Adsorptive functionalization of Mesoporous Silica nanoparticles for photodynamic therapy

Abstract text (incl. figure legends and references)

One reason for cancer resistance is the increased level of the ABCG2 membrane transporter protein, being responsible for elimination of tumor therapeutics. Inhibition of this receptor is a promising approach to prevent their elimination.[1] If the ABCG2 receptor is blocked by an inhibitor, such as KO143, therapeutics cannot be released from the tumor cell. It was shown that co-administration of KO143 with Ce6 as photosensitizer increased the sensitivity of photodynamic therapy in vitro.[2] Due to the presence of ABCG2 on healthy cells, side effects may occur with systemic administration of inhibitors such as KO143.[3] Efficient transport of KO143 and Ce6 into cells can be achieved by sequential loading on mesoporous silica nanoparticles (MSN).

Figure 1: Adsorption of KO143 onto MSN-OH/MSN-NH2 and adsorption of Ce6 onto MSN-NH2.

Adsorption studies showed that KO143 was adsorbed from DCM on both MSN-OH and MSN-NH2. Ce6 was loaded on MSN-NH2 from DMF (Figure 1). FACS experiments of KO143-loaded MSN-OH particles co-incubated with free Ce6 demonstrated that Ce6 fluorescence intensity does not decrease in ABCG2-containing glioblastoma cells indicating that KO143 inhibits Ce6 ejection. If both molecules are to be loaded onto MSN-NH2, this can only be done sequentially due to the different solubilities: First the particle is loaded with Ce6 followed by KO143 adsorption. UV/Vis measurements show that Ce6 is desorbed from KO143 during adsorption. If Ce6 is covalently bound to the particle and then KO143 is adsorbed, no desorption can be detected. Based on these results, MSN-OH bound KO143 can prevent the ejection of Ce6 from ABCG2-containing glioblastoma cells. Covalent binding of Ce6 followed by adsorption of KO143 onto MSN-NH2 can ensure simultaneous delivery of both therapeutics.

[1] M. H. Hasanabady et al., J. Biosci. 2016, 41, 313–324. [2] P. Müller et al., J. Photochem. Photobiol. B Biol. 2020, 210, 111963. [3] A. Ganoth et al., Expert Opin. Drug Deliv. 2015, 12, 223–238.