Native nanodiamonds have the tendency to aggregate under physiological conditions, complicating their application to biological media. In fact, practical strategies to modify their surface with the aid of chemical synthesis, ensure biocompatibility and eventually permit their conjugation to biomolecules are very much needed. Indeed, synthetic approaches for the functionalization of nanodiamonds are currently under active investigation. At the present stage of their development, however, these strategies have yet to deliver effective protocols for the preparation of water-soluble nanodiamonds with optimal photophysical properties, lack of any tendency to aggregate and appropriate functionalities for bioconjugation. Only after overcoming these stringent limitations will nanodiamonds become valuable alternatives to organic dyes and quantum dots for bioimaging applications. The goal of this research project is the development of valuable luminescent probes for biomedical applications based on the unique properties of nanodiamonds. In particular, these studies will lead to the identification of optimal experimental protocols for the attachment of hydrophilic chains to the surface of preformed nanodiamonds and the conjugation of the resulting nanostructures to biomolecules. The passivating hydrophilic shell is designed to ensure aqueous solubility and prevent aggregation under physiological conditions, while preserving the characteristic photobleaching resistance and nontoxic character of the carbon-based core. Thus, the proposed nanoscaled constructs are expected to overcome the main limitations associated with organic dyes (photobleaching) and quantum dots (toxicity), in the context of fluorescence imaging applications, and offer the opportunity to visualize live cells for prolonged periods of time. Hence, these fundamental studies at the interface of chemical synthesis and nanostructured materials can provide useful analytical tools for the investigation of biological specimens and, ultimately, have a significant impact on biomedical research. The EAPSI project was focused on two types of luminescent nanoparticles: luminescent nanodiamonds (LND) and upconversion nanophosphors (UCNP). LND features extremely bright color centers that form very attractive base for magnetometry and biomedical applications. Due to the carbon nature of LND, its acid-treated surface contains a variety of oxygen-containing groups, including carboxyl groups (Figure 1). As such, LND provides suitable interface for covalent attachment of biomolecules, although the low percentage of the carboxyl groups, estimated at 7% of the total amount of functional groups, makes this attachment sparse and poorly controllable. The other type of nanomaterials, UCNP, is very attractive for background-free imaging of biomolecules, where the cell/tissue background autofluorescence suppression is primarily achieved by using an infrared excitation source, while detecting the UCNP emission in the visible spectral range, where no autofluorescence is excited by cells/tissue. The recent breakthrough in the synthesis of highly efficient UCNP has offered a range of small-size bright nanoparticles, and their promise for biomedical applications has been demonstrated. However, the as-synthesized surface moieties are hydrophobic, which are incompatible with biomolecular environment. Based on my proposed project, an interesting approach to modify LND and UCNP surfaces to render them hydrophilic and biocompatible was presented. In brief, the use of amphiphilic polymers featuring both hydrophobic and hydrophilic terminals, allows saturation of the hydrophobic moieties of e.g. UCNP, and converting them to hydrophilic moieties. The application of the amphiphilic polymer to both types of nanomaterials showed some changes in their aqueous colloidal properties: UCNP hydrophobic particles, originally immiscible in water were stabilized after addition of the amphiphilic polymer. Although the aqueous stability was limited to several days, the achieved short-term stability may allow performing bioconjugation reactions. Transmission electron microscopy observations in combination with the dynamic light scattering showed negligible particle size increase, which indicated that no dense polymer coating was formed on the UCNP surface, whereas the sparse polymer attachment might account for the improved water dispersity of the modified nanophosphors. In addition, I performed surface-modification reactions where the weakly attached UCNP surface groups were replaced by strong-binding mercaptopropionic acid groups. The colloidal precipitation occurred as expected but due after a few days, the nanoparticles showed to not be stable in water. However, the amphiphilic coating of LNDs showed more tangible results of the increased nanoparticle size, where the size increase of about 15 nm can be explained by the polymer thickness improving aqueous stability. I also carried out several analytical testing of the modified surface functional groups, using, in particular, Fourier transform infrared spectroscopy. It was inconclusive due to the limited resolution of the available instrument. In summary, during my short stay at Macquarie University, I performed several reactions using an amphiphilic polymer and other chemical procedures reported in literature, to find a chemical pathway to stabilize luminescent NDs and UCNP particles in water, and in physiological buffers to enable bioconjugation reactions. I was able to demonstrate that the amphiphilic polymer coating had some improvement on the colloidal stability of both LND and UCNP suspensions. If successful, this chemical pathway has potential to dress the existing lacuna in reliable surface modification of nanoparticles and enable their bioconjugation for cell delivery and imaging applications.