Described is a versatile surface modification approach to, for example, modularly and orthogonally functionalize nanoparticles (NPs) such as, for example, PEGylated nanoparticles, ith various types of different functional ligands (functional groups) on the NP surface. It enables the synthesis of, for example, penta-functional PEGylated nanoparticles integrating a variety of properties into a single NP, e.g., fluorescence detection, specific cell targeting, radioisotope chelating/labeling, ratiometric pH sensing, and drug delivery, while the overall NP size remains, for example, below 10 nm.