The accurate sensing of local temperatures and/or the in situ sensing of oxygen are very important diagnostic tools for biomedical applications such as cancer and inflammation diseases. The goal of this project is to create a highly sensitive luminescence biosensor for dual thermometry and oxygen sensing operating in the physiological range (25 –50 °C). This will be accomplished through systematic Ag2S@Ln-COFs/CTFs core–shell particles design and synthesis. Core–shell particles compose of Ag2S nanoparticles core and covalent organic frameworks (COFs) shell with immobilized luminescent Ln3+ complexes. Ag2S NPs are very sensitive toward temperature change specifically in the relevant temperature range for biological applications. These NPs can be excited in the biological window I and they emit luminescence within the biological window II/III (near-infrared). In parallel, the Ln-COF shell can also act as an oxygen sensor that is excited in the UV and emits visible light. The COF shells will enhance the stability and biocompatibility of Ag2S NPs, provide anchoring points and antenna effect for lanthanides and enable temperature and oxygen probe in one multifunctional material. This allows simultaneous temperature and oxygen sensing with very well distinct emission with no mutual interfering. Furthermore, in vitro studies on human cells will be carried out in order to prove non toxicity for real biomedical applications.