Cellular internalization of inorganic, lipidic and polymeric nanoparticles is of great significance in the quest to develop effective formulations for the treatment of high morbidity rate diseases. Understanding nanoparticle–cell interactions plays a key role in therapeutic interventions, and it continues to be a topic of great interest to both chemists and biologists. The mechanistic evaluation of cellular uptake is quite complex and is continuously being aided by the design of nanocarriers with desired physico-chemical properties. The progress in biomedicine, including enhancing the rate of uptake by the cells, is being made through the development of structure–property relationships in nanoparticles. We summarize here investigations related to transport pathways through active and passive mechanisms, and the role played by physico-chemical properties of nanoparticles, including size, geometry or shape, core-corona structure, surface chemistry, ligand binding and mechanical effects, in influencing intracellular delivery. It is becoming clear that designing nanoparticles with specific surface composition, and engineered physical and mechanical characteristics, can facilitate their internalization more efficiently into the targeted cells, as well as enhance the rate of cellular uptake.

Designing dendrimers that are monodisperse hyperbranched macromolecules and offer significant potential in numerous scientific fields, is becoming a major topical area in modern research. Among the challenges of the 21st century, synthetic methodologies that increase efficiency of conversion and a greener chemistry approach, are expected to lead the way in the quest to build novel nanomaterials. The recent entry of so-called “click” reactions that include Diels–Alder, Cu^I -catalyzed Huisgen cycloaddition and thiol-ene coupling, have generated real stimulus not only in developing elegant materials of choice, but also in making the leap to industrial scale build-up of dendritic macromolecules. This tutorial review takes on the task of demonstrating the simplicity of these “click” reactions and the advantages they offer from a synthetic view point in developing mono- to multifunctional dendrimers. A brief introduction to “click” chemistry is followed by a chronological survey of developments in the field, and the impact these have had in designing novel dendritic macromolecules. The review is intended to introduce scientists to these highly efficient methodologies with demonstrated potential, and provide impetus for further growth of the area.

Miktoarm polymers are a relatively new and unique class of macromolecules, and constitute a topical area of research due to their intriguing properties which can be tailored by varying their polymer arms. Much emphasis has been placed in the recent past in developing synthetic methodologies to these star polymers, and examining their self-assembly in solution. This review summarizes the progress made in the area of miktoarm star polymers in terms of their synthesis, behavior in solution, and applications. The different synthetic strategies to construct a variety of miktoarm star polymers are described, and each methodology strikes a balance between ease of synthesis and control over the final architecture. The self-assembly of miktoarm polymers in solution is then elaborated, which is frequently studied as a function of either arm-length (an intrinsic property of the star) or the application of an external stimulus (pH, temperature, etc.). This is followed by an overview of the applications of these stars in areas including drug delivery.

The chemoselective [3+2] cycloaddition of an azide on to an alkyne, catalyzed by Cu¹, has become known as “click-chemistry”. The ease with which this reaction can be carried out and the formation of pure product without the need for further purification, offer a tremendous potential in developing monodisperse 1,4-disubstituted 1,2,3-triazole heterocycle based macromolecules of a diverse nature. The versatility of this approach in designing dendrimers or functionalizing them at the periphery with desired molecules has rekindled hopes in developing nanomaterials, at scales that can accelerate their entry into industrial usage.

The delivery of biologically active agents to the desired site in the body and intracellular organelles is still a big challenge despite efforts made for more than five decades. With the elaboration of synthetic methodologies to branched and hyperbranched macromolecules such as miktoarm stars and dendrimers, the focus has shifted to nanocarriers able to release and direct drug molecules to a desired location in a controlled manner. We present here recent developments in the field of targeted drug delivery with a focus on two specific macromolecular nanocarriers, dendrimers and miktoarm stars, and provide examples of these nanocarriers tested in different biological systems. A particular attraction of miktoarm stars is their versatility in achieving superior drug loading within their self-assembled structures. Advantages of dendrimers over linear polymers are that the former provide a platform for development of multivalent and multifunctional nanoconjugates, in addition to their ability to accommodate a large number of molecules inside, or at their surfaces.