Bioresponsivity

Takae S, Miyata K, Oba M, Ishii T, Nishiyama N, Itaka K, Yamasaki Y, Koyama H, Kataoka K (2008) PEG-detachable polyplex micelles based on disulfide-linked block catiomers as bioresponsive nonviral gene vectors. J Am Chem Soc 130 6001-6009... 

LiEL Y, SHANY s, SMIRNOFF p and SCHWARTZ B (1999) Estrogen increases 1,25-dihydroxyvitamin D receptors expression and bioresponse in the rat duodenal mucosa. Endocrinol 140, 280-85. 

Natural viruses provide us with perfect demonstrations of how effective nucleic acid transfer into mammalian cells can proceed. The secret of their efficiency is their dynamic, bioresponsive behavior during delivery, which distinguishes them from classic synthetic nanoparticles. Thus, it has been tempting for us and many research colleagues [69, 92, 164, 188-194] to design nucleic acid nanoparticles with virus-like characteristics ( synthetic viruses ). 

Polymers can be designed to be bioresponsive and to change their properties in various biological compartments, for example their conformation and charge. They may contain chemical bonds that are cleaved under temporal or spatial control, or they may associate/dissociate in a controlled fashion. Bioresponsiveness of the carrier is required in several steps of the transport (Fig. 1). 

The following sections discuss how polymers and polyplexes can be chemically designed to be bioresponsive in three key delivery functions (1) polyplex surface shielding, (2) interaction with lipid bilayers, and (3) polyplex stability. 

Fig. 1 Bioresponsive polyplexes. (a) Systemic circulation of shielded polyplexes in blood stream and attachment to cell surface receptor (b) endocytosis into endosomes, deshielding by cleavage of PEG linkers and activation of membrane-destabilizing component by acidic pH or other means (c) endosomal escape into cytosol (d) siRNA transfer to form a cytosolic RNA-induced silencing complex complex (e) cytosolic migration and intranuclear import of pDNA (/) presentation of pDNA in accessible form to the transcription machinery...

Meyer M, Dohmen C, Philipp A, Kiener D, Maiwald G, Scheu C, Ogris M, Wagner E (2009) Synthesis and biological evaluation of a bioresponsive and endosomolytic siRNA-polymer conjugate. Mol Pharmaceutics 6 752-762... 

The goal of this research is to develop a new class of bioresponsive materials that undergo rapid, large-magnitude, volume-phase transitions in response to specific biological stimuli. Our approach to these materials is based on two fundamental aspects of hydrogels (1) hydrogel solvation/desolvation thermodynamics can be perturbed... and... 

A second point of significance is that this work will lead to a new class of bioresponsive materials for a host of applications. Initial applications target biosensors and bioassays colloidal materials provide tremendous versatility in biosensor design. For... 

Smith JR, Kholodovych V, Knight D, Welsh WJ, Kohn J (2005) QSAR models for the analysis of bioresponse data from combinatorial libraries of biomaterials. QSAR Comb Sci 24 99-113... 

S. Scharbert, N. Holzmann and T. Hofmann, Identification of the astringent taste compounds in black tea infusions by combining instrumental analysis and human bioresponse, J. Agric. Food Chem., 52 (2004) 3498-3508. 

Keywords Bioresponsive Cationic polymers Chemical programming DNA ... 

Bioresponsive Polyplex Shielding and Endosomal Escape 3.1 Reversible Polyplex Shielding... 

Brenner-WeiB, G. and U. Obst. 2003. Approaches to bioresponse-linked instrumental analysis in water analysis. Anal. Bioanal. Chem. 377 408M-16. 

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