic therapy

A serial of peptide-conjugated zinc phthalocyanines with finely tuned structure modification were prepared and one optimized conjugate showed improved targeting towards tumors and abolished inoculated tumors with only a single PDT treatment in a subcutaneous xenograft tumor model, making this approach a promising therapeutic agent for the treatment of cancer.     

Platelet‐Facilitated Photothermal Therapy of Head and Neck Squamous Cell Carcinoma

Here, we present a platelet‐facilitated photothermal tumor therapy (PLT‐PTT) strategy, in which PLTs act as carriers for targeted delivery of photothermal agents to tumor tissues and enhance the PTT effect. Gold nanorods (AuNRs) were first loaded into PLTs by electroporation and the resulting AuNR‐loaded PLTs (PLT‐AuNRs) inherited long blood circulation and cancer targeting characteristics from PLTs and good photothermal property from AuNRs. Using a gene‐knockout mouse model, we demonstrate that the administration of PLT‐AuNRs and localizing laser irradiation could effectively inhibit the growth of head and neck squamous cell carcinoma (HNSCC). In addition, we found that the PTT treatment augmented PLT‐AuNRs targeting to the tumor sites and in turn, improved the PTT effects in a feedback manner, demonstrating the unique self‐reinforcing characteristic of PLT‐PTT in cancer therapy.     

A Platinum(II) Complex of Heptamethine Cyanine for Photoenhanced Cytotoxicity and Cellular Imaging in Near‐IR Light

Controlled generation of cytotoxic agents with near‐IR light is a current focus of photoactivated cancer therapy, including that involving cytotoxic platinum species. A heptamethine cyanine scaffolded Pt^II complex, IR797‐Platin exhibits unprecedented Pt?O bond scission and enhancement in DNA platination in near‐IR light. This complex also displayed significant singlet oxygen quantum yield thereby qualifying as a near‐IR photodynamic therapeutic agent. The complex showed 30–60 fold enhancement of cytotoxicity in near‐IR light in various cancer cell lines. The cellular imaging properties were also leveraged to observe its significant co‐localization in cytoplasmic organelles. This is the first demonstration of a near‐IR light‐initiated therapy involving the cytotoxic effects of both active cisplatin and singlet oxygen.     

Meso-substituted porphyrin photosensitizers with enhanced near-infrared absorption: Synthesis,characterization and biological evaluation for photodynamic therapy

Porphyrin derivatives are widely explored and used in photodynamic therapy, for their marvelous therapeutic properties. In order to fill in the gaps of insufficient photosensitizers with near-infrared absorption, three porphyrin molecules, 5,10,15,20-tetrakis(3,4-bis(2-(-2-(2-hydroxyethoxy)ethoxy)ethoxy)benzyl)zinc porphyrin(P1), 5,15-bis(3,4-bis(2-(-2-(2-hydroxyethoxy)ethoxy)ethoxy)benzyl)-10,20-bis(2-(2-(2-(4-ethynylphenoxy)ethoxy)ethoxy)ethanol)zincporphyrin(P2),5,15-bis(3,4-bis(2-(-2-(2-hydroxyethoxy)ethoxy)ethoxy)benzyl)-10,20-N,N-dibutyl-4-ethynylaniline zinc porphyrin(P3), were designed and synthesized targeting for more efficient cancer treatment. Excellent photophysical properties were illustrated by UV–vis absorption and emission spectra with enhanced absorbance between 650 and 750?nm and fluorescence emission within 600–800?nm. Besides, with high ¹O₂ quantum yield, especially P2 (0.89), all porphyrins were further evaluated in vitro by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay against Hela cells and exhibited negligible dark toxicity and robust phototoxicity. Fluorescence confocal laser microscopy confirmed cellular uptake and diffusion of these porphyrins, therefore demonstrated their potential and promising applications in photodynamic therapy.