title: Surface decorations of poly(amidoamine) dendrimer by various pendant moieties for improved delivery of nucleic acid materials.
abstract: In recent years, the discovery of novel nucleic acid-based drug candidates (e.g., siRNA and miRNA) and the groundbreaking studies for somatic cell reprogramming into a state of pluripotency have led to reconsideration for the use of human gene therapy as a new paradigm with great therapeutic potential. However, the success of gene therapy is dependent on overcoming intra- and extracellular barriers hampering the efficient delivery of nucleic acid therapeutics into the target cells or tissues. Despite relatively low transfection efficiency, great attention has been directed to cationic polymers and dendrimers due to their ability to condense DNA and RNA molecules into nano-sized particles which is a necessary prerequisite for efficient transfer of nucleic acids into cells. These gene carriers show remarkable adaptability and significant capacity to transfer larger sizes of nucleic acid materials. Polyamidoamine (PAMAM) dendrimer has been employed as non-viral gene carrier due to its globular shape and well-defined structure containing abundant amino surface groups which provide possibility for surface decoration of the dendrimer via the conjugation of various moieties. In this review, we have brought out the various functionalization strategies of the PAMAM surface amines using different pendant moieties such as amino acids, proteins, cyclodextrins, and hydrophobic units in order to overcome intra- and extracellular barriers. These surface-decorated dendrimers possessing favorable properties provide substantial information and insight for redesigning existing dendrimers and polymers. By understanding the role played by the conjugated moieties, more efficient and novel designs of gene vehicles may be possible.
authors.affiliation: Department of Pharmaceutical Biotechnology, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran; Center for Nanotechnology in Drug Delivery, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: dehshahria@sums.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Dehshahri
authors.affiliation: Department of Medicinal Chemistry, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Sadeghpour
mesh_terms: D050091:Dendrimers / Q000737:chemistry*; D009696:Nucleic Acids / Q000008:administration & dosage*; D010316:Particle Size; D011073:Polyamines / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D050091:Dendrimers; D009696:Nucleic Acids; C531249:Poly(amidoamine); D011073:Polyamines
keywords: Dendrimer; Gene delivery; Gene therapy; Nanoparticle; Non-viral vector; Surface modification