Engineering Liposomes and Nanoparticles for Biological Targeting

Abstract

Our ability to engineer nanomaterials for biological and medical applications is continuously increasing, and nanomaterial designs are becoming more and more complex. One very good example of this is the drug delivery field where nanoparticle systems can be used to deliver drugs specifically to diseased tissue. In the early days, the design of the nanoparticles was relatively simple, but today we can surface functionalize and manipulate material properties to target diseased tissue and build highly complex drug release mechanisms into our designs. One of the most promising strategies in drug delivery is to use ligands that target overexpressed or selectively expressed receptors on the surface of diseased cells. To utilize this approach, it is necessary to control the chemistry involved in surface functionalization of nanoparticles and construct highly specific functionalities that can be used as attachment points for a diverse range of targeting ligands such as antibodies, peptides, carbohydrates and vitamins. In this review we provide an overview and a critical evaluation of the many strategies that have been developed for surface functionalization of nanoparticles and furthermore provide an overview of how these methods have been used in drug delivery systems.

Facing the Design Challenges of Particle-Based Nanosensors for Metabolite Quantification in Living Cells

“…The various surface functionalization chemistries that can be used for nanoparticles are well-described in other reviews. 181,184,185 …”

Evaluating Nanoparticle Sensor Design for Intracellular pH Measurements

“…6 A number of nanoparticle-based pH-sensitive drug delivery systems are being reported every year where various surface ligands, e.g., folate and antibodies, are attached to the surface of nanoparticles for targeting overexpressed receptors. 6,7 However, there is very limited knowledge on the intracellular trafficking of these systems, particularly regarding the pH that the particles are experiencing after internalization. At present, it is just assumed that the pHsensitive drug delivery system ends up in acidic compartments, but this has not been tested, and it is reasonable to hypothesize that the targeting ligands used could have an effect on trafficking.…”

Liposome functionalization with copper-free “click chemistry”

“…The product was purified directly by column chromatography (95:5 CH 2 Cl 2 /MeOH) to yield the product as a colorless oil (114 mg, 73%). Analytical data: 1 extruding at least 20 times using a Lipex™ Extruder (Northern Lipids, Burnaby, BC, Canada) through polycarbonate membranes with a final pore size of 100 nm (Nuclepore, Pleasanton, CA, USA). Liposomes were then incubated with 5-TAMRA-PEG3-Azide (Baseclick, Tutzing, Germany) in methanol in a 10:1 ratio of BCN-lipid:azide unless stated otherwise (this 10:1 ratio is corrected for the amount of BCN-lipid facing the inside of the liposome and as such is not available for coupling).…”

“…The common strategy is to synthesize a new lipid that contains a reactive group that can react with a complementary reactive group on the ligand. Many different chemistries have been explored for surface modification [1]. Ideally, these reactions should be fast and specific and reaction conditions should be mild enough not to cause damage to the lipid membrane or to the ligand.…”