Compositions are provided comprising water-stable semi-conductor nanoplatelets encapsulated in a hydrophilic coating further comprising lipids and lipoproteins. Uses include biomolecular imaging and sensing, and methods of making comprise: colloidal synthesis of CdSe core NPLs; layer-by-layer growth of a CdS shell; and encapsulation of CdSe/CdScore/shell NPLs in lipid and lipoprotein components through an evaporation-encapsulation using zwitterionic phospholipids, detergents, and amphipathic membrane scaffold proteins.