Polymeric Nanostructures for Imaging and Therapy.

Abstract

Medical diagnosis and therapy are essential for providing patients with proper care, although inefficient diagnosis and therapy are usually associated with either improper detection of the diseases, unsatisfactory therapeutic outcomes and/or serious adverse reactions. Advances in the design of various diagnostic and therapeutic agents, and the recent trend of utilizing molecules for both therapeutic and diagnostic applications (i.e. theranostics), still have not achieved the maximum benefits of controlling the navigation and biodistribution of these molecules within the biological system. The key challenges towards the use of these agents, from small molecules to macromolecular drugs (e.g. natural, proteins and nucleic acids-based drugs, or synthetic, polymer-based conjugates, carriers or other systems), are, for example, the loss of activity via rapid clearance or degradation, inefficient delivery to the target sites, and inappropriate probing of the disease states, dependent on the particular disease and its location in the body. The concept of nanotechnology has been initiated early in 1959 by Richard Feynman in his famous historical talk at Caltech “There’s Plenty of Room at the Bottom”, with introduction of the possibility of manipulating materials at the atomic and molecular levels.1 In 1974, Norio Taniguchi, at Tokyo University, first utilized the term “nanotechnology” referring to the design of materials on the nanoscale.2 In the early 1990’s and until now, the use of nanomaterials of different nature (organic and inorganic), and for various applications (multiple disciplines) has been greatly expanded, in particular, over the last couple of decades.3-4 In the medical field, nanotechnology has emerged to include non-invasive systems for probing of disease and also capable of carrying cargo for localized high concentration delivery, known as “nanomedicine”, with reduction of off-target effects. The use of nanomaterials, in particular polymeric nanostructures, has demonstrated efficiency in improving delivery of diagnostic and therapeutic agents to the target sites, and the feasibility of incorporating several therapeutic/diagnostic/targeting moieties within specific compartments of the nanoparticles, with control of their navigation in the body and to the target sites. Further understanding of the nature and microenvironments of biological systems (e.g. different pH, temperature, permeability, drainage, or overexpressing proteins, enzymes or receptors), and the barriers towards the delivery of various moieties to their destinations, which could be either intra- or extracellular, has aided the design of nanomaterials that could evade the various physiological barriers. Selective delivery to the site of the disease can increase the therapeutic efficacy, imaging contrast and accuracy, reduce adverse reactions, and reduce the dose and cost of medications. Initially, platform technologies were the target for nanostructure designs, but with the complications of biological systems, it has been recognized over the past decade that disease- and patient-specific medical treatment is needed for efficacy—this review highlights a few examples developed within the past couple of years, with a focus on in vivo studies together with novel designs and significant advances in syntheses. The advantages of polymeric nanostructures over other types of nanomaterials are based upon the flexibility over which their structures can be modified to yield materials of various compositions, morphologies, sizes, surface properties, with possibility of hierarchical assembly of several nanomaterials of various components into one construct that can be accommodated with a variety of therapeutic, diagnostic and/or targeting moieties, within selective compartments of the nanodevices. High efficiency in diagnosis and treatment of diseases and improving patient quality of life and compliance can be achieved through understanding the molecular events associated with various diseases, and combining the advances in the design of therapeutic and diagnostic agents and nanomaterials, together with the innovative instruments utilized for monitoring these agents. This review will focus on several recent advances in the design of polymeric nanoparticles that have been utilized for delivery of diagnostic and/or therapeutic agents, and the various barriers towards the clinical development of these materials. After a brief overview of the capabilities and challenges with medical imaging and therapy, in general, disease-specific examples of polymer nanoparticles designed specifically to overcome the challenges and address unmet medical needs will be discussed in detail.