Abstract
Retinoblastoma is a malignant growth affecting retina. An original combination of modified Non-Markov and Gompertzian computational approaches is proven of being a reliable tool for prediction of tumor selective accumulation of the bivalent metal isotopes (25Mg, 43Ca, 60Co, 67Zn, …) — releasing nanoparticles in human retinoblastoma cells. This mathematical model operates with a starting point of the discriminative drug uptake caused by a gap-like distinction between the neighboring malignant and normal cell proliferation rates. This takes into account both pharmacokinetic and pharmacodynamic peculiarities of PMC16, fullerene-C60 based nanoparticles, known for their unique capabilities for a cancer-targeted delivery of paramagnetic metal isotopes followed by an essential chemotherapeutic effect. Being dependent on a tumor growth rate but not on the neoplasm steady state mass, a randomized level of drug accumulation in retinoblastoma cells has been formalized as a predictive paradigm suitable to optimize an ongoing PMC16 preclinical research.
Highlights
Acknowledgments: this work was performed due to an exceptional technical assistance kindly provided by Erasmus-Plus DK06811/2020 Program associates affiliated with the Southern Denmark University at Odense, Denmark, and, most by Ms Patricia Wladycziewski, SDU Erasmus chief supervising officer
Human retinoblastoma (RB) is found to be very sensitive to some metal paramagnetic isotopes due their ability to promote a so called magnetic isotope effects which, in turn, promotes a sharp inhibition of DNA repair in malignant cells along with a formation of shorted, and DNA repair inconsistent, DNA sequences [1,2,3,4]. This might be taken as a “hopeful pullout” for coming up with a new element in RB chemotherapy based on administration of 25Mg2+, 43Ca2+, 60Co2+, 67Zn2+ carrying/ releasing nanoparticles (NPs) once the RB cell does overexpresses the DNA Polymerase Beta, a target enzyme for the nuclear spin selective DNA repair [1, 5, 6]
The treatment efficacy is a nonmonotonic function of the relation between the cell generation time and the period of drug administration, with maximal occurring when the limiting host cell cycle length is a multiple of the chemotherapeutic period
Summary
Acknowledgments: this work was performed due to an exceptional technical assistance kindly provided by Erasmus-Plus DK06811/2020 Program associates affiliated with the Southern Denmark University at Odense, Denmark, and, most by Ms Patricia Wladycziewski, SDU Erasmus chief supervising officer. Human retinoblastoma (RB) is found to be very sensitive to some metal paramagnetic isotopes due their ability to promote a so called magnetic isotope effects which, in turn, promotes a sharp inhibition of DNA repair in malignant cells along with a formation of shorted, and DNA repair inconsistent, DNA sequences [1,2,3,4] This might be taken as a “hopeful pullout” for coming up with a new element in RB chemotherapy based on administration of 25Mg2+, 43Ca2+, 60Co2+, 67Zn2+ carrying/ releasing nanoparticles (NPs) once the RB cell does overexpresses the DNA Polymerase Beta, a target enzyme for the nuclear spin selective DNA repair [1, 5, 6]. As a sign of such paramagnetic impacts, a significant decrease of proliferation rates has been observed in Y79 and WERI-RB-1 retinoblastoma cell strains [2,3,4]
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