We report a versatile approach in which two highly efficient chemical reactions, multicomponent A 3 coupling and alkyne−azide click chemistry, are combined to construct dendrimer-based tools for applications in biology. Using a convergent approach, dendrons with desired architecture and an alkyne at the focal point are first assembled and then stitched together via multicomponent A 3 coupling reaction. The desired functional groups, including a stealth agent, imaging dye, and drug molecules, could be easily covalently linked to the surfaces of these hyperbranched macromolecules using alkyne−azide click chemistry. These A 3 -click dendrimers are noncytotoxic at concentrations as high as 1 μM and in fact reduce the toxicity of the drug. The dyecoated dendrimers specifically target and localize in lipid droplets. This unison methodology represents an attractive chemical strategy in exploiting the untapped potential of A 3 coupling and facilitating the development of nanodevices for imaging and drug delivery. D endrimers are hyperbranched macromolecules with a wide range of demonstrated applications in materials, catalysis, and biology. 1 Since their inception in the 1980s, the construction of these unique architectures has seen remarkable development. 2 A large variety of methodologies have been employed for their synthesis, and the inclusion of highly efficient click reactions, specifically copper(I)-catalyzed alkyne− azide (CuAAC) coupling, 3 is seen as a major breakthrough in dendrimer synthesis in the past decade. 4 This technique has been used in both convergent and divergent synthesis to grow the dendrimer generations, link dendrons together, and decorate their peripheries with a variety of functional groups. 5 The major advantages click reactions afford include high yields, byproduct free chemical transformations, and tolerance to a variety of solvents and functional groups. With the increasing potential for the use of dendrimers in a variety of applications, it will be advantageous to develop novel, efficient, and greener synthetic reactions comparable to click chemistry to build these macromolecular architectures. In this regard, highly efficient multicomponent reactions 6 that could combine three or more reaction partners in one pot and yield complex products from simple starting materials offer an exciting platform. A 3 coupling, first reported by Li's group, is one such example of a chemical reaction which is atom-economic and environmentally friendly. 7 A 3 coupling is a three-component catalytic coupling reaction of an alkyne, aldehyde, and amine to yield a propargyl amine. This three-component one-pot reaction combines the selectivity of reductive alkylation and the advantage of alkylation in a single step, under mild conditions. A wide variety of transition metal catalysts can be used to achieve A 3 coupling, including silver, gold, ruthenium/copper, copper, cobalt, iron, indium, and iridium. 8 We envision that A 3 coupling has all the desired features to be used as a synthetic tool for dendrimer b...