The development of nanogels as nanoscale multifunctional polymer-based matrices for controlled drug and gene delivery purposes has been the subject of intense research during the last decades. Their use in biomedical field is related to the effect of their size on the interactions with living cells: only within a defined range nanoparticles could be subjected to active or passive cellular uptake. In this work we propose two methods to synthetize Rhodamine modified nanogels in order to produce nanostructures that could be traced during the cellular interactions and internalization and suitable as carrier for drugs or genes. We compared the obtained sizes and charges of both nanogels, underlining which one could be more useful for biological and therapeutic applications referring to the morphological and physico-chemical properties requested in accordance with medical needs. We also tested their cytocompatibility and their characteristic behavior as drug delivery vehicles. (C) 2016 Elsevier B.V. All rights reserved.