Theralase Technologies Inc. V.TLT

RE:New Paper from Dr. McFarland

[ScienceFirst]

Years of work before it gets to bedside.  But if it falls under our patent (this is an Os(II) molecule but is there subtilities that would not make it fall under it, this has to be verified), it could be part of the IP portfolio that could then be moved under the Theralase Anti-Cancer Therapy Research Centre that would have to bring it closer to clinical trials and bedside.  

ML stands for McFarland Laboratory.  

3. Results and Discussion

We have previously reported that the unformulated, free ML18J03 used in this study has EC50 values ranging from 7 × 10−4 μM to 0.0434 μM in SK-MEL-28 melanoma cells, following broadband visible light excitation, with considerable inter-assay variability due to its propensity to aggregate [10]. The liposomal and micellar formulations of ML18J03 from our previous study have EC50 values of 98.1 × 10−4 μM and 49.1 × 10−4 μM, respectively, in SK-MEL-28 cells following broadband visible light excitation. Using related cyclometalated Ru(II) complexes, we previously reported EC50 values ranging from 0.142 μM to 0.258 μM in SK-MEL-28 and HL60 cells following broadband visible light excitation [20]. Using [Os(phen)2(IP-nT)]Cl2 complexes related to ML18J03, with varying thiophene chain lengths (nT), we also reported EC50 values following broadband visible light excitation ranging from 1 μM to 3 μM for Os-nT = 0 to 2, and 0.153 μM to 18 × 10−6 μM for Os-3T and Os-4T, respectively [8]. However, the low water solubility and extensive aggregation can be significant limitations for these compounds. Our ruthenium-based photosensitizer (TLD1433) currently being evaluated in clinical trials exhibits an EC50 value of 1.9 × 10−4 μM in SK-MEL-28 [7]. Other clinically approved PSs, such as Verteporfin (Visudyne; Bausch + Lomb, Laval, Canada) and Porfimer Sodium (Photofrin; Pinnacle Biologics, Bannockburn, IL) exhibit EC50 values of 0.61–1.21 µM and 4.5 µM, respectively [21,22]. To put the PDT efficacy of Mic-ML18J03 into perspective, a comparison with other reported micelles previously used for PDT can be made. C225-conjugated chlorin e6-loaded polymeric micelles have exhibited an EC50 value of 0.173 μM in A431 cells [23]. Furthermore, Protoporphyrin IX-lipid micelles exhibited an EC50 value of 35.6 μM in HeLa cells [24]. A folate-mediated and pH-responsive chidamide-bound micelle system encapsulating the PS pyropheophorbide-a also exhibited an EC50 value of 0.062 μM in A2780 cells [25]. While direct comparisons of EC50 do not take into consideration the wavelength, fluence and irradiance of photoexcitation, it is still evident that ML18J03 is a highly potent PS that is active in hypoxia and in normoxia. Micellar formulation of ML18J03 also improves water solubility and offers a more robust PDT response with significantly lower inter-assay variability. As such, this study proceeds to explore the ability of micellar formulation to significantly enhance the in vivo luminescence imaging options for ML18J03.