The attachment of specific ligands to the surfaces of nanoparticles is important for medical and biologic imaging. However, covalent modification of nanoparticles has inherent problems in reproducibility because of many factors such as temperature, pH, concentration, and reaction time. Thus, we developed a method for modifying nanoparticles by encapsulation with specific ligand-conjugated amphiphiles. Methods: We synthesized special amphiphiles with a hydrophilic head and a long single-alkyl chain, such as arginine-glycine-aspartic acid-C 18 , mannose-C 18 , lactose-C 18 , and 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid-C 18 . And then we produced stable quantum dots (QDs) encapsulated with polysorbate 60 (a branched polyethylene glycol head with a C 18 tail) and the synthesized special amphiphiles. The prepared encapsulated QDs were subject to in vitro and in vivo animal biodistribution studies and small-animal PET studies to confirm their specific binding. Results: The encapsulated QDs could specifically bind to target cells in vitro and in vivo and could be labeled with 68 Ga (a positron emitter) easily and with high efficiency. Conclusion: The nanoparticles encapsulated with special amphiphiles could provide a straightforward and novel imaging solution with multimodality and multispecificity.