Electrically conductive and functional polymeric nanoparticles have significant potential in biomedical applications such as in sensing and stimulation. Polymeric core-shell particles are usually prepared either through a multiple-step process or by the design of amphiphilic macromolecules. Here we report a simple one-step and one-pot emulsion polymerization method to synthesize the core-shell structured electrically conducting polymer particles based on the difference in comonomer reactivity. The morphology and the surface and bulk chemistry of poly(pyrrole-co-(1-(2-carboxyethyl)pyrrole)) (PPy-co-PPyCOOH) particles formed at different reaction times were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA) and total elemental analysis. The particles were found to be formed by a shell composed of the less conductive but functional PPyCOOH homopolymer, and a core made of the PPy dominated PPy-co-PPyCOOH copolymer of high conductivity. Human serum albumin antibody (anti-HSA) as a model molecule was covalently immobilized onto the particle surface and proven to be reactive to HSA. A five-step schema based on a novel reactivity-driven mechanism was proposed to explain the formation of the core-shell structure. This new strategy therefore provides a simple and general route to prepare core-shell conductive particles with a functional surface, based on the reactivity of comonomers.