Biocompatible ZnS:Mn quantum dots for reactive oxygen generation and detection in aqueous media

Quantum dots (QDs) are recently being envisioned as potential photosensitizers (PS) for photodynamic therapy (PDT) to treat cancer (Thakor and Gambhir 2013 ; Allison and Moghissi 2013 ; Chen et al. 2013 ), due to their flexible bioconjugation, biological targeting efficiency, high quantum yield (QY), broad absorption with relatively narrow, symmetric emission, and long-term stability (Sotelo-Gonzalez et al. 2013 ; Zhang et al. 2011 ; Zhuang et al. 2003 ; Shen et al. 2012 ). The availability of QDs whose optical properties can be tuned by size, composition, and doping has brought forth new pathways to produce reactive oxygen species (ROS), in particular singlet oxygen ( 1 O 2 ), by photochemical methods. As a proof of concept, many QDs have been tested, but a strong focus has been placed on CdSe and CdTe QDs. For instance, CdSe QDs can be used to sensitize molecular oxygen through a triplet energy transfer mechanism. They can produce a 1 O 2 QY of ~5 % in toluene (cf. 43 % in Pc4 PS used in clinical trials), and their optical properties can be tuned to treat both shallow- and deep-seated tumors (Samia et al. 2003 ). Shi et al. working with CdTe QDs electrostatically bound to meso -tetra(4-sulfonatophenyl)porphine dihydrochloride (PS) obtained a 1 O 2 QY of ca. 43 % (being ≥40 % reported for traditional PSs) (Shi et al. 2006 ). Nonetheless, they did not fully quantify their results. Still, the cytotoxicity and solubility in water of Cd-based QDs (despite extended efforts to modify their surface) remain a significant concern. In this regard, Hsiech et al. overcoated CdSe cores with ZnS, being then attached to a cyclometalated Ir complex-type sensitizer (Hsieh et al. 2006 ). Although the 1 O 2 QY in benzene was improved, it was the Ir complex that was directly excited instead of the QDs. It has been reported that ZnS shells greatly reduce the toxic effects of Cd-based QDs in live cells and provide an improved 1 O 2 QY (as high as 31 %) (Tsay et al. 2007 ; Kirchner et al. 2007 ). Nevertheless, they are still tested in non-aqueous solutions due mainly to the surface chemistry of the core material. We have thus investigated the possibility to omit the use of Cd-based cores and substitute their optical contribution by Mn doping in ZnS (Bhargava and Gallaguer 1994 ). Recently, Zhou et al. reported on the sensitizing effect of cysteine-capped Mn-doped ZnS (ZnS:Mn)/Si QDs via the 1 O 2 quenching method (Zhou et al. 2011 ), but the findings of this exploratory work need further confirmation. The omission of the Si coating and evaluation of the quantification process of 1 O 2 using ZnS:Mn QDs via photooxidation are still a challenge.