A P-61 Black Widow Inspired Palladium Biladiene Complex for Efficient Sensitization of Singlet Oxygen Using Visible Light

Photodynamic therapy (PDT) is a promising treatment option that ablates cancerous cells and tumors via photoinduced sensitization of singlet oxygen. Over the last few decades, much work has been devoted to the development of new photochemotherapeutic agents for PDT. A wide variety of macrocyclic tetrapyrrole based photosensitizers have been designed, synthesized and characterized as PDT agents. Many of these complexes have a variety of issues that pose a barrier to their use in humans, including biocompatibility, inherent toxicity, and synthetic hurdles. We have developed a non-traditional, non-cyclic, and non-aromatic tetrapyrrole ligand scaffold, called the biladiene (DMBil1), as an alternative to these traditional photosensitizer complexes. Upon insertion of a heavy atom such as Pd2+ center, Pd[DMBil1] generates singlet oxygen in substantial yields (ΦΔ = 0.54, λexc = 500 nm) when irradiated with visible light. To extend the absorption profile for Pd[DMBil1] deeper into the phototherapeutic window, the tetrapyrrole was conjugated with alkynyl phenyl groups at the 2- and 18-positions (Pd[DMBil2-PE]) resulting in a significant redshift while also increasing singlet oxygen generation (ΦΔ = 0.59, 600 nm). To further modify the dialkynyl-biladiene scaffold, we conjugated a 1,8-diethynylanthracene with to the Pd[DMBil1] tetrapyrrole in order to further extend the compound’s π-conjugation in a cyclic loop that spans the entire tetrapyrrole unit. This new compound (Pd[DMBil2-P61]) is structurally reminiscent of the P61 Black Widow aircraft and absorbs light into the phototherapeutic window (600–900 nm). In addition to detailing the solid-state structure and steady-state spectroscopic properties for this new biladiene, photochemical sensitization studies demonstrated that Pd[DMBil2-P61] can sensitize the formation of 1O2 with quantum yields of ΦΔ = 0.84 upon irradiation with light λ = 600 nm. These results distinguish the Pd[DMBil2-P61] platform as the most efficient biladiene-based singlet oxygen photosensitizer developed to date. When taken together, the improved absorption in the phototherapeutic window and high singlet oxygen sensitization efficiency of Pd[DMBil2-P61] mark this compound as a promising candidate for future study as an agent of photodynamic cancer therapy.

Novel Multifunctional NIR-II Aggregation-Induced Emission Nanoparticles Assisted Intraoperative Identification and Elimination of Residual Tumor

Incomplete tumor resection is the direct cause of the tumor recurrence and metastasis after surgery. Intraoperative accurate detection and elimination of microscopic residual cancer improve surgery outcomes. In this study, a powerful D1-π-A-D2-R type phototheranostic based on aggregation-induced emission (AIE)-active the second near-infrared window (NIR-II) fluorophore is designed and constructed. The prepared theranostic agent, A1 nanoparticles (NPs), simultaneously shows high absolute quantum yield (1.23%), excellent photothermal conversion efficiency (55.3%), high molar absorption coefficient and moderate singlet oxygen generation performance. In vivo experiments indicate that NIR-II fluorescence imaging of A1 NPs precisely detect microscopic residual tumor (2 mm in diameter) in the tumor bed and metastatic lymph nodes. More notably, a novel integrated strategy that achieves complete tumor eradication (no local recurrence and metastasis after surgery) is proposed. In summary, A1 NPs possess superior imaging and treatment performance, and can detect and eliminate residual tumor lesions intraoperatively. This work provides a promising technique for future clinical applications achieving improved surgical outcomes.

Benzannulation of the Ditopic Ligand to Afford Mononuclear and Dinuclear Ir(III) complexes with intense phosphorescence. Application in Singlet Oxygen Generation and Bioimaging.

Annealing of additional aromatic pi-system to the ligand is an effective method of influencing the luminescence of metal complexes. In this contribution we show the effect of benzannulation of the...

The improvement of biocompatibility by incorporating porphyrins into carbon dots with photodynamic effects and pH sensitivities

Photodynamic therapy (PDT) is a promising new treatment for cancer; however, the hydrophobic interactions and poor solubility in water of photosensitizers limit the use in clinic. Nanoparticles especially carbon dots have attracted the attention of the world’s scientists because of their unique properties such as good solubility and biocompatibility. In this paper, we integrated carbon dots with different porphyrins to improve the properties of porphyrins and evaluated their efficacy as PDT drugs. The spectroscopic characteristics of porphyrins nano-conjugates were studied. Singlet oxygen generation rate and the light- and dark-induced toxicity of the conjugates were studied. Our results showed that the covalent interaction between CDs and porphyrins has improved the biocompatibility. The synthesized conjugates also inherit the pH sensitivity of the carbon dots, while the conjugation also decreases the hemolysis ratio making them a promising candidate for PDT. The incorporation of carbon dots into porphyrins improved their biocompatibility by reducing toxicity.

Design and In Vivo Evaluation of a Novel Transdermal Hydrogen/Oxygen-Generating Patch

Hydrogen/oxygen-generating biomaterials, a new trend in regenerative medicine, generate and supply hydrogen/oxygen to increase the local levels of hydrogen/oxygen to support tissue healing and regeneration. In this study, we carefully defined a strategic plan to develop a gas-permeable layer suitable for use in sanitary products that is capable of supplying hydrogen or oxygen in situ using calcium hydroxides as chemical oxygen sources. In vitro physicochemical evaluations of hydrogen- and oxygen-generation efficiency were performed to determine the amount of hydrogen and oxygen produced. An in vivo permeation study was conducted to assess biological parameters, including blood oxygen (O2) and hydrogen (H+) levels. The stress hormone corticosterone and inflammation marker interleukin 6 (IL-6) were also quantified. The hydrogen/oxygen-generating patch (HOGP) continuously generated H+ or O2 for up to 12 h after activation by water. An in vivo evaluation showed blood H+ peaked at 2 h after application of the HOGP and then progressively decreased until the end of study (24 h), whereas oxygen content (O2(ct)) and oxygen saturation (SO2(SAT)) continuously increased up to 6 h. Hematological and electrolyte parameters did not significantly change compared to baseline. Wearing the stretch fabric used to secure the patch did not significantly increase serum corticosterone or interleukin 6 (IL-6) in the animals. This novel design of a hydrogen/oxygen-generating biomaterial for supplying topical H+/O2 may hold potential for increasing in situ or circulating H+/O2 levels to improve healthcare outcomes.

Chlorin e6-Biotin Conjugates for Tumor-Targeting Photodynamic Therapy

To improve the tumor-targeting efficacy of photodynamic therapy, biotin was conjugated with chlorin e6 to develop a new tumor-targeting photosensitizer, Ce6-biotin. The Ce6-biotin had good water solubility and low aggregation. The singlet-oxygen generation rate of Ce6-biotin was slightly increased compared to Ce6. Flow cytometry and confocal laser scanning microscopy results confirmed Ce6-biotin had higher binding affinity toward biotin-receptor-positive HeLa human cervical carcinoma cells than its precursor, Ce6. Due to the BR-targeting ability of Ce6-biotin, it exhibited stronger cytotoxicity to HeLa cells upon laser irradiation. The IC50 against HeLa cells of Ce6-biotin and Ce6 were 1.28 µM and 2.31 µM, respectively. Furthermore, both Ce6-biotin and Ce6 showed minimal dark toxicity. The selectively enhanced therapeutic efficacy and low dark toxicity suggest that Ce6-biotin is a promising PS for BR-positive-tumor-targeting photodynamic therapy.