| dc.description.abstract | Nanocarriers, particles in the size range of 1 to 1000 nanometer, are the application of nanotechnology to drug delivery. Delivery of therapeutic agents through these nanoparticles allows tailoring of physicochemical and biological qualities to provide control over the pharmacokinetic and pharmacodynamic properties of the therapeutics. Nanoparticle-based drug delivery is most often applied to solid cancers and classes of nanocarriers include polymer conjugates, liposomes, micelles, polymersomes and dendrimers. Drug delivery strategies can be broadly classified into triggered drug release, passive targeting and active targeting. Several studies have demonstrated that active targeting increases nanoparticle internalization into cells but not tissue localization, being largely reliant upon the Enhanced Permeability and Retention (EPR) effect. As such, few actively targeted nanoparticles have made it into clinical trials and none have made it into medical practice. Actively targeted nanocarriers that have been reported to have entered clinical trials include BIND-014, CALAA-01, MBP-426, PK2, MCC-465, Lipovaxin-MM, SGT-53 and MM-302, most of which are currently in phase I trials. Most of these nanoparticles feature well-established nanocarriers and targeting ligands, all of which are targeted towards receptors that internalize upon antigen binding. All of the actively targeted nanoparticles have been designed for the treatment of solid cancers and most target the cancer cells directly to deliver therapeutics that would otherwise exhibit a short half-life, low tumor accumulation and/or adverse side-effects. The only exception, Lipovaxin-MM, is designed for immunotherapy of cancer through delivery of antigens and interferon-gamma to dendritic cells. Actively targeted nanoparticles were demonstrated to have similar biodistribution, tumor localization and clearance to passively targeted nanoparticles. Nevertheless, in most cases active targeting showed improved cellular uptake, tumor retention and antitumor efficacy in in vitro, and in some cases in vivo, studies. While these actively targeted nanoparticles showed promising results, there has not yet been a definitive proof-of-principle of the clinical benefit of active targeting in humans and further studies are needed to fully assess the capabilities, benefits and complications of active targeting. | |
