Targeted Lipid Nanoparticles for Antisense Oligonucleotide Delivery

Author(s)

Petrilli, Raquel ^{[1, 2]} ; Eloy, Josimar O. ^{[1, 2]} ; Marchetti, Juliana M. ^[1] ; Lopez, Renata F. V. ^[1] ; Lee, Robert J. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, BR-14049 Ribeirao Preto, SP - Brazil

^[2] Ohio State Univ, Coll Pharm, Columbus, OH 43210 - USA

• Document type: Journal article
• Source: CURRENT PHARMACEUTICAL BIOTECHNOLOGY; v. 15, n. 9, p. 847-855, 2014.
• Web of Science Citations: 9

Abstract

Antisense oligonucleotides (AS-ODNs) are short, single-stranded DNA molecules designed to bind specifically to a target messenger RNA (mRNA) and down-regulate gene expression. Despite being a promising class of therapeutics for a variety of diseases, they face major hurdles limiting their clinical application, including low intracellular delivery and poor in vivo stability. Among strategies available to enhance delivery, lipid nanoparticles have gained considerable attention. Active targeting of carriers of AS-ODNs is likely to further enhance delivery efficiency. For that, ligands for overexpressed receptors on the cell surface can be linked to the lipid nanoparticle, facilitating intracellular uptake, resulting in improved efficacy and reduced systemic toxicity. These include cell penetrating peptides (CPPs), transferrin, folate, oligosaccharides, polysaccharides and antibodies. Although targeted-lipid nanoparticles have been shown to enhance intracellular delivery and therapeutic effect of AS-ODNs, no clinical evaluation has been conducted yet. Therefore, more efforts are needed to turn these promising tools into clinical products. (AU)

• FAPESP's process: 12/10388-3 - Liposomes and immunoliposomes containing anticancer drugs: development, characterization and efficacy evaluation against breast cancer
• Grantee: Josimar de Oliveira Eloy
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/05362-8 - Functionalization of liposomes containing metformin and paclitaxel with trastuzumab: development, characterization and evaluation of efficacy against breast cancer
• Grantee: Josimar de Oliveira Eloy
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 13/15134-2 - Preparation of immunoliposomes for topical skin cancer treatment
• Grantee: Raquel Petrilli
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 12/23764-3 - Topical application of liposomes containing Cetuximab: the effect of physical skin penetration enhancement techniques for cutaneous squamous cell carcinoma
• Grantee: Raquel Petrilli
• Support Opportunities: Scholarships in Brazil - Doctorate