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Highly uniform and multifunctional hollow mesoporous silica nanocages that combined excellent properties (good biocompatibility, fluorescence imaging, drug delivery, and dual-mode cancer therapy) in one single system were synthesized. Dye molecules labeled in the nanocages could be used as traceable detectors in fluorescence imaging. A chemotherapeutic drug, doxorubicin (DOX), has been loaded into the nanocages with a high storage capacity due to the large cubic cavities and could be released through the penetrating mesoporous channels in a sustained fashion. Hematoporphyrin molecules were also covalently doped in the nanocages and allowed for photodynamic therapy. More importantly, a cooperative, synergistic therapy combining chemotherapy and photodynamic therapy exhibited high therapeutic efficacy for cancer therapy in vitro.

Most nucleoside analogs require stepwise phosphorylation to the respective triphosphate metabolites to exert their pharmacological activity. L-and D-dCyd analogs are phosphorylated by cytoplasmic deoxycytidine kinase, and dThd analogs are phosphorylated by cytoplasmic thymidine kinase to the monophosphate metabolites. L-FMAU can be phosphorylated by both cytoplasmic deoxycytidine kinase and cytoplasmic thymidine kinase. dCyd analog monophosphates are further phosphorylated by cytidine/uridine monophosphate kinase to the respective nucleoside diphosphate metabolites, whereas the dThd analogs are phosphorylated by thymidine monophosphate kinase (1, 2, 15, 16). Conversion of L-deoxynucleoside analog diphosphates to the pharmacologically active L-deoxynucleoside triphosphate metabolites remains largely unexplored; however, NDPK, which could phosphorylate naturally occurring nucleoside diphosphates, has been assumed to play a role (17-21). The last step of phosphorylation is of potential importance, because analogs like L-Fd4C, L-OddC, L-SddC, and ddC accumulate in the cells as diphosphate metabolites indicating inefficiency of the responsible enzyme (6,(22)(23)(24). However, L-FMAU is efficiently metabolized to .Eight isoforms of NDPK have been isolated in humans, of which nm23-H1 and nm23-H2 have been shown to be cytoplasmic, and are capable of phosphorylating nucleoside diphosphates (26,27). DR-nm23 (28), nm23-H4 (29) and nm23-H6 (30) are localized in the mitochondria, and nm23-H5 is testisspecific (31). Activities of nm23-H7 and nm23-H8 in terms of nucleoside diphosphate phosphorylation are not known (NCBI accession numbers Q9Y5B8 and XP_004705, respectively). NDPKs utilize ATP or other nucleoside triphosphates as a phosphate donor and transfer the phosphate residue onto nucleoside diphosphate via a phosphohistidine intermediate (ping-pong mechanism) (32, 33).Other enzymes that are capable of phosphorylating nucleoside diphosphates are creatine kinase, 3-phosphoglycerate kinase, pyruvate kinase, phosphoenolpyruvate carboxykinase, and adenylosuccinate kinase (34 -36). Based on the high rates of hydrolysis of the phosphate bonds of the donor compounds

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