Magnetic Nanoparticles and Intracellular Delivery of Biopolymers

The development of intracellular systems for the delivery of biopolymers able to undergo targeted interactions with genes and proteins is a current task in contemporary biology and medicine [69, 85]. Recent years have seen signifi cant advances in the development of therapeutic molecules for the treatment of various human diseases: antisense oligonucleotides, peptide-nucleic acids, and small interfering RNAs, which undergo targeted interactions with genes [22, 66, 67]. Nonetheless, no agent based on biopolymers has yet been used in clinical practice because of the initially low level of passive penetration into target cells and the absence of any system for high-effi ciency targeted delivery [42, 88]. All known methods for transfecting biopolymers into eukaryotic and prokaryotic cells in vitro have a number of limitations on their in vivo uses: low delivery effi ciency and high toxicity [97]. In our view, magnetofection is a method with potential for transection of biopolymers because of the physiological nature of the intracellular biomolecule delivery process driven by a magnetic fi eld. Development of magnetic nanoparticles effectively binding biopolymers will allow the main problems associated with the use of therapeutic nucleic acids to be resolved. In addition, magnetofection can provide a high level of targeting for delivery into target tissues and provides the opportunity to monitor the distribution of magnetic nanoparticles in tissues and organs using tomographic imaging methods [48, 105]. 1. Transfection Methods 1.1 Synthetic nanoparticles. Chemical transfection reagents are currently widely used for drug delivery, cationic liposomes being the most popular of these systems. There are now more than 30 commercial varieties of cationic liposomes, which have been developed specially for the delivery of biopolymers, such as Lipofectamine 2000 [17]. The mechanism of delivery into cells consists of enveloping the negatively charged biopolymer in a lipophilic sheath which in turn mediates fusion with the cell membrane and the penetration of biopolymers into the cytoplasm in endosomes. Other transfection reagents have also been developed, such as membrane-penetrating peptides consisting of short amphipathic molecules carrying biopolymers across the lipid bilayer by an energy-independent means. The use of these methods provides signifi cant increases in the proportion of molecules entering cells, though there are some drawbacks. The use of peptides may lead to cell death because of the large number of channels opened. In vitro use of cationic liposomes has provided highly successful transfection of biopolymers into cells, though their in vivo use generally leads to lipoblastomas and deterioration in body status. 1.2 Virus vectors. Synthetic biopolymers are extremely unstable and their effects are terminated as soon as they are Magnetic Nanoparticles and Intracellular Delivery of Biopolymers