Abstract
The delivery of targetable synthetic vectors that can carry a variety of drugs, proteins, and nucleic acids, such as DNA and small interfering RNA (siRNA), to mammalian cells is important as a potential therapeutic system that avoids the problems that are associated with viruses. The so-called multifunctional nanocarriers that are equipped with several functions, such as targetability, shelter from the immune system, and opsonization, and are capable of delivering payload across the nuclear envelope, have been synthesized. To improve transfection efficiency, a group of novel peptides have been attached to the surface of the carrier that will enhance endosomal escape and promote nuclear entry. The targeting of tropomyocin receptor kinase B (TrkB) with ligands enhances uptake in spiral ganglion cell culture. Treatment cargos have included growth factors such as the Math-1 gene, short hairpin RNA, and steroids. The problems with current synthetic nanocarriers are poorer selectivity, internalization, and transfection rate compared with viral vectors. Within a few years, when the synthetic vectors have been optimized, the first human drugs/proteins/gene product-based therapies will become available in a phase I study.
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