Publications by authors named "Sherri McFarland"
Article Synopsis
- Researchers developed and studied five new iridium(III) complexes with thienyl groups to improve their performance in photodynamic therapy for cancer.
- They found that the number of thienyl units affected the complexes' light absorption and emission properties, shifting them to longer wavelengths, which is beneficial for therapy.
- In tests against melanoma and breast cancer cell lines, one complex showed significant photocytotoxicity when activated by visible light, remaining effective even under low-oxygen (hypoxic) conditions.
Article Synopsis
- Cetuximab (Cet)-IRDye800CW is an antibody-IRDye800CW conjugate that shows promise for identifying tumor margins during fluorescence-guided surgery and is being explored for post-surgery treatment of residual cancer cells using photodynamic therapy (PDT).
- The study highlights that increasing the number of dye molecules attached to the antibody from 2 to 11 enhances the effectiveness of Cet-IRDye800CW, enabling it to produce reactive species that can harm cancer cells, inducing approximately 90% phototoxicity in FaDu head and neck cancer cells.
- Antibody-targeted PDT with the higher dye payload offers improved cancer cell specificity and reduced toxicity in non-cancerous
A series of Ru(II) complexes incorporating two 4,4'-bis(trifluoromethyl)-2,2'-bipyridine (4,4'-btfmb) coligands and thienyl-appended imidazo[4,5-][1,10]phenanthroline (IP-T) ligands was characterized and assessed for phototherapy effects toward cancer cells. The [Ru(4,4'-btfmb)(IP-T)] scaffold has greater overall redox activity compared to Ru(II) polypyridyl complexes such as [Ru(bpy)]. - have additional oxidations due to the T group and additional reductions due to the 4,4'-btfmb ligands.
View Article and Find Full Text PDFRu(II) polypyridyl complexes have gained widespread attention as photosensitizers for photodynamic therapy (PDT). Herein, we systematically investigate a series of the type [Ru(phen)(IP-T)], featuring 1,10-phenanthroline (phen) coligands and imidazo[4,5-][1,10]phenanthroline ligands tethered to 0-4 thiophene rings (IP-T). The complexes were characterized and investigated for their electrochemical, spectroscopic, and (photo)biological properties.
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- Traditional Photodynamic Therapy (PDT) is limited to treating surface-level tumors due to low light penetration, prompting the exploration of radiation-activated PDT (radioPDT) which uses X-rays and nanoparticles for deeper tumor therapy.
- The study introduced a new type of pegylated poly-lactic-co-glycolic (PEG-PLGA) nanoparticles loaded with a highly efficient ruthenium-based photosensitizer, showing promising characteristics such as a small size and high loading efficiency.
- Results indicated that Ru/radioPDT only displays minimal toxicity until activated by X-rays, leading to greater cancer cell destruction compared to another radioPDT method, while also demonstrating a higher output of singlet oxygen, which is essential for
Article Synopsis
- Researchers investigated protic ruthenium complexes with dihydroxybipyridine (dhbp) ligands and spectator ligands (like bpy and phen) to evaluate their effectiveness against cancer cells and their luminescent properties.
- The study focuses on 16 complexes derived from two protonation states (acidic and deprotonated), including new complexes that were synthesized and characterized through spectroscopy and X-ray crystallography.
- Key findings show that certain complexes can be activated by light to exhibit photocytotoxicity, with specific complex characteristics such as longer luminescent lifetimes correlating with improved effectiveness against cancer cells.
Article Synopsis
- This study uses TLD1433, a Ru-based photodynamic therapy agent being tested in human trials, to create protocols for understanding how photosensitizers (PSs) behave in living cancer cells.
- It addresses the lack of knowledge about the excited-state dynamics of PSs in real biological settings and aims to analyze the light-triggered processes crucial for effective phototherapy.
- The research also applies the findings to a similar compound, TLD1633, which helps standardize methods for studying the behavior of phototoxic substances in complex biological environments.
Article Synopsis
- * Many research studies focus on varying one or two ligands on a common scaffold to understand how these changes affect the performance of Ru(II)-based PSs in PDT, but comparative studies with existing PSs have been limited.
