Cisplatin cyclodextrin complexes as potential free radical chemoradiosensitizers for enhanced cisplatin treatment of cancers: a quantum mechanical study

It has been shown in this study that {CisPt@n]CD} complexes formed from the anti-cancer drug cisplatin (CisPt) and cyclodextrins (n]CD) can be a source of Pt based free radicals such as (H₃N)₂PtCl· and (H₃N)₂Pt·· species in water within a radiation environment which can produce hydrated electrons. Encapsulating CisPt within the n]CD host takes advantage of the previously described drug delivery and reduced side effect advantages of CDs. Based on quantum mechanical modelling and literature results from other studies, it is predicted that {CisPt@γ]CD} and the analogous 2-hydroxypropylβ]cyclodextrin (HPBCD) complex {CisPt@HPBCD} may interact with serum albumin and engage in an enhanced permeation and retention mechanism in solid tumours, offering further synergistic advantages for radiation-{CisPt@γ]CD} or -{CisPt@HPBCD} regimens over that of the conventional radiation-CisPt regimens in current use in anti-cancer chemoradiotherapies. Comparisons and possible advantages are made with the previously documented chemoradiosensitizing properties of the analogous cucurbit7]uril based{CisPt@7]CB} complex with the {CisPt@γ]CD} and {CisPt@HPBCD} complexes suggest that all three complexes may have different and tailorable anti-tumour uses for a range of different chemotherapeutic environments or protocols.