Novel Gemcitabine-Re(I) Bisquinolinyl Complex Combinations and Formulations With Liquid Crystalline Nanoparticles for Pancreatic Cancer Photodynamic Therapy.

With less than 10% of 5-year survival rate, pancreatic ductal adenocarcinoma (PDAC) is known to be one of the most lethal types of cancer. Current literature supports that gemcitabine is the first-line treatment of PDAC. However, poor cellular penetration of gemcitabine along with the acquired and intrinsic chemoresistance of tumor against it often reduced its efficacy and hence necessitates the administration of high gemcitabine dose during chemotherapy. Photodynamic therapy (PDT), a more selective and minimally invasive treatment, may be used synergistically with gemcitabine to reduce the doses utilized and dose-related side effects. This study reports the synergistic use of Re(I) bisquinolinyl complex, a transition metal complex photosensitizer with gemcitabine against PDAC. Re(I) bisquinolinyl complex was found to act synergistically with gemcitabine against PDAC in vitro at various ratios. With the aim to enhance cellular uptake and therapeutic efficiency, the Re(I) bisquinolinyl complex and gemcitabine were encapsulated into liquid crystalline nanoparticles (LCNPs) system. The formulations were found to produce homogeneous drug-loaded LCNPs (average size: 159-173 nm, zeta potential +1.06 to -10 mV). Around 70% of gemcitabine and 90% of the Re(I) bisquinolinyl complex were found to be entrapped efficiently in the formulated LCNPs. The release rate of gemcitabine or/and the Re(I) bisquinolinyl complex loaded into LCNPs was evaluated in vitro, and the hydrophilic gemcitabine was released at a faster rate than the lipophilic Re(I) complex. LCNPs loaded with gemcitabine and Re(I) bisquinolinyl complex in a 1:1 ratio illustrated the best anti-cancer activity among the LCNP formulations (IC50 of BxPC3: 0.15 µM; IC50 of SW 1990: 0.76 µM) through apoptosis. The current findings suggest the potential use of transition metal-based photosensitizer as an adjunctive agent for gemcitabine-based chemotherapy against PDAC and the importance of nano-formulation in such application.

Antimicrobial and antibiofilm activities of Cu(II) Schiff base complexes against methicillin-susceptible and resistant Staphylococcus aureus.

BACKGROUND: Methicillin-resistance S. aureus (MRSA) possesses the ability to resist multiple antibiotics and form biofilm. Currently, vancomycin remains the last drug of choice for treatment of MRSA infection. The emergence of vancomycin-resistant S. aureus (VRSA) has necessitated the development of new therapeutic agents against MRSA. In this study, the antimicrobial and antibiofilm activities of two copper-complexes derived from Schiff base (SBDs) were tested individually, and in combination with oxacillin (OXA) and vancomycin (VAN) against reference strains methicillin-susceptible and methicillin-resistant Staphylococcus aureus. The toxicity of the SBDs was also evaluated on a non-cancerous mammalian cell line. METHODS: The antimicrobial activity was tested against the planktonic S. aureus cells using the microdilution broth assay, while the antibiofilm activity were evaluated using the crystal violet and resazurin assays. The cytotoxicity of the SBDs was assessed on MRC5 (normal lung tissue), using the MTT assay. RESULTS: The individual SBDs showed significant reduction of biomass and metabolic activity in both S. aureus strains. Combinations of the SBDs with OXA and VAN were mainly additive against the planktonic cells and cells in the biofilm. Both the compounds showed moderate toxicity against the MRC5 cell line. The selectivity index suggested that the compounds were more cytotoxic to S. aureus than the normal cells. CONCLUSION: Both the SBD compounds demonstrated promising antimicrobial and antibiofilm activities and have the potential to be further developed as an antimicrobial agent against infections caused by MRSA.

Recent Emergence of Rhenium(I) Tricarbonyl Complexes as Photosensitisers for Cancer Therapy.

Photodynamic therapy (PDT) is emerging as a significant complementary or alternative approach for cancer treatment. PDT drugs act as photosensitisers, which upon using appropriate wavelength light and in the presence of molecular oxygen, can lead to cell death. Herein, we reviewed the general characteristics of the different generation of photosensitisers. We also outlined the emergence of rhenium (Re) and more specifically, Re(I) tricarbonyl complexes as a new generation of metal-based photosensitisers for photodynamic therapy that are of great interest in multidisciplinary research. The photophysical properties and structures of Re(I) complexes discussed in this review are summarised to determine basic features and similarities among the structures that are important for their phototoxic activity and future investigations. We further examined the in vitro and in vivo efficacies of the Re(I) complexes that have been synthesised for anticancer purposes. We also discussed Re(I) complexes in conjunction with the advancement of two-photon PDT, drug combination study, nanomedicine, and photothermal therapy to overcome the limitation of such complexes, which generally absorb short wavelengths.