Institute for Bionanotechnology and Medicine IBNAM

Urbana, IL, United States

Institute for Bionanotechnology and Medicine IBNAM

Urbana, IL, United States
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Damiano M.G.,Northwestern University | Mutharasan R.K.,Feinberg Cardiovascular Research Institute | Tripathy S.,Northwestern University | McMahon K.M.,Northwestern University | And 3 more authors.
Advanced Drug Delivery Reviews | Year: 2013

High density lipoproteins (HDLs) are dynamic natural nanoparticles best known for their role in cholesterol transport and the inverse correlation that exists between blood HDL levels and the risk of developing coronary heart disease. In addition, enhanced HDL-cholesterol uptake has been demonstrated in several human cancers. As such, the use of HDL as a therapeutic and as a vehicle for systemic delivery of drugs and as imaging agents is increasingly important. HDLs exist on a continuum from the secreted HDL-scaffolding protein, apolipoprotein A-1 (Apo A1), to complex, spherical "mature" HDLs. Aspects of HDL particles including their size, shape, and surface chemical composition are being recognized as critical to their diverse biological functions. Here we review HDL biology; strategies for synthesizing HDLs; data supporting the clinical use and benefit of directly administered HDL; a rationale for developing synthetic methods for spherical, mature HDLs; and, the potential to employ HDLs as therapies, imaging agents, and drug delivery vehicles. Importantly, methods that utilize nanoparticle templates to control synthetic HDL size, shape, and surface chemistry are highlighted. © 2012 Elsevier B.V.

McMahon K.M.,Northwestern University | McMahon K.M.,Institute for BioNanotechnology and Medicine IBNAM | Mutharasan R.K.,Feinberg Cardiovascular Research Institute | Tripathy S.,Northwestern University | And 15 more authors.
Nano Letters | Year: 2011

We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy that combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy, and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery. © 2011 American Chemical Society.

McMahon K.M.,Northwestern University | Thaxton C.S.,Northwestern University | Thaxton C.S.,Institute for Bionanotechnology and Medicine IBNAM | Thaxton C.S.,Robert rie Comprehensive Cancer Center
Expert Opinion on Drug Delivery | Year: 2014

Introduction: RNA interference (RNAi) is a powerful mechanism for gene silencing with the potential to greatly impact the development of new therapies for many human diseases. Short interfering RNAs (siRNAs) may be the ideal molecules for therapeutic RNAi. However, therapeutic siRNAs face significant challenges that must be overcome prior to widespread clinical use. Many efforts have been made to overcome the hurdles associated with systemic administration of siRNA; however, current approaches are still limited. As such, there is an urgent need to develop new strategies for siRNA delivery that have the potential to impact a broad spectrum of systemic diseases. Areas covered: This review focuses on the promise of siRNA therapies and highlights current siRNA delivery methods. With an eye toward new strategies, this review first introduces high-density lipoprotein (HDL) and describes its natural biological functions, and then transitions into how HDLs may provide significant opportunities as next-generation siRNA delivery vehicles. Importantly, this review describes how synthetic HDLs leverage the natural ability of HDL to stabilize and deliver siRNAs. Expert opinion: HDLs are natural nanoparticles that are critical to understanding the systemic delivery of therapeutic nucleic acids, like siRNA. Methods to synthesize biomimetic HDLs are being explored, and data demonstrate that this type of delivery vehicle may be highly beneficial for targeted and efficacious systemic delivery of siRNAs. © 2014 Informa UK, Ltd.

Foit L.,Northwestern University | Foit L.,Institute for BioNanotechnology and Medicine IBNAM | Giles F.J.,Northwestern University | Gordon L.I.,Northwestern University | And 2 more authors.
Expert Review of Anticancer Therapy | Year: 2014

High-density lipoproteins (HDLs) are a diverse group of natural nanoparticles that are most well known for their role in cholesterol transport. However, HDLs have diverse functions that provide significant opportunities for cancer therapy. Presented is a focused review of the ways that synthetic versions of HDL have been used as targeted therapies for cancer, and as vehicles for the delivery of diverse therapeutic cargo to cancer cells. As such, synthetic HDLs are likely to play a central role in the development of next-generation cancer therapies. © 2015 Informa UK Ltd.

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