Dendrimers are unique macromolecules with highly branched structure and globular shape. Molecular size, structure, and properties of dendrimers are highly controllable. These characteristics of dendrimers are very useful for the precise design of drug carriers and hence their application to drug delivery has been actively attempted. A brief description of dendrimers is given and present status of dendrimer-based design of drug carriers is viewed. While some of widely used dendrimers are shown to be toxic, biodegradable and biocompatible dendrimers have also been developed. Various kinds of dendrimer-drug conjugates have been prepared using polyamidoamine, polyphenylether, and polyester dendrimers and anticancer drugs such as doxorubicin, methotrexate, and 5-fluorouracil. While some of these conjugates exhibit toxicity against cancer cells, their activity is still to be improved. Dendrimers with hydrophobic core and hydrophilic shell have been designed as unimolecular micelles. These dendrimers are able to encapsulate hydrophobic drugs in their interior and release them slowly. Dendrimers with an interior of basic environment have ability to encapsulate acidic drugs, such as inethotrexate. Surface modification of dendrimers has also been attempted. Various kinds of ligands, such as sugars and folate residues, have been attached to dendrimers. These dendrimers may be useful as drug carriers with target cell specificity. In addition, surface modification of dendrimers with poly (ethylene glycol) has been tried to obtain dendrimers with biocompatible surface. Rationally and precisely designed, dendrimer-based carriers may realize an accurate delivery of drugs to the target site and lead to an enhanced efficacy of drugs.

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Restenosis after coronary intervention still remains a serious problem in clinical cardiology. Recent advances in nanotechnology have enabled us to selectively deliver an antiproliferative drug to the balloon-injured artery. Here we report our results with NK911 that is a doxorubicin containing nanocapsule and is characterized to selectively accumulate in vascular lesions with increased permeability. We first confirmed by Evans-blue staining that in the rat carotid artery, vascular permeability was markedly increased at least for one week after balloon injury. We then examined the inhibitory effect of NK911 on the restenotic changes 4 weeks after the injury either in the normal artery (single injury protocol) and in the arteriosclerotic artery that had been induced by a previous balloon injury (double injury protocol). NK911 was intravenously administered only three times (immediately after, and 3 and 6 days after the injury) at three different doses (0.1, 1.0 and 10 mg/kg). Corresponding doses of doxooruhicin alone (0.016, 0.16, 1.6 mg/kg) were also administered in the same manner. In both protocols. NK911 dose-dependently suppressed neointimal formation (P<0.001, n=6 each). Immunohistochemical examination demonstrated that the inhibitory effect of NK911 was mainly due to suppression of vascular smooth muscle proliferation. Measurement of vascular concentrations of doxorubicin demonstrated that NK911 effectively delivered the drug to the balloon-injured carotid arteries. Finally, NK911 was well tolerated without any systemic adverse effects. Thus, the treatment with nanocapsules containing antiproliferative agents may be a novel and promising strategy for the prevention of restenosis after balloon angioplasty.

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Oligonucleotides attaching a reactive molecule may cause irreversible change to the target sequence at the reactive site. Inhibition of transcription, site-directed mutagenesis (or site-directed manipulation of genes) at the specific site has been proposed as a new tool of biotechnology with the use of a triplex-forming oligonucleotide. Thus, the oligonucleotides are regarded as a tool for intracellular DOS of useful reactive molecules. This review deals with development of a new alkylating group with high selectivity toward cytosine as well as new non-natural base analogs for the formation of stable non-natural triplexes.

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Molecular chaperones serve to prevent protein misfolding and aggregation in the cell. Chaperones act by binding transiently to exposed hydrophobic surfaces in target proteins in a manner that is regulated by ATP-induced conformational changes. Some molecular chaperones(heat-shock proteins, HSP) are peptide-binding proteins such as antigenic peptides that are generated within cells. Molecular chaperons play very important role in antigen presentation and cross-presentation. The immunological properties enable them to be used in new immunotherapies of cancers and infections. Chaperone can prevent the deposition of amyloid aggregates that induce Alzheimer's or Huntington disease. In biotechnology, there is much interest in producing large amounts of biologically active recombinant proteins. In many cases, however, problems such as formation of insoluble inclusion bodies are encountered. To overcome this problem, molecular chaperon and artificial molecular chaperone are used in vitro as refolding aids of proteins. In this paper, we summarized the function of molecular chaperones and application to biotechnology and medicine. Artificial molecular chaperones are also discussed.

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