A unique architecture of an engineered amphiphilic chemotherapeutic homopolymer enables fluorescence-assisted intracellular tracking and pH responsive drug delivery

Tracking of non-fluorescent drug after internalization is one of the major challenges. Herein, we developed homopolymer system where fluorescent probe and non-fluorescent drug are attached with similar pH-responsive linker. Alkylating agent drugs chlorambucil and fluorophore 1-pyrenebutyric acid were used as model molecules. Monomethyl poly(ethylene glycol) (mPeg-OH) was used for water solubility. Diacetylene moiety is well known for its cyclopolymerization. Towards this, <b>DIOL</b> containing diacetylene moiety was synthesized and selectively, one of the -OH group of <b>DIOL</b> was attached to water soluble moiety, whereas another -OH group was attached to free carboxylic acid-functionalized moiety containing chlorambucil and 1-pyrenebutyric acid, resulting in macromonomer <b>MPPDC</b>. Further, <b>MPPDC</b> was polymerized by Hoveyda Grubbs’ second generation (HG2) catalyst to get our final amphiphilic polymer <b>PMPPDC</b>. All the molecules were characterized carefully by different analytical techniques. Size and morphology were studied using dynamic light scattering (DLS) and transmission electron microscope (TEM), respectively, followed by release study at different pH. Cell viability and internalization studies were carried out with HeLa and MCF 7 cell lines. <b>PMPPDC</b> showed good cell growth inhibition in both cell lines. Similarly, increase in internalization was observed with increase in concentration of polymer <b>PMPPDC</b> in epifluorescence image.