conclusions compared with monotherapy, adding ribavirin to treatment is more effective in removing hepatitis c virus from the bloodstream in patients with thalassemia, it is also more effective in reducing the relapse rate after treatment. except the increase in blood transfusion, there was no significant increase in side effects followed by adding ribavirin. results three randomized clinical t...

Targeted drug delivery to selected sites allows reduced toxicity, enhanced efficiency and interchangeable target potential [Langer, R. (2001) Science 293, 58-59 and Molema, G. & Meijer, D. K. F., eds. (2001) Drug Targeting (Wiley-VCH, Weinheim, Germany)]. We describe a bipartite drug-delivery system that exploits (I) endogenous carbohydrate-to-lectin binding to localize glycosylated enzyme conj...

Human cytomegalovirus (HCMV) is a prevalent virus that infects up to 90% of the population. The goal of this research is to determine if small molecular prodrug substrates can be developed for a specific HCMV encoded protease and thus achieve site-specific activation. HCMV encodes a 256 amino acid serine protease that is responsible for capsid assembly, an essential process for herpes virus pro...

Spores of some species of the strictly anaerobic bacteria Clostridium naturally target and partially lyse the hypoxic cores of tumors, which tend to be refractory to conventional therapies. The anti-tumor effect can be augmented by engineering strains to convert a non-toxic prodrug into a cytotoxic drug specifically at the tumor site by expressing a prodrug-converting enzyme (PCE). Safe doses o...

Tenofovir-disoproxil-fumarate (TDF) is a double ester prodrug which enables intestinal uptake of tenofovir (TFV) after oral administration in humans. In this study, prodrug stability was monitored in situ in the human intestine and in vitro using biorelevant media. In fasted state human intestinal fluids, the prodrug was completely degraded within 90 min, resulting in the formation of the mono-...

The gene for the bacterial enzyme carboxypeptidase G2 (CPG2) was expressed internally in mammalian cells. Mammalian-expressed CPG2 had kinetic properties Indistinguishablefrom bacterially expressed CPG2. Human tumor cell lines A2780, SK-OV-3 (ovarian adenocarcinomas), LS174T, and WLDr(colon carcinomas) were engineered to express con stitutively either CPG2 or bacterial 13-galactosidase. These c...

New treatments are needed for brain metastasis, which is associated with high morbidity and mortality. Two novel cellular and gene therapy modalities were evaluated in xenograft models for human breast cancer. The individual and especially the combined treatments with alloreactive cytotoxic T lymphocytes and replicating retroviral vectors coding for prodrug activating enzymes followed later wit...

The preparation of PEGylated fluorescent nanoparticles (NPs) based on atom transfer radical polymerization (ATRP) and “click chemistry” in one-pot synthesis is presented. First, poly(p-chloromethyl styrene-alt-N-propargylmaleimide) (P(CMS-alt-NPM)) copolymer was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. Subsequently, the azido-containing fluorene-based...

The tumor microenvironment is notably enriched with a broad spectrum of proteases. The proteolytic specificities of peptide substrates provide modular chemical tools for the rational design of cell-impermeable prodrugs that are specifically activated by proteases extracellularly in the tumor microenvironment. Targeting cell-impermeable prodrug activation to tumor microenvironment will significa...

A reliable approach is developed to formulate a targeted lipid-coated nanomedicine based on UCNP and co-loaded with CO-prodrug vitamin E, which can convert NIR light UV photon release CO for synergistical cancer therapy E.