chapter  2
54 Pages

Dendrimer–Nanoparticle Conjugates in Nanomedicine

Understanding the influence of nanoparticle properties-critical nanoscale design parameter (CNDPs)—on clinical translationissues, such as pharmacokinetics (PKs), pharmacodynamics (PDs), bioaccumulation, excretion modes and toxicology, is of utmostimportance. These CNDPs include size, shape, surface chemistry, flexibility/rigidity, architecture and elemental composition. The ability to structure, control and engineer CNDPs is undoubtedlythe major challenge in the translation of nanoparticle-basedtherapeutics into approved clinical applications.Although progress in the application of nanotechnology has been dramatic and successful, substantial opportunities exist forthe development of future generation nanotherapeutics by improving upon certain recognized nanoparticle limitations associated with the present prototypes.6 Efforts are focused oncreating more complex platforms that integrate real-time diagnostic, imaging, targeting and therapy delivery features. Various colloidal inorganic nanoparticles that feature properties such as: (i) luminescence (e.g. semiconductor quantum dots (QDs)7; up-/down-conversion nanoparticles),8 (ii) magnetic properties (e.g. metal oxide nanoparticles)9 and (iii) plasmonic properties (e.g. noble metal nanoparticles)10 have been widely explored. For instance, various types of magnetic nanoparticles have awidespread range of applications such as in MRI as T1 and T2contrast agent,11 magnetically guided drug/gene delivery,12magnetic hyperthermia and magnetic biosensors.13 Up-/down-conversion nanoparticles and QDs have their niche in biological and medical imaging,14 Noble metal nanoparticles can be usedfor photothermal therapy,15 and bio-sensing.16Designing nanoparticles for molecular diagnosis and targeted therapy is of the utmost importance. Such systems have recently been described as Theranostics.17 The fundamental advantage of theranostic nanomedicine lies in the use of patient specific test results to tailor a treatment regimen producing improved outcomes, reduced costs, and fewer side effects. While both therapeutic nanostructures and imaging nanoparticles (NPs) have a long history, they have only recently begun to coalesce into the theranostic NPs. Currently a large number of therapeuticsare engaged in preclinical and clinical studies (Table 2.2).18