Drug delivery tumor-selective

DOX, as EPI seems to form fewer amounts of ROS and secondary alcohol metabolite, (ii) encapsulation of anthracyclines in uncoated or pegylated liposomes that ensure a good drug delivery to the tumor but not to the heart, (iii) conjugation of anthracyclines with chemical moieties that are selectively recognized by the tumor cells, (iv) coadministration of dexrazoxane, an iron chelator that diminishes the disturbances of iron metabolism and free radical formation in the heart, and (v) administration of anthracyclines by slow infusion rather than 5-10 min bolus (Table 1). Pharmacological interventions with antioxidants have also been considered, but the available clinical studies do not attest to an efficacy of this strategy. 

Tumor cells express many hydrolytic enzymes, particularly peptidases, some of which are partially specific for certain tumor types, e.g., plasmin, plasminogen activator protease, and cathepsins. A number of prodrug strategies have been developed for the tumor-selective delivery of cytotoxic drugs [45-47], as illustrated below with a few representative examples. 

In summary, capecitabine (1), an A -carbamate pyrimidine nucleoside prodrug of cytotoxic antimetabolite 5-fluorouracil, is an FDA-approved anticancer drug that can be administered orally. This compound uses a multilayer of prodrug strategies that not only avoids side effects arising from exposure of toxic metabolites to healthy tissue but is converted to 5-fluorouracil only by enzymes preferentially expressed in many cancer cell types, thus resulting in selective delivery of the drug to tumors. Capecitabine is marketed under the trade name of Xeloda for use in the treatment of metastatic colorectal and breast cancers and metastatic breast cancer that is resistant to paclitaxel or anthracycline therapies. 

Radiotherapeutics attack cancer by causing radiation damage to DNA in cells. The requirements differ from those for drug delivery because the radiotherapeutic can act at a distance and does not have to separate from the delivery particle. Radiotherapeutics can be selected to provide action over a range of distances, from tens of nanometers to hundreds of microns. Three radiotherapy modalities can be identified. Brachytherapy, most often used with beta-emitters, uses tightly enclosed radioactive material that is brought in close proximity to the tumor. A second modality is intravenous injection so that the radiopharmaceutical binds to the outside of the tumor cells or is taken up by the cell and irradiates from within. The third approach uses a carrier loaded with the radiotherapeutic that is transported to the vicinity of the target cells, and then released. 

Tumor-Speckle MAbs or Fragments. In recent years, MAbs have been identified as effective anticancer agents. Several MAbs have been approved for clinical uses since 1997, and many more are in clinical trials. MAbs are believed to have multifunctional mechanisms. Their high selectivity toward tumors makes them ideal targeting ligands for actively tumor-targeted drug delivery systems. 

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