Cisplatin – A more Efficient Drug in Combination with Radionuclides?

Abstract

Aim The combination of conventional chemotherapeutic drugs with radionuclides or external radiation is discussed for a long period of time. The major advantage of a successful combination therapy is the reduction of severe side effects by decreasing the needed dose and simultaneously increasing therapeutic efficiency. Methods In this study, pUC19 plasmid DNA was incubated with the cytostatic drug cisplatin and additionally irradiated with 99mTc, 188Re and 223Ra. To verify the contribution of possibly excited platinum atoms to the emission of Auger electrons we determined DNA damages, such as single- and double strand breaks. Results The threshold concentration value of cisplatin, which was tolerated by pUC19 plasmid DNA was determined to be 18–24 nM. Nevertheless, even at higher dose values (>100 Gy) and simultaneous incubation of cisplatin to 200 ng plasmid DNA, no significant increase in the number of induced single- and double-strand breaks was obtained, compared to the damage solely caused by the radionuclides. Conclusion We thereby conclude that there is no direct dependence of the mechanism of strand break induction to the absence or presence of platinum atoms attached to the DNA. Reported increasing DNA damages in therapy approaches on a cellular level strongly depend on the study design and are mainly influenced by repair mechanisms in living cells. Nevertheless, the use of radioactive cisplatin, containing the Auger electron emitter 191Pt, 193mPt or 195mPt, is a bright prospect for future therapy by killing tumor cells combining two operating principles: a cytostatic drug and a radiopharmaceutical at the same time.

Combining Cisplatin with Different Radiation Qualities—Interpretation of Cytotoxic Effects In Vitro by Isobolographic Analysis

“…Recently, our group published a study that investigated the effects of cisplatin in combination with radionuclides using plasmid pUC19 as a biophysical model. No significant increase in the number of DNA strand breaks has been found [32].…”

Recent Metal Nanotheranostics for Cancer Diagnosis and Therapy: A Review

“…Zhang et al [112] found that the radiation doses could be physically enhanced when combining the platinum nanoparticles coated with bovine serum albumin (BSA), Pt@BSA NPs, for use in radiotherapy. Also, studies showed that the presence of platinum nanoparticles when cell cultures were irradiated could result in strongly enhanced breaks in DNA, especially DSBs, mediated by water radicals which may originate from the inner-shell excitation of platinum atoms [50,113,114]. In other studies, Gutiérrez et al [115] discussed the enhanced effect of radiation on cervicaluterine cancer cells (HeLa) when the cancer cells were treated with PEGylated PtNPs functionalized with a fluorescent marker in combination with γ-rays.…”

Nanomaterials as Theranostic Agents for Cancer Therapy

“…In another study, Zhang et al discovered the physical enhancement of the radiation when combined with platinum NPs coated with bovine serum albumin (BSA) (Pt@BSA) NPs when used for radiotherapy . Water-mediated enhanced breaking in DNA was observed which originated from the inner-shell excitation of platinum atoms when the cell was irradiated in the presence of platinum nanoparticles. ,, Gutiérrez de la Rosa et al explored the intensified effect of radiation on the HeLa cell line upon treatment with PEGylated PtNPs when functionalized with a fluorescent marker in addition to γ-rays . The increment in radiation dose of nanoparticles decreased the cell viability of cancerous cells.…”