- * A systematic review of Ru(II) PS studies since 2005 has been conducted, identifying their photophysical and light treatment data, which allows for quantifying their efficacy using the Photodynamic Threshold Model; results indicate a significant variation in the
Osmium (Os) based photosensitizers (PSs) are a unique class of nontetrapyrrolic metal-containing PSs that absorb red light. We recently reported a highly potent Os(II) PS, rac-[Os(phen) (IP-4T)](Cl) , referred to as ML18J03 herein, with light EC values as low as 20 pm. ML18J03 also exhibits low dark toxicity and submicromolar light EC values in hypoxia in some cell lines.
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- Osmium-based photosensitizers like [Os(phen)(IP-4T)](Cl) (ML18J03) are effective for photodynamic therapy (PDT) in deeper tissues but have low luminescence quantum yield, limiting imaging potential.
- Formulating ML18J03 into 10.2 nm DSPE-mPEG micelles (Mic-ML18J03) significantly boosts its luminescence yield by 100 times and enhances detection in tumors.
- The micellar formulation improves tumor selectivity and stability while also increasing the production of reactive species needed for effective PDT, showing promise for better imaging and treatment outcomes.
Article Synopsis
- Recent research has focused on octahedral complexes of Ru(II) and Os(II) with bidentate polypyridyl ligands, highlighting their potential in cancer treatment and their existence as enantiomers.
- The study successfully adapted Cyclofructan-6 (CF6) with (R)-naphthyl ethyl (RN) groups for SFC, achieving the first chiral separation of 23 different ionic complexes, revealing unique interactions and enantioselectivity influenced by the
Article Synopsis
- Desmoplasia, prevalent in pancreatic ductal adenocarcinoma (PDAC), creates barriers to treatment and contributes to a low 5-year survival rate of only 3%.
- The study introduces targeted photoactivable multi-inhibitor liposomes (TPMILs) that effectively combine photodynamic therapy and chemotherapy to combat PDAC while also reducing desmoplasia.
- TPMILs show a 90% reduction in tumor growth and significantly improve survival rates, making them a promising approach for patients with this aggressive cancer.
Article Synopsis
- Ru(II) complexes are being studied for their ability to produce cytotoxic effects in both oxygen-rich (normoxia) and oxygen-poor (hypoxia) environments, making them promising candidates for photochemotherapy (PCT).
- The research focuses on how two different excited state pathways influence the effectiveness of these complexes using specific Ru(dmp)(IP-T) structures, which transition from metal-centered (MC) states to ligand-based (ILCT) states.
- Findings show that certain complexes exhibit significant phototoxicity towards cancer cells in both normoxia and hypoxia, underscoring their potential as effective photosensitizers for cancer treatment, despite limitations in maximizing excited-state deactivation.
A family of complexes of the type [Ru(tpbn)(IP-R)(4-pic)]Cl (tbpn=2,2'-(4-(-butyl)pyridine-2,6-diyl)bis(1,8-napthyridine); 4-pic=4-picoline; IP-R=imidazo[4,5-][1,10]phenanthroline attached to an aromatic group R for - and H for ) were prepared as near-infrared (NIR) absorbing coordination complexes to test whether triplet intraligand excited states (IL) of higher energy than the lowest-lying triplet metal-to-ligand charge transfer excited states (MLCT) could effectively generate cytotoxic singlet oxygen (O) and elicit in vitro photodynamic therapy (PDT) effects. Aromatic groups ranged from benzene to anthracene, with corresponding triplet state energies that were all significantly higher (approximately 3.7-1.
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- * A study was conducted on TLD1433 and its derivative TLD1633 to understand their excited-state properties using biologically relevant solvents, focusing on interactions with biological macromolecules like DNA.
- * Findings indicate that binding to DNA increases the lifetime of the lowest-energy excited state, which is crucial for generating reactive oxygen species and causing cancer cell damage, highlighting the importance of studying these compounds' dynamics in biological contexts.
Article Synopsis
- Cancer therapies that trigger T cell responses are increasingly preferred over traditional treatments, particularly through a process called immunogenic cell death (ICD), which enhances the immune system's ability to recognize and attack tumors.
- Recent research has focused on developing novel photodynamic therapy (PDT) compounds, specifically two ruthenium-based compounds, ML19B01 and ML19B02, which can be activated by near infrared light to not only kill cancer cells but also stimulate immune responses.
- The study found that these PDT treatments led to the expression of key proteins associated with ICD, facilitating the activation of immune cells and resulting in anti-tumor immunity in mouse models against melanoma, demonstrating their potential for effective cancer immunotherapy.
Article Synopsis
- Photodynamic inactivation (PDI) is a technique that uses a photosensitizer, like the botanical extract PhytoQuin, along with light and oxygen to generate reactive oxygen species (ROS) that can inactivate microorganisms, including viruses.
- Research has shown that photoactivated PhytoQuin has antiviral effects against human coronaviruses, specifically HCoV-229E and HCoV-OC43, inhibiting their replication in cultured cells in a light-dependent manner.
- The study also found that PDI damages the viral integrity of coronaviruses, allowing for the breakdown of their RNA, and identified emodin, a component of PhytoQuin, as being critical to its antiviral activity.
Tumor hypoxia renders treatments ineffective that are directly (e.g., radiotherapy and photodynamic therapy) or indirectly (e.
View Article and Find Full Text PDFWe report new ruthenium complexes bearing the lipophilic bathophenanthroline (BPhen) ligand and dihydroxybipyridine (dhbp) ligands which differ in the placement of the OH groups ([(BPhen) Ru(n,n'-dhbp)]Cl with n = 6 and 4 in 1 and 2 , respectively). Full characterization data are reported for 1 and 2 and single crystal X-ray diffraction for 1 . Both 1 and 2 are diprotic acids.
View Article and Find Full Text PDFWe explore the photophysical properties of a family of Ru(II) complexes, , designed as photosensitizers (PSs) for photodynamic therapy (PDT). The complexes incorporate a 1-imidazo[4,5-][1,10]-phenanthroline (ip) ligand appended to one or more thiophene rings. One of the complexes studied herein, (known as TLD1433), is currently in phase II human clinical trials for treating bladder cancer by PDT.
View Article and Find Full Text PDFUnlabelled: TLD1433 is the first Ru(II) complex to be tested as a photodynamic therapy agent in a clinical trial. In this contribution we study TLD1433 in the context of structurally-related Ru(II)-imidozo[4,5-f][1,10]phenanthroline (ip) complexes appended with thiophene rings to decipher the unique photophysical properties which are associated with increasing oligothiophene chain length. Substitution of the ip ligand with ter- or quaterthiophene changes the nature of the long-lived triplet state from metal-to-ligand charge-transfer to ππ* character.
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- * A promising Ru(II) metal-organic dyad called TLD1433 has shown potential as a photodynamic therapy (PDT) agent for certain cancers, featuring a unique structure with an oligothiophene chain and an imidazophenanthroline ligand.
- * Researchers successfully synthesized and separated the enantiomers of five chiral Ru(II) and Os(II) PDT agents for the first time, using preparative liquid chromatography to produce enough material for absolute configuration analysis via vibrational circular dichro
Article Synopsis
- Alzheimer’s disease is a neurodegenerative disorder marked by brain damage and the accumulation of amyloid beta (Aβ) peptides, which contributes to its progression.
- This study examines how activating specific Ru(ii) polypyridyl complexes impacts Aβ peptide aggregation and promotes the formation of large amorphous aggregates instead of more toxic oligomers.
- The findings suggest that the presence of an extended phenanthroline ligand in these complexes enhances binding to Aβ and alters the aggregation dynamics, potentially providing insights into therapeutic strategies for AD.
Article Synopsis
- Over the last 20 years, photodynamic therapy (PDT) has shown potential not just as a local cancer treatment, but also for triggering a systemic immune response that helps prevent tumor recurrence, particularly in aggressive cancers like melanoma.
- Researchers have developed nine new near-infrared (NIR) photosensitizers (PSs) based on a specific chemical structure that demonstrate strong effectiveness against melanoma cells, achieving low concentrations for significant phototoxic effects with NIR light.
- When tested in mice, PDT treatment with one of the PSs activated a pro-inflammatory response and induced immunogenic cell death, resulting in substantial protection from tumor growth and improved survival rates after vaccination and subsequent tumor challenges.