pH-sensitive polymers can be defined as polyelectrolytes that include in their structure weak acidic or basic groups that either accept or release protons in response to a change in the environmental pH. This work summarizes the design, synthesis, and potential applications of pH-responsive fluorescent copolymers in the biomedical field.This was achieved using atom transfer radical polymerization (ATRP) of tert-butyl acrylate using a CuBr/N,N,N 0 ,N 00 N 00 -pentamethyldiethylenetriamine catalyst system in conjunction with an alkyl bromide as the initiator. Well-defined macroinitiators based on poly(tert-butyl acrylate) with narrow molecular weight distributions were obtained by the addition of an appropriate solvent system in order to create a homogeneous catalytic system. The addition of n-butyl acrylate as a second building block in order to create well-defined poly(tert-butyl acrylate)-b-poly(n-butyl acrylate) block copolymers (PtBA-b-PnBA) followed by chemical modification of the block copolymers and functionalization with an appropriate fluorescent compound are the basis for the preparation of well-defined fluorescent pH-sensitive micelles. Thus, prepared water soluble nanosized pH-sensitive micelles consisting of hydrophobic poly(n-butyl acrylate) core and hydrophilic polyacrylic acid shell decorated with an appropriate fluorescent compound determined their potential applications of these systems in the field of biomedicine as biosensors, controlled drug delivery systems, and so on. In this respect, the cell viability and internalization of the polymer micelles were studied. K E Y W O R D S bioimaging, fluorescent nanosized micelles, personalized theranostic systems, pH-sensitive block copolymers 1 | INTRODUCTION These days, a wide range of compounds being developed are polymers, because of the variety of their chemical and physical properties and the possibility to be tailored towards many applications. In the last two decades, tremendous interest has been shown in polymeric materials that could reversibly or irreversibly change their physical and chemical properties under the influence of external stimuli, eg, pH, temperature, presence of specific ions, light radiation, mechanical forces, magnetic fields, electric fields, and bioactive molecules. 1 Among them, special attention is paid to the well-defined pH block copolymers, which at physiological pH (7.1-7.3) self-assemble into micellar structures and the acidification of the media lead to controlled micelle dissociation and triggered drug release. Several modern techniques can be applied for their synthesis as atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT), and stable free radical polymerization (SFRP). 2 These techniques are based on a reversible activation/deactivation cycle of
