Acetalated dextran (Ac-Dex) is a promising pH-sensitive biocompatible and biodegradable polymer for nanomedicine applications. In this work, Ac-Dex nanoparticles were synthesized by two different solvent evaporation methods, the single nanoemulsion and the double nanoemulsion. The Ac-Dex particles were characterized by scanning electron microscopy and the synthesis of highly homogeneous spherical particles was verified. Then, an optical fiber sensor based on quasi-elastic light scattering and comprised of only single-mode optical fibers and standard telecommunication devices showed sensitivity regarding the nanoparticles concentrations and was used for monitoring their degradation over 12 h under pH and temperature conditions of cancerous tissues. The results revealed a well-controlled degradation pattern, corroborating the suitability of the modified polymer to the release of active compounds in a sustainable manner and also demonstrating the applicability of the sensor for the in situ evaluation of the degradation.