A simple strategy is developed to prepare eccentrically or homogeneously loaded nanoparticles (NPs) using poly (DL-lactide-co-glycolide) (PLGA) as the encapsulation matrix in the presence of different amounts of polyvinyl alcohol (PVA) as the emulsifier. Using 2,3-bis(4-(phenyl(4-(1,2,2-triphenylvinyl)-phenyl)amino)-phenyl)-fumaronitrile (TPETPAFN), a fluorogen with aggregation-induced emission (AIE) characteristics, as an example, the eccentrically loaded PLGA NPs show increased fluorescence quantum yields (QYs) as compared to the homogeneously loaded ones. Field emission transmission electron microscopy and fluorescence lifetime measurements reveal that the higher QY of the eccentrically loaded NPs is due to the more compact aggregation of AIE fluorogens that restricts intramolecular rotations of phenyl rings, which is able to more effectively block the non-radiative decay pathways. The eccentrically loaded NPs show far red/near infrared emission with a high fluorescence QY of 34% in aqueous media. In addition, by using poly([lactide-co-glycolide]-b-folate [ethylene glycol]) (PLGA-PEG-folate) as the co-encapsulation matrix, the obtained NPs are born with surface folic acid groups, which are successfully applied for targeted cellular imaging with good photostability and low cytotoxicity. Moreover, the developed strategy is also demonstrated for inorganic-component eccentrically or homogeneously loaded PLGA NPs, which facilitates the synthesis of polymer NPs with controlled internal architectures.