In this study, a new imaging mesoporous nanoparticle is reported with exceptionally efficient and stable fluorescence emission, which was constructed by embedding and stabilizing quantum dots (QDs) of different sizes into porous nanobeads, following a lipid-PEG 2000-COOH coating which was further encoded with cRGD targeting peptide through biotin-streptavidin bridges. The mesopores had ∼10 nm diameter, were chemically modified, and facilitated internalization and stabilization of the QDs within the nanobeads upon the preparation protocol. Their outstanding optical contrasts render the highly fluorescent QDs as ideal fluorophores for wavelength-and-intensity multiplex color coding. The QDs tagged nanobeads showed optically strong and chemically stable imaging capability, both in vitro and in vivo, indicating powerful contrast modality among other alternatives. The cRGD-encoded lipid coated QDs tagged nanobeads (cRGD-encoded LQNBs) exhibited significantly increased α vβ 3-expressing cell targeting toward MCF-7 breast cancer cells over the α vβ 3-low expressing in HeLa cervix cancer cells, as confirmed by confocal laser scanning microscopy and flow cytometry. In MCF-7 xenograft nude mice, the cRGD-encoded LQNBs revealed prolonged accumulation time at the tumor site. In addition, the QNBs also demonstrated relatively high cell viability as compared to 3-mercaptopropionic acid (MPA)-functionalized QDs, indicating a successful design of highly-cytocompatible nanoparticulate platform capable of providing cell-specific targeting and nano-imaging modalities for biomedical applications